Haemodynamic definitions and updated clinical classification of pulmonary hypertension

Haemodynamic definitions and updated clinical classification of pulmonary hypertension Gérald Simonneau David Montani David S. Celermajer Christopher P. Denton Michael Α. Gatzoulis Michael J. Krowka Paul Williams Rogério Souza

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Haemodynamic definitions and updated clinical classification of pulmonary hypertension 2018 European Respiratory Journal 10.1183/13993003.01913-2018 simonneau2018-haemodynamic-definitions-and-updat simonneau2018-haemodynamic-definitions-and-updat.txt, the project's staged copy 885001ad1a2e65792ba23d13ce08e0f71dfc2a1f cc-by-nc clinical medicine

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them A DIAGNOSTIC THRESHOLD THAT DEFINED A DISEASE FOR 45 YEARS, LOWERED - pulmonary hypertension moves from mPAP >=25 mmHg, set at the 1st World Symposium in 1973 and called arbitrary in that meeting's own report, to >20 mmHg, the 97.5th percentile of 1187 normal subjects Quotation withheld because this record is not cleared for redistribution. whether pulmonary hypertension and pre-capillary pulmonary hypertension should be redefined, whether exercise PH should be brought back into the definition, and what the clinical classification should contain Quotation withheld because this record is not cleared for redistribution. a haemodynamic definition of pre-capillary PH with three simultaneous conditions - mPAP >20 mmHg, PAWP <=15 mmHg, PVR >=3 WU - a refusal to reintroduce exercise PH, and a simplified clinical classification with two new group 1 subgroups and two demotions out of group 5 Quotation withheld because this record is not cleared for redistribution. method Quotation withheld because this record is not cleared for redistribution. a disease whose presence is decided entirely by numbers from a catheter, where the numbers have no natural boundary and the boundary chosen changes who is ill Quotation withheld because this record is not cleared for redistribution. expert-consensus expert-consensus Quotation withheld because this record is not cleared for redistribution. THE OLD NUMBER WAS ARBITRARY AND THE 1973 MEETING SAID SO: `it was recognised that this upper limit of normal mPAP of 25 mmHg was somewhat empirical and arbitrarily defined. However, this conservative cut-off value allowed physicians to discriminate severe PH due to primary PH from other forms of PH ... characterised by a lower mPAP.` The threshold was chosen to separate the severe cases from everything else, not to mark where normal ends - a working boundary that became the definition of a disease for 45 years Quotation withheld because this record is not cleared for redistribution. AND IT WAS KEPT FOR ITS CONSEQUENCES, NOT ITS ACCURACY: `This definition REMAINED UNCHANGED during the subsequent WSPH meetings FROM 1998 TO 2013, at least in part to preclude potential overdiagnosis and overtreatment of PH.` Four international meetings declined to move a number they knew was arbitrary, because of what moving it would do. A definition held in place by its downstream effects is the cleanest instance of this in the corpus Quotation withheld because this record is not cleared for redistribution. AND THE NEW NUMBER WAS ALREADY IN THE 1961 REPORT: `In 1961, a report of the World Health Organization (WHO) Expert Committee on Chronic Cor Pulmonale mentioned clearly that the mean pulmonary arterial pressure does not normally exceed 15 mmHg ... and that the value was little affected by age AND NEVER EXCEEDED 20 mmHg.` The 2018 threshold is 20 mmHg. The evidence for the new boundary is 57 years older than the boundary it replaces, and the paper cites it as its first reference Quotation withheld because this record is not cleared for redistribution. AND THE NEW ONE IS A PERCENTILE: from `1187 normal subjects from 47 studies`, `mPAP at rest was 14.0+/-3.3 mmHg`, so `two standard deviations would suggest mPAP >20 mmHg as above the upper limit of normal ( i.e. above the 97.5th percentile). This definition is, therefore, no longer arbitrary, but based on a scientific approach.` The replacement for an arbitrary cut is a distributional convention - mean plus two standard deviations is a choice about how much of a normal population to call abnormal, and 2.5% is as much a convention as 25 mmHg was Quotation withheld because this record is not cleared for redistribution. AND THE COMPANION CRITERION IS ADMITTED TO BE ARBITRARY, FOUR PARAGRAPHS LATER: `This cut-off value of PVR >=3 WU is also quite arbitrary since some recent data suggest that PVR >2 WU could be also considered abnormal. In this sense, the use of a cut-off value of PVR >=3 WU IS CONSERVATIVE.` One definition, two thresholds: one de-arbitrarised by a percentile and one defended as arbitrary and conservative, and the same document says both Quotation withheld because this record is not cleared for redistribution. AND A NUMBER ALONE IS DECLARED INSUFFICIENT TO NAME A DISEASE: `Whatever the mPAP cut-off value considered for defining PH (>=25 or >20 mmHg), it is important to emphasise that this value used in isolation cannot characterise A clinical condition and does not define the pathological process per se.` The pressure can be raised by cardiac output, by a shunt, by wedge pressure or by blood viscosity - so the definition needs a second measurement to say WHERE the resistance is Quotation withheld because this record is not cleared for redistribution. AND THE PATIENTS ADDED BY THE CHANGE HAVE NO EVIDENCE BASE: `a change in the haemodynamic definition of PH due to PVDs does not imply treating these additional patients, but highlights the importance of close monitoring in this population. Prospective trials are required to determine whether this PH population might benefit from specific management.` A diagnosis is extended to people for whom no treatment is indicated and none has been tested - stated plainly, in the section that makes the change Quotation withheld because this record is not cleared for redistribution. AND THE EVIDENCE FOR MOVING IT IS THAT THE EXCLUDED BAND ALREADY BEHAVES LIKE THE DISEASE: of 38 systemic sclerosis patients with mPAP 21-24 mmHg re-catheterised, `16 of these (42%) developed overt PH`, and `Patients with so-called BORDERLINE mPAP at diagnosis were more likely to develop overt PAH than patients with mPAP <=20 mmHg (HR 3.7)`. In a 547-patient Austrian cohort, `both borderline PH and manifest PH were significantly associated with poor survival` (HR 2.37 and 5.05). The band between the old threshold and the new one was never healthy; it was outside the definition Quotation withheld because this record is not cleared for redistribution. AND A DEFINITION REMOVED IN 2008 WAS NOT RESTORED, FOR A MEASUREMENT REASON: `In 2004, PH was defined as resting mPAP >25 mmHg or exercise mPAP >30 mmHg. At the 4th WSPH in 2008, however, the `EXERCISE` part of the definition was removed.` Revisited in 2018 and refused again - `too many uncertainties persist to allow the reintroduction of a clinically useful definition of exercise PH` - because `it was impossible to distinguish LHD from PVD patients with confidence` and the measurement is `impractical as a clinical routine`. A criterion refused on the grounds that it cannot be measured, not that it is untrue Quotation withheld because this record is not cleared for redistribution. AND ONE WHOLE CLASS IS DEFINED BY WHAT IS NOT KNOWN ABOUT ITS MEMBERS: `the concept supporting the classification of a clinical condition ... into group 5 is, again, the lack of robust data allowing a definite recognition of predominant pathophysiological mechanisms, or describing the histopathological findings or yet, describing management strategies.` Group 5 was `disorders directly affecting the pulmonary vasculature` in 1998 and `MISCELLANEOUS` in 2003. Membership is an epistemic state, not a property of the disease - a paper leaves group 5 when the literature improves, not when the patient changes Quotation withheld because this record is not cleared for redistribution. AND TWO MEMBERS WERE DEMOTED FROM CONDITIONS TO RISK FACTORS: splenectomy, because `no other particular phenotype or change in clinical behaviour has been associated with [it], suggesting that it should be better considered as A risk factor for PH instead of A PARTICULAR CONDITION deserving a specific classification`; and thyroid disorders, `IT WAS A CONSENSUS TO WITHDRAW [them] from the classification as A SPECIFIC ENTITY and better discuss their role as risk factors`. The test for being a class rather than a correlate is whether membership predicts anything else Quotation withheld because this record is not cleared for redistribution. AND THE BAR FOR MOVING ANYTHING ELSE IS STATED: `We propose that changes be made only after the generation of robust data to support such reclassification.` A classification that names its own amendment rule - compare the same task force moving two entries out on exactly that ground in the paragraphs above Quotation withheld because this record is not cleared for redistribution. THE STRONGEST SENTENCE AGAINST THE PAPER IS THE PAPER'S OWN: `This cut-off value of PVR >=3 WU is also quite arbitrary.` The abstract sells the mPAP change as `no longer arbitrary, but based on a scientific approach`; the definition it proposes requires BOTH numbers, and only one of them has been de-arbitrarised. A definition is no more principled than its least principled conjunct Quotation withheld because this record is not cleared for redistribution. AND `no longer arbitrary` MEANS `A DIFFERENT CONVENTION`: mean plus two standard deviations in `1187 normal subjects from 47 studies` is a rule about how much of a healthy population to place outside normal - `above the 97.5th percentile`. It is reproducible, auditable and far better than a show of hands, and it is still a choice of tail. The paper does not claim 20 mmHg is where the pathology starts; it claims it is where the normal distribution ends Quotation withheld because this record is not cleared for redistribution. AND THE NEW DIAGNOSIS COMES WITH NOTHING TO DO ABOUT IT: `Prospective trials are required to determine whether this PH population might benefit from specific management.` The task force is explicit that widening the definition `does not imply treating these additional patients` - which is the right disclosure, and leaves every patient newly inside the boundary with a disease name and a monitoring plan Quotation withheld because this record is not cleared for redistribution. AND THE OVERDIAGNOSIS ARGUMENT IS ANSWERED BY REDIRECTING IT: `For many years, the diagnosis of PH was based on an arbitrary value ... probably because of understandable concern about overdiagnosis and overtreatment. Actually, the main cause of overdiagnosis ... is the failure to confirm the diagnosis by RHC.` The reply is that overdiagnosis comes from skipping the catheter rather than from where the line sits - true, and it does not measure how many more people the new line admits, which this paper does not estimate Quotation withheld because this record is not cleared for redistribution. AND THE DISCLOSURES ARE DENSE AND UNIFORM: `Quotation withheld` Seven of the eight authors file a comparable statement, most naming Actelion. Every one is declared, none is hidden, and a task force that widens a disease boundary is advised by people paid by the manufacturers of its treatments - which is a fact about the field's structure, not an allegation about this paper Quotation withheld because this record is not cleared for redistribution. requiring PAWP <=15 mmHg and PVR >=3 WU alongside the pressure, so that a raised mPAP counts only when it is resistance eliminates: calling high cardiac output, a left-to-right shunt, left heart disease or hyperviscosity 'pulmonary vascular disease' · outcome: held Quotation withheld because this record is not cleared for redistribution. refusing to reintroduce exercise PH into the definition eliminates: a criterion that separates the healthy from the ill but cannot say which disease, and that is 'impractical as a clinical routine' · outcome: held Quotation withheld because this record is not cleared for redistribution. stating that the new definition 'does not imply treating these additional patients' eliminates: reading a widened diagnostic boundary as a widened treatment indication · outcome: partial Quotation withheld because this record is not cleared for redistribution. requiring robust data before any further reclassification, and applying that rule immediately by demoting splenectomy and thyroid disorders out of group 5 eliminates: a classification that grows by plausibility · outcome: held Quotation withheld because this record is not cleared for redistribution. pulmonary hypertension (PH) pulmonary hypertension (PH) Quotation withheld because this record is not cleared for redistribution. mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest Quotation withheld because this record is not cleared for redistribution. Pre-capillary PH Pre-capillary PH Quotation withheld because this record is not cleared for redistribution. mPAP >20 mmHg, PAWP ≤15 mmHg and PVR ≥3 WU mPAP >20 mmHg, PAWP ≤15 mmHg and PVR ≥3 WU Quotation withheld because this record is not cleared for redistribution. PAP elevation PAP elevation Quotation withheld because this record is not cleared for redistribution. increase in cardiac output increase in cardiac output Quotation withheld because this record is not cleared for redistribution. LHD LHD Quotation withheld because this record is not cleared for redistribution. PVD PVD Quotation withheld because this record is not cleared for redistribution. PAH PAH Quotation withheld because this record is not cleared for redistribution. PVOD/PCH PVOD/PCH Quotation withheld because this record is not cleared for redistribution. group 5 group 5 Quotation withheld because this record is not cleared for redistribution. forms of PH with unclear and/or multifactorial mechanisms forms of PH with unclear and/or multifactorial mechanisms Quotation withheld because this record is not cleared for redistribution. PAH with vasoreactivity PAH with vasoreactivity Quotation withheld because this record is not cleared for redistribution. IPAH IPAH Quotation withheld because this record is not cleared for redistribution. borderline mPAP borderline mPAP Quotation withheld because this record is not cleared for redistribution. mPAP ≤20 mmHg mPAP ≤20 mmHg Quotation withheld because this record is not cleared for redistribution. Definite association Definite association Quotation withheld because this record is not cleared for redistribution. drugs with data based on outbreaks, epidemiological case–control studies or large multicentre series drugs with data based on outbreaks, epidemiological case–control studies or large multicentre series Quotation withheld because this record is not cleared for redistribution. `pulmonary hypertension`, 1973-2018 sense - `mPAP >=25 mmHg at rest, measured by right heart catheterisation`, a value the defining meeting called `somewhat empirical and arbitrarily defined` Quotation withheld because this record is not cleared for redistribution. `pre-capillary PH`, 2018 sense - THREE conditions at once: `mPAP >20 mmHg, PAWP <=15 mmHg and PVR >=3 WU`. The second and third exist to say that the raised pressure is resistance and not flow or wedge Quotation withheld because this record is not cleared for redistribution. `borderline PH` - mPAP 21-24 mmHg: the band between the old threshold and the new one, which had a name while it was outside the definition Quotation withheld because this record is not cleared for redistribution. `exercise PH` - part of the definition in 2004 (`exercise mPAP >30 mmHg`), removed in 2008, reconsidered and refused in 2018 because exercise PAWP cannot be measured reliably enough to tell left heart disease from pulmonary vascular disease Quotation withheld because this record is not cleared for redistribution. `group 5` - PH `with unclear and/or multifactorial mechanisms`; previously `disorders directly affecting the pulmonary vasculature` (1998) and `MISCELLANEOUS` (2003). The class of conditions we do not yet understand Quotation withheld because this record is not cleared for redistribution. `definite` vs `possible` drug association - definite means `data based on outbreaks, epidemiological case-control studies or large multicentre series`; possible means `multiple case series`. A membership grade defined by STUDY DESIGN Quotation withheld because this record is not cleared for redistribution. extends → the 1st WSPH definition of 1973 (mPAP >=25 mmHg) and its restatements at every WSPH from 1998 to 2013, which this task force replaces Quotation withheld because this record is not cleared for redistribution. extends → Kovacs et al.'s pooled analysis of 1187 normal subjects from 47 right-heart-catheterisation studies, from which the new threshold is derived Quotation withheld because this record is not cleared for redistribution. critiques → the use of a single pressure value as a diagnosis - 'this value used in isolation cannot characterise a clinical condition and does not define the pathological process per se' Quotation withheld because this record is not cleared for redistribution. critiques → the 2004 exercise criterion ('exercise mPAP >30 mmHg'), removed in 2008 and refused readmission here because exercise PAWP cannot distinguish left heart disease from pulmonary vascular disease Quotation withheld because this record is not cleared for redistribution. pulmonary hypertension (PH) —operationalised-as→ mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest pulmonary hypertension (PH) mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest the relation itself is separately evidenced · strength of the relation: 0.95 · note: '(PH) HAS BEEN…' The adverb is the authors' own, in the first sentence of the abstract - and the 1973 report is quoted later saying the same thing about itself · the relation stated: from 1973 to this paper, having the disease meant having a catheter reading at or above 25 mmHg at rest - a number the defining meeting recorded as arbitrary Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says PH was ARBITRARILY defined this way and that the definition is now revised to >20 mmHg; superseded. Quotation withheld because this record is not cleared for redistribution. Pre-capillary PH —operationalised-as→ mPAP >20 mmHg, PAWP ≤15 mmHg and PVR ≥3 WU Pre-capillary PH mPAP >20 mmHg, PAWP ≤15 mmHg and PVR ≥3 WU the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'Pre-capillary PH is best…' Lowering one threshold forced two more into the definition - because 'THIS VALUE USED…', and the further down the pressure scale you go the more true that is · the relation stated: the 2018 definition is a conjunction of three catheter measurements, two of them present only to prove that the raised pressure is resistance rather than flow Quotation withheld because this record is not cleared for redistribution. increase in cardiac output —causes→ PAP elevation increase in cardiac output PAP elevation the relation itself is separately evidenced · strength of the relation: 0.9 · note: 'PAP ELEVATION…' The edge runs from the cause to the reading, against the order of the sentence. This is the argument that forced PVR into the definition: a measurement with many causes cannot, alone, be a diagnosis · the relation stated: raised pulmonary pressure has several unrelated causes - high cardiac output, a shunt, raised wedge pressure, hyperviscosity - only one of which is vascular disease Quotation withheld because this record is not cleared for redistribution. forms of PH with unclear and/or multifactorial mechanisms —part-of→ group 5 forms of PH with unclear and/or multifactorial mechanisms group 5 the relation itself is separately evidenced · strength of the relation: 0.9 · note: `Since the basis of our classification system was established in 1998, group 5 has passed through significant changes. Initially describing `disorders directly affecting the pulmonary vasculature`, then named `MISCELLANEOUS` during the 3rd WSPH in 2003, and finally reaching its current presentation, this group includes forms of PH with unclear and/or multifactorial mechanisms.` The renaming across three meetings has no edge type in schema 0.3 - `renamed-across-fields` is false here, because it is one field renaming its own category over time. Filed in the open questions rather than forced into the nearest type · the relation stated: group 5 contains the conditions for which no predominant mechanism has been established - membership is a statement about the literature, not the patient Quotation withheld because this record is not cleared for redistribution. PAH with vasoreactivity —distinct-from→ IPAH PAH with vasoreactivity IPAH the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'PAH with vasoreactivity was…' The subgroup is created because 'These results…'. A class created by treatment response and then corroborated molecularly - the reverse of the usual order, and the paper is candid that 'Pathophysiology of…' · the relation stated: long-term calcium-channel-blocker responders differ from idiopathic PAH in blood signature and gene variants as well as in prognosis, which is the case for making them a subgroup Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span reports what Hemnes and co-workers showed. Quotation withheld because this record is not cleared for redistribution. borderline mPAP —contrasted-with→ mPAP ≤20 mmHg borderline mPAP mPAP ≤20 mmHg the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'PATIENTS WITH SO-CALLED…' The comparison is between two bands of one continuous variable, and it is the only kind of evidence that can move a threshold: show that the excluded side already behaves like the included one · the relation stated: patients in the 21-24 mmHg band progressed to overt disease far more often than those below 20 mmHg - the empirical case that the old boundary was in the wrong place Quotation withheld because this record is not cleared for redistribution. drugs with data based on outbreaks, epidemiological case–control studies or large multicentre series —part-of→ Definite association drugs with data based on outbreaks, epidemiological case–control studies or large multicentre series Definite association the relation itself is separately evidenced · strength of the relation: 0.9 · note: `'DEFINITE ASSOCIATION' INCLUDES DRUGS WITH DATA BASED ON OUTBREAKS, EPIDEMIOLOGICAL CASE-CONTROL STUDIES OR LARGE MULTICENTRE SERIES. 'POSSIBLE ASSOCIATION' is suggested by multiple case series or cases with drugs with similar mechanisms of action.` An evidential grade written into a classification - and note the asymmetry: mechanism similarity is enough for `possible` and never enough for `definite` · the relation stated: whether a drug is a definite or a possible cause of PAH is decided by the study design behind the association, not by the strength of the effect or a mechanism Quotation withheld because this record is not cleared for redistribution. A 45-YEAR-OLD DIAGNOSTIC THRESHOLD LOWERED: `PH has been ARBITRARILY DEFINED as mPAP >=25 mmHg` -> `mPAP >20 mmHg ... This definition is, therefore, no longer arbitrary, but based on a scientific approach` A 45-YEAR-OLD DIAGNOSTIC THRESHOLD LOWERED: `PH has been ARBITRARILY DEFINED as mPAP >=25 mmHg` -> `mPAP >20 mmHg ... This definition is, therefore, no longer arbitrary, but based on a scientific approach` Quotation withheld because this record is not cleared for redistribution. AND THE COMPANION CRITERION IS ADMITTED TO BE ARBITRARY IN THE SAME SECTION: `This cut-off value of PVR >=3 WU is also quite arbitrary ... In this sense, the use of a cut-off value of PVR >=3 WU IS CONSERVATIVE` AND THE COMPANION CRITERION IS ADMITTED TO BE ARBITRARY IN THE SAME SECTION: `This cut-off value of PVR >=3 WU is also quite arbitrary ... In this sense, the use of a cut-off value of PVR >=3 WU IS CONSERVATIVE` Quotation withheld because this record is not cleared for redistribution. AND THE DEFINITION WAS HELD IN PLACE BY ITS CONSEQUENCES: `This definition REMAINED UNCHANGED during the subsequent WSPH meetings from 1998 to 2013, at least in part to preclude potential overdiagnosis and overtreatment of PH` AND THE DEFINITION WAS HELD IN PLACE BY ITS CONSEQUENCES: `This definition REMAINED UNCHANGED during the subsequent WSPH meetings from 1998 to 2013, at least in part to preclude potential overdiagnosis and overtreatment of PH` Quotation withheld because this record is not cleared for redistribution. AND THE NEW NUMBER IS IN THE 1961 REPORT: WHO's Expert Committee said mPAP `does not normally exceed 15 mmHg ... and never exceeded 20 mmHg` - 57 years before the threshold moved to 20 AND THE NEW NUMBER IS IN THE 1961 REPORT: WHO's Expert Committee said mPAP `does not normally exceed 15 mmHg ... and never exceeded 20 mmHg` - 57 years before the threshold moved to 20 Quotation withheld because this record is not cleared for redistribution. the new definition does not imply treating the added patients; prospective trials must show whether they benefit the new definition does not imply treating the added patients; prospective trials must show whether they benefit Quotation withheld because this record is not cleared for redistribution. total pulmonary resistance separated controls from LHD or PVD patients but could not distinguish LHD from PVD with confidence total pulmonary resistance separated controls from LHD or PVD patients but could not distinguish LHD from PVD with confidence Quotation withheld because this record is not cleared for redistribution. group 5 membership rests on the lack of robust data identifying predominant pathophysiological mechanisms group 5 membership rests on the lack of robust data identifying predominant pathophysiological mechanisms Quotation withheld because this record is not cleared for redistribution. splenectomy is better considered a risk factor for PH than a condition deserving its own classification splenectomy is better considered a risk factor for PH than a condition deserving its own classification Quotation withheld because this record is not cleared for redistribution. AND A DISTINCTION WAS DISSOLVED INTO A SPECTRUM: `PAH and PVOD/PCH belong to a spectrum of PVDs rather than representing two clear-cut distinct entities` AND A DISTINCTION WAS DISSOLVED INTO A SPECTRUM: `PAH and PVOD/PCH belong to a spectrum of PVDs rather than representing two clear-cut distinct entities` Quotation withheld because this record is not cleared for redistribution. AND A MEMBERSHIP GRADE IS MADE OF STUDY DESIGNS: `Definite association` requires `outbreaks, epidemiological case-control studies or large multicentre series`; `POSSIBLE` accepts `multiple case series` or a similar mechanism AND A MEMBERSHIP GRADE IS MADE OF STUDY DESIGNS: `Definite association` requires `outbreaks, epidemiological case-control studies or large multicentre series`; `POSSIBLE` accepts `multiple case series` or a similar mechanism Quotation withheld because this record is not cleared for redistribution. `mPAP >=25 mmHg at rest, measured by right heart catheterisation` - `somewhat empirical and arbitrarily defined`, in the words of the meeting that set it pulmonary hypertension Quotation withheld because this record is not cleared for redistribution. `the concomitant presence of mPAP >20 mmHg, PAWP <=15 mmHg and PVR >=3 WU` - three readings, all from one catheter pre-capillary PH Quotation withheld because this record is not cleared for redistribution. `14.0+/-3.3 mmHg` in 1187 normal subjects, so `two standard deviations would suggest mPAP >20 mmHg ... above the 97.5th percentile` upper limit of normal mPAP Quotation withheld because this record is not cleared for redistribution. `a reduction of mPAP >=10 mmHg TO REACH an absolute value of mPAP <=40 mmHg with an increased or unchanged CO` - a change AND a level AND a third condition acute vasodilator response Quotation withheld because this record is not cleared for redistribution. `the lack of robust data allowing a definite recognition of predominant pathophysiological mechanisms` - a criterion about the literature group 5 Quotation withheld because this record is not cleared for redistribution. the 1973 value was `somewhat empirical and arbitrarily defined`; the new value is the 97.5th percentile of normal the threshold that defines the disease Quotation withheld because this record is not cleared for redistribution. `this value was independent of sex and ethnicity, and was only slightly influenced by age and posture` the normal reference distribution Quotation withheld because this record is not cleared for redistribution. defended as `CONSERVATIVE, suggesting the presence of a MANIFEST pre-capillary PH` the resistance criterion Quotation withheld because this record is not cleared for redistribution. `HR 3.7` against patients at mPAP <=20 mmHg; in a separate cohort, borderline PH carried `HR 2.37` for death against the lower-normal group progression from the band between the two thresholds Quotation withheld because this record is not cleared for redistribution. the exercise rule of thumb that replaced it is `>=3 mmHg per litre of CO` in disease against `>=1` in normal subjects the wedge-pressure ceiling and the exercise criterion Quotation withheld because this record is not cleared for redistribution. `Quotation withheld` 2.5% is a convention about how much of a healthy population to call abnormal. It is reproducible and auditable, which the 1973 number was not, and it is not a measurement of where disease begins mean plus two standard deviations, doing the work of a disease boundary Quotation withheld because this record is not cleared for redistribution. `HR 3.7` for progression from the 21-24 mmHg band, `HR 2.37` (95% CI 1.14-4.97) for death in borderline PH against lower-normal, `HR 5.05` for manifest PH. The middle band sits between the two in every table - which is what a threshold in the wrong place looks like hazard ratios as the argument for moving a threshold Quotation withheld because this record is not cleared for redistribution. `the group with mPAP 21-24 mmHg had a median PVR of 2.7 WU and 36% of these patients had PVR >3 WU` - so the conjunctive definition admits about a third of the band, not all of it. The second criterion is what keeps the change from being a straight reclassification of everyone above 20 mmHg 36% of the borderline band already meet the new resistance criterion Quotation withheld because this record is not cleared for redistribution. `PVR=(mPAP-PAWP)/CO` - a derived quantity, and the one that lets the definition say WHERE the pressure comes from. Its own threshold is `also quite arbitrary` pulmonary vascular resistance Quotation withheld because this record is not cleared for redistribution. the term that separates pre- from post-capillary PH, and the measurement whose unreliability during exercise killed the exercise criterion pulmonary arterial wedge pressure (PAWP) Quotation withheld because this record is not cleared for redistribution. the instrument the whole definition is made of - and, the paper argues, the real remedy for overdiagnosis: `the main cause of overdiagnosis ... is the failure to confirm the diagnosis by RHC` right heart catheterisation (RHC) Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1183/13993003.01913-2018.