Performance Under Pressure

FOR RELATED ARTICLE, SEE PAGE 781Pulmonary arterial hypertension (PAH) affects up to 10% of patients with systemic sclerosis (SSc) and is a leading cause morbidity mortality in this devastating disease.1Tyndall A.J. Bannert B. Vonk M. et al.Causes risk factors for death sclerosis: study from the EULAR Scleroderma Trials Research (EUSTAR) database.Ann Rheum Dis. 2010; 69: 1809-1815Crossref PubMed Scopus (788) Google Scholar,2Condliffe R. Howard L.S. Connective tissue disease-associated pulmonary hypertension.F1000Prime Rep. 2015; 7: 06Crossref (36) Scholar PAH SSc has an even worse prognosis than idiopathic PAH, targeted therapies are less effective.3Hurdman J. Condliffe Elliot C.A. al.ASPIRE registry: assessing Spectrum Pulmonary Identified at REferral centre.Eur Respir 2012; 39: 945-955Crossref (285) Scholar,4Ramjug S. Hussain N. Hurdman al.Idiopathic sclerosis-associated hypertension: comparison demographic, hemodynamic, MRI characteristics outcomes.Chest. 2017; 152: 92-102Abstract Full Text PDF (31) Efforts have been directed toward early diagnosis SSc, idea that starting treatment prior extensive vascular remodeling may slow or prevent right ventricular dysfunction, which primary determinant outcomes PAH.5Humbert Guignabert C. Bonnet al.Pathology pathobiology state art research perspectives.Eur 2019; 53Crossref (453) Scholar, 6Humbert Yaici A. de Groote P. al.Screening clinical long-term survival.Arthritis Rheum. 2011; 63: 3522-3530Crossref (243) 7Coghlan J.G. Denton C.P. Grunig E. al.Evidence-based detection DETECT study.Ann 2014; 73: 1340-1349Crossref (485) As shown by Hsu al,8Hsu Kokkonen-Simon K.M. Kirk J.A. al.Right myofilament functional differences humans versus hypertension.Circulation. 2018; 137: 2360-2370Crossref (64) mildly elevated pressures (PAPs) impaired myocardial sarcomere function compared vs suggesting dysfunction occurs disease be more profound SSc. Furthermore, recent studies reported impact on various states, including These findings led revisions diagnostic criteria lowering mean PAP threshold 20 mm Hg.9Maron B.A. Brittan E.L. Hess al.Pulmonary resistance retrospective cohort study.Lancet Med. 2020; 8: 873-884Abstract (40) 10Simonneau G. Montani D. Celermajer D.S. al.Haemodynamic definitions updated classification hypertension.Eur (1506) 11Maron Maddox T.M. al.Association borderline hospitalization large patient cohort: insights Veterans Affairs Clinical Assessment, Reporting, Tracking Program.Circulation. 2016; 133: 1240-1248Crossref (185) However, (PVR) also seems portend poor prognosis, but not yet incorporated into guidelines.12Xanthouli Jordan Milde phenotypes survival new definition hypertension.Ann 79: 370-378Crossref (34) Screening programs include different measures algorithms established many centers worldwide caring goal detecting earlier6Humbert Scholar,7Coghlan Scholar,13Weatherald Jevnikar Jais X. Savale L. Humbert sclerosis.Eur Rev. 28Crossref (32) Scholar; however, none designed detect (mPAP > Hg) PVR (PVR 2 Wood units), important impact. A potentially valuable tool earlier such as assess hemodynamics during exercise.4Ramjug 5Humbert 8Hsu 9Maron 12Xanthouli 13Weatherald 14Lau E.M. Chemla Godinas al.Loss distensibility exercise hemodynamic marker disease.Chest. 149: 353-361Abstract (42) 15Herve Lau Sitbon O. al.Criteria 46: 728-737Crossref (172) 16Kovacs Herve Barbera al.An official European Respiratory Society statement: haemodynamics exercise.Eur 50Crossref (142) 781 Exercise stresses vasculature progressively increasing cardiac output (CO) and, consequently, pressure augmenting load.17Naeije Chesler circulation exercise.Compr Physiol. 2: 711-741Crossref (116) Nature elegantly addressed vital challenge equipping sufficiently low high compliance accommodate entire maximal exercise.18Waxman A.B. physiology hypertension.Prog Cardiovasc 55: 172-179Crossref (29) Recruitment distension vessels lead decreased exercise17Naeije Scholar,19Johnson Jr., R.L. Hsia C.C. Functional recruitment capillaries.J Appl 1994; 76: 1405-1407Crossref (17) exact underlying mechanisms regulating these responses still unknown. adaptive overcome additional escalation related stretching lung volume characterized vasoconstriction artery smooth muscles, remodeling, endothelial cell proliferation20Voelkel N.F. Cool Pathology hypertension.Cardiol Clin. 2004; 22 (v): 343-351Abstract (46) rest. With exercise, increases further, most likely due insufficient distention diseased vessels.14Lau An abnormal response defined increase mPAP 30 Hg combined mPAP/CO (total resistance) 3 units peak exercise.15Herve Scholar,16Kovacs found associated dyspnea assessed using heart catheterization21Ho J.E. Zern E.K. E.S. al.Exercise predicts effort.J Am Coll Cardiol. 75: 17-26Crossref (33) distal chronic thromboembolic hypertension.22Hasler E.D. Muller-Mottet Furian al.Pressure-flow catheterization hypertension.Chest. 150: 57-67Abstract Patients fulfilling discussed similarly diagnosed according resting hemodynamics.23Stamm Saxer Lichtblau predict outcome 48: 1658-1667Crossref (41) In issue CHEST, Zeder al24Zeder K. Avian Bachmaier resistances sclerosis.Chest. 2021; 159: 781-790Abstract (6) further add growing body evidence emphasizing importance The authors show both total pressure-flow slopes were independent predictors mortality, whereas respective not. From physiological standpoint, plausible it hypothesized 50% 70% needs affected raise 25 Hg.25Austin Kawut S.M. Gladwin M.T. Abman S.H. NHLBI Workshop prevention diseases.Ann Thorac Soc. : S178-S185Crossref Thus, expected would necessarily affect load might unmask dysfunctional stages progression. observation inherently important, therefore, suggests routine assessment warranted population. larger question will whether subsequent vasodilators delay progression disease. Unfortunately, despite data efficacy initial combination therapy SSc-PAH,26Hassoun P.M. Zamanian R.T. Damico al.Ambrisentan tadalafil up-front scleroderma-associated hypertension.Am J Crit Care 192: 1102-1110Crossref (108) Scholar,27Coghlan Galie al.Initial ambrisentan connective (CTD-PAH): subgroup analysis AMBITION trial.Ann 1219-1227Crossref (109) date we limited initiating PAH-targeted suspected based improves outcomes.23Stamm Scholar,28Pan Z. Marra A.M. Benjamin al.Early randomized, controlled, double-blind, parallel group (EDITA study).Arthritis Res Ther. 21: 217Crossref (23) 29Kovacs Maier Aberer safe effective pressure.Arthritis 64: 1257-1262Crossref (63) 30Saggar Khanna Shapiro al.Brief report: effect exercise-induced prospective single-center, open-label pilot study.Arthritis 4072-4077Crossref (49) because currently approved humans, role remains unclear. Importantly, challenging defined, unlikely used current trials, time worsening, applicable practical Still, results support utility Their highlight need future investigations identify validate appropriate randomized trials Resistances Predict Long-Term Survival Systemic SclerosisCHESTVol. 159Issue 2PreviewPVR TPR slope, TPG/CO slope age-adjusted no increased pressure. Full-Text