Pulmonary hypertension and right heart failure clinical reference

Cardiology / Pulmonology

PulmHTN-RHF

mPAP >20 mmHg on RHC · WHO Groups 1–5 · classify before treating · Group 2 PH (LHD) is most common — PAH drugs worsen it · RHF = ↑afterload → RV dilation → D-sign → ↓LV CO · Super Compact

• Sx: progressive exertional dyspnea (years before diagnosis) · fatigue · exertional syncope (ominous — ↓CO augmentation; high-risk feature); RHF signs: JVD · HJR · pulsatile hepatomegaly · ascites · bilateral edema · RV S3 at LLSB; exam: loud P2 · RV heave · TR murmur (increases with inspiration) · cyanosis in severe disease; Raynaud/telangiectasia/skin thickening → SSc-PAH

• Neg: denies PCWP >15 mmHg on RHC (Group 2 LHD — most common PH; PAH-specific drugs increase pulmonary blood flow into a congested circuit → flash APE; NEVER give ERA/PDE5i without RHC confirming pre-capillary PH) · denies mismatched perfusion defects on V/Q + prior PE hx (CTEPH Group 4 — riociguat [Adempas] only approved Rx; PEA surgery potentially curative) · denies obstructive/restrictive pattern on PFTs + parenchymal disease on CT (Group 3 — treat lung disease + O2; PAH drugs not indicated)

• SHx: prior PE/DVT (CTEPH Group 4) · CTD (SSc — 8–12% lifetime PAH risk; annual echo screening) · HIV · portal HTN/cirrhosis (portopulmonary) · appetite suppressants/methamphetamines/dasatinib (Sprycel) · COPD/ILD severity · OSA · pregnancy (30–50% maternal mortality in WHO FC III–IV — contraindicated) · BMPR2 family hx

• Etiology: Group 1 PAH: idiopathic/heritable (BMPR2) · CTD (SSc) · HIV · portopulmonary · CHD (Eisenmenger) · drugs/toxins; Group 2 (most common): HFpEF/HFrEF/valvular (PCWP>15); Group 3: COPD/ILD/OSA/hypoxia; Group 4 CTEPH: chronic thromboembolic; Group 5: sarcoid/hemolytic anemia/metabolic

• RF: female sex · age 30–60 (iPAH) · SSc (highest CTD risk) · prior PE (CTEPH) · HIV · portal HTN · fenfluramine/amphetamines/dasatinib (Sprycel) · BMPR2 mutation carrier · COPD/ILD severity

• Data: echo TTE (TR velocity>3.4 m/s=high prob PH; RV:LV ratio>1.0; D-sign=RV pressure overload; pericardial effusion=poor prognosis; TAPSE<16=↓RV function; IVC>21mm+<50% collapse=↑RAP) · RHC gold standard (mPAP>20; PVR≥2 WU; PCWP≤15=pre-capillary Groups 1/3/4/5; PCWP>15=post-capillary Group 2; vasoreactivity test [inhaled NO]→positive=mPAP↓≥10 to<40+↑CO→CCB trial in ~10% iPAH) · V/Q scan (CTEPH: V/Q more sensitive than CT-PA for chronic clot; mismatched defects) · PFTs+DLCO (obstructive=Group 3 COPD; restrictive=ILD; ↓DLCO in PAH+ILD) · 6MWD (baseline+response; <300m=high risk) · BNP/NT-proBNP (RV strain; target↓>30% with treatment) · CTD serology (ANA+anti-Scl70+anti-centromere) · HIV · LFTs (portopulmonary)

• DDx: Group 2 LHD (PCWP>15; most common PH — treat LV; PAH drugs contraindicated) · CTEPH Group 4 (prior PE+V/Q defects — anticoag+riociguat [Adempas]+BPA/PEA) · COPD/ILD Group 3 (PFTs+CT — O2+treat lung) · Massive PE acute (acute onset+hemodynamic collapse — tPA+anticoag) · Tamponade (RV compression+effusion — pericardiocentesis) · Portopulmonary HTN (portal HTN+PAH physiology — Group 1; liver transplant if PAH mild)

• Home Meds: NEVER stop IV/SC prostacyclin (epoprostenol [Flolan]/treprostinil [Remodulin]) abruptly — rebound vasoconstriction → death within hours; continue ERA+PDE5i+diuretics+warfarin (Coumadin) if CTEPH; AVOID ACEi/ARB/BB in Group 1 PAH (↓SVR→shunting→syncope); AVOID NSAIDs; AVOID estrogen-containing OCP (↑VTE+↑PAH risk)

Plan

• RHC before any PAH therapy — classify Group first; PCWP≤15 + PVR≥2 WU = pre-capillary (Groups 1/3/4/5 → PAH drugs); PCWP>15 = post-capillary Group 2 (treat LV — NEVER PAH drugs); pulm HTN specialist Day 1

• Acute RHF management: O2 to SpO2>92% (hypoxia = potent pulm vasoconstrictor); judicious diuresis — furosemide (Lasix) 40–80 mg IV (target CVP 8–12; avoid over-diuresis → ↓RV preload → ↓CO); vasopressin (Pitressin) 0.03–0.04 units/min preferred pressor (↑SVR without ↑PVR); milrinone (Primacor) 0.1–0.375 mcg/kg/min (↓PVR+↑RV inotropy); inhaled NO 10–40 ppm (selective pulm vasodilator; requires delivery system); AVOID excessive IVF (worsens D-sign+↓LV filling); AVOID intubation if possible (PPV ↑PVR → ↑RV afterload → hemodynamic collapse) | AF in RHF = cardiovert urgently — loss of atrial kick in pressure-overloaded RV = rapid hemodynamic collapse

• Group 1 PAH targeted therapy (with PAH center): initial combination (AMBITION 2015: ambrisentan [Letairis]+tadalafil [Adcirca] ↓clinical failure 50% vs monotherapy; NNT~5 — now standard first-line for WHO FC II–III):

• ERA: macitentan (Opsumit) 10 mg PO daily (SERAPHIN: ↓morbidity/mortality 45%; preferred long-term; monthly pregnancy test) · ambrisentan (Letairis) 5→10 mg PO daily · bosentan (Tracleer) 62.5→125 mg PO BID (monthly LFTs)

• PDE5i: tadalafil (Adcirca) 40 mg PO daily (preferred — once daily) · sildenafil (Revatio) 20 mg PO TID; CANNOT combine PDE5i + riociguat (Adempas) — profound hypotension

• sGC stimulator: riociguat (Adempas) 0.5→2.5 mg PO TID (PATENT-1: ↑6MWD 30 m ↓PVR; first-line for CTEPH Group 4 [CHEST-1: ↑6MWD 46 m])

• Prostacyclins (WHO FC III–IV or high-risk): IV epoprostenol (Flolan/Veletri) 2 ng/kg/min → titrate (most effective PAH therapy; NEVER stop → death; tunneled central catheter) · selexipag (Uptravi) 200→1600 mcg PO BID (GRIPHON: ↓morbidity/mortality 40%) · inhaled treprostinil (Tyvaso) 54 mcg QID · SC treprostinil (Remodulin)

• Vasoreactivity responders only (~10% of iPAH): amlodipine (Norvasc) 5–10 mg PO daily or diltiazem (Cardizem) ER 120–360 mg PO daily; reassess at 3–6 months — stop if no sustained response

• CTEPH Group 4: warfarin (Coumadin) INR 2–3 indefinitely · riociguat (Adempas) 0.5→2.5 mg PO TID · BPA (balloon pulm angioplasty) for inoperable · PEA surgery for proximal (potentially curative)

• O2: continuous if SpO2<92% at rest; nocturnal if <90% during sleep; with exertion if desaturation; hypoxia is the most important vasoconstrictor to avoid

• PT/OT — supervised low-intensity pulm rehab (EXERC trial: ↑6MWD+↑QoL); avoid supramaximal exertion (syncope); O2 during exercise; advance care planning for WHO FC IV

• Trend: WHO FC + 6MWD at every visit (↓>15%=worsening) · BNP/NT-proBNP (target↓) · echo annually or with clinical change (RV:LV ratio; pericardial effusion; TAPSE) · BMP (Cr/K+/Na+) · LFTs (ERA monitoring) · pregnancy test monthly if on ERA

• Escalate: acute RHF decompensation → IV milrinone (Primacor)+inhaled NO+Lasix IV+ICU · AF → cardiovert immediately · IV prostacyclin interruption → reconnect immediately (life-threatening emergency) · WHO FC IV failing dual therapy → IV epoprostenol (Flolan)+transplant listing · pericardial effusion on echo → ICU+pulm HTN specialist · worsening RV on RHC (CI<2.0; RAP>15) → transplant evaluation

• Discharge: ERA+PDE5i ± prostacyclin at max tolerated doses; O2 prescription; diuretics; warfarin (Coumadin) if CTEPH; progestin-only/IUD contraception (pregnancy=30–50% maternal mortality in FC III–IV); avoid altitude>1500 m; vaccines; PAH center f/u 4–6 weeks; advance care planning FC IV; return precautions: worsening exertional dyspnea+syncope+↑edema+pump alarm → ED immediately

PulmHTN-RHF

Pulmonary hypertension + right heart failure · WHO Groups 1–5 · all drug doses + trials · Full Card

Symptoms / Associated Sx

• Progressive exertional dyspnea (most common — insidious onset over months to years; often misattributed to deconditioning or obesity; median 2 years from symptoms to diagnosis); fatigue; reduced exercise tolerance; exertional chest pressure (RV ischemia from ↑wall stress)

• Exertional syncope — most ominous symptom; ↑RV afterload prevents CO augmentation with exertion → cerebral hypoperfusion; indicates severe disease and high near-term mortality risk

• RHF exam: JVD; HJR; pulsatile tender hepatomegaly; ascites; bilateral pitting edema; loud P2 (best at LUSB — slapping quality); parasternal RV heave; TR murmur (holosystolic LLSB, increases with inspiration — Carvallo sign); fixed split S2; prominent a or v waves in JVP

• Disease-specific clues: Raynaud + telangiectasias + skin thickening → SSc-PAH (screen annually); digital clubbing → Eisenmenger; prior DVT/PE → CTEPH; HIV risk factors; hepatosplenomegaly + ascites → portopulmonary

Neg

• Pt denies PCWP >15 mmHg on RHC — argues against Group 2 PH from left heart disease (most common PH overall; PAH-specific drugs in Group 2 increase pulmonary blood flow into a congested circuit → flash pulmonary edema and hemodynamic collapse; RHC is mandatory before initiating any PAH therapy; echo alone cannot reliably determine PCWP)

• Pt denies prior VTE + mismatched segmental perfusion defects on V/Q scan — argues against CTEPH Group 4 (V/Q is more sensitive than CT-PA for chronic clot; CTEPH is treated with riociguat [Adempas] + anticoag + BPA or PEA surgery, not standard ERA/PDE5i first-line)

• Pt denies significant airflow obstruction or restriction on PFTs + diffuse parenchymal changes on HRCT — argues against Group 3 PH from lung disease (COPD/ILD: supplemental O2 + treat underlying lung; PAH drugs have no proven benefit and may worsen V/Q mismatch in Group 3)

• Pt denies RV compression physiology with large pericardial effusion + RV diastolic collapse on echo — argues against cardiac tamponade mimicking RHF (tamponade: pericardiocentesis is the treatment, not PAH-targeted therapy)

Social History (SHx)

• Prior VTE/PE (CTEPH — anticoag history; IVC filter; V/Q scan); CTD (SSc — DETECT algorithm for PAH screening; anti-centromere antibody = limited SSc = highest PAH risk; anti-Scl-70 = diffuse SSc = highest ILD risk); HIV (1–2% lifetime PAH risk even on ART)

• Medications: appetite suppressants (fenfluramine — withdrawn), methamphetamines, dasatinib (Sprycel — TKI; reversible PAH); portal HTN/cirrhosis — portopulmonary (Group 1 subtype; liver transplant can cure if PAH mild); family hx BMPR2 mutation (autosomal dominant, 10–20% penetrance); pregnancy history (PAH in pregnancy = 30–50% maternal mortality)

Main Etiology — WHO Groups

• Group 1 PAH (pre-capillary, PCWP ≤15): idiopathic (BMPR2 somatic mutation; young women); heritable (BMPR2 germline, ~80% of heritable); CTD-associated (SSc most common); HIV; portopulmonary; Eisenmenger; drug/toxin-induced

• Group 2 (post-capillary, PCWP >15 — most common PH overall): HFpEF (most common subtype), HFrEF, valvular disease (MS → most severe pulmonary venous HTN), post-cardiac surgery

• Group 3 (lung disease/hypoxia): COPD (most common), IPF/ILD, OSA, hypoventilation syndromes, altitude

• Group 4 CTEPH: chronic thromboembolic occlusion after PE (3–5% of PE survivors); potentially surgically curable with PEA at expert center

• Group 5 (multifactorial): sarcoidosis, hemolytic anemia (sickle cell — NO scavenging), metabolic disorders, fibrosing mediastinitis

RF

• PAH: female sex (F:M 3:1 in iPAH), age 30–60, SSc (8–12% lifetime risk), BMPR2 mutation, fenfluramine/amphetamine use, HIV, portal HTN, uncorrected congenital heart disease

• CTEPH: prior PE (especially unprovoked/recurrent), non-O blood type, splenectomy, antiphospholipid antibody syndrome, ventriculoatrial shunt

• Group 3: COPD severity (FEV1 <30% = ↑PH risk), ILD fibrosis extent, severe OSA, obesity hypoventilation

Data

• Echo TTE (screening + monitoring) (TR jet velocity: <2.8 m/s = low probability; 2.8–3.4 m/s + signs = intermediate; >3.4 m/s = high probability; RV:LV ratio >1.0 = severe; D-sign = systolic septal flattening from RV pressure overload; pericardial effusion = poor prognosis marker; TAPSE <16 mm = ↓RV longitudinal function; IVC >21 mm with <50% collapse = elevated RAP)

• Right Heart Catheterization — mandatory before PAH therapy (mPAP >20 mmHg = PH [updated 2022 ESC from prior >25]; PVR ≥2 Wood units; PCWP ≤15 = pre-capillary [Groups 1/3/4/5]; PCWP >15 = post-capillary Group 2; vasoreactivity test: inhaled NO 10–20 ppm → positive = mPAP ↓≥10 to <40 WITH ↑CO → CCB trial candidate; only ~10% of iPAH respond; CTD-PAH rarely responds)

• V/Q scan (CTEPH screening: V/Q more sensitive than CT-PA for chronic clot; mismatched segmental/lobar perfusion defects = CTEPH pattern; normal V/Q essentially excludes CTEPH)

• PFTs with DLCO (FEV1/FVC <70% = COPD Group 3; restrictive pattern + reduced FVC = ILD; DLCO ↓ in PAH + ILD; severely ↓DLCO in SSc-ILD = poor prognosis)

• 6MWD at baseline and every visit (<165 m = high risk; 165–440 m = intermediate; >440 m = low risk per ESC/ERS 2022; ↓>15% from baseline = clinical worsening)

• BNP/NT-proBNP (BNP <50 pg/mL or NT-proBNP <300 = low risk; escalating values = disease progression; treatment target: ↓>30% from baseline)

• CTD serology (ANA, anti-Scl-70 [diffuse SSc=ILD], anti-centromere [limited SSc=PAH], anti-dsDNA [SLE], anti-U1-RNP [MCTD], RF + anti-CCP [RA])

• HIV serology, hepatitis B/C, LFTs + AFP (portopulmonary), antiphospholipid antibody panel (CTEPH risk), polysomnography (OSA Group 3), ABG (PaO2 <55 = O2 prescription)

DDx

Group 2 PH/LHD (PCWP >15 on RHC; treat LV; ERA/PDE5i contraindicated — worsen pulmonary congestion) · CTEPH Group 4 (prior PE + V/Q defects; riociguat [Adempas] + anticoag + BPA/PEA; potentially curative) · COPD/ILD Group 3 (PFTs + CT; supplemental O2 + treat lung; PAH drugs not beneficial) · Acute massive PE (acute onset + CT-PA + hemodynamic collapse; systemic tPA + anticoag) · Cardiac tamponade (pericardial effusion + RV diastolic collapse on echo; pericardiocentesis) · Portopulmonary HTN (portal HTN + PAH physiology; Group 1 subtype; liver transplant if PAH mild-moderate)

Home Meds

• NEVER abruptly stop IV or SC prostacyclin (epoprostenol [Flolan/Veletri]/treprostinil [Remodulin]) — rebound pulmonary vasoconstriction within hours → death; reconnect immediately if interrupted; patient and caregiver trained on pump management mandatory

• Continue: ERA + PDE5i + oral prostanoids (selexipag [Uptravi]); diuretics; warfarin (Coumadin) if CTEPH or iPAH anticoag indication

• Avoid: ACEi/ARB/BB (no benefit in Group 1 PAH; may worsen by ↓SVR or blunting HR response); NSAIDs; estrogen-containing OCP (↑VTE + ↑PAH risk); systemic vasodilators (nitrates/amlodipine [Norvasc]) in severe PAH without vasoreactivity testing; CCBs only if vasoreactivity-positive

Plan

• Classify before treating — RHC mandatory: PCWP ≤15 + PVR ≥2 WU = pre-capillary (proceed to PAH therapy); PCWP >15 = Group 2 (treat LV — HFrEF/HFpEF management; stop here); echo alone cannot classify; pulm HTN specialist consult Day 1

• Acute RHF stabilization:

  • O2 to SpO2 >92% immediately — hypoxia is a potent pulmonary vasoconstrictor; the most important acute intervention

  • Judicious diuresis: furosemide (Lasix) 40–80 mg IV; target CVP 8–12 mmHg; avoid over-diuresis (↓RV preload → ↓CO)

  • Vasopressor: vasopressin (Pitressin) 0.03–0.04 units/min preferred (↑SVR without ↑PVR; maintains RV coronary perfusion); norepinephrine (Levophed) 0.01–0.3 mcg/kg/min acceptable but may ↑PVR in severe Group 1

  • Inotrope: milrinone (Primacor) 0.1–0.375 mcg/kg/min (PDE3i — ↑RV inotropy + ↓PVR; preferred in acute RHF; use with vasopressor if hypotensive)

  • Selective pulmonary vasodilation: inhaled NO 10–40 ppm (↓PVR without ↓SVR) or inhaled iloprost (Ventavis) 5–20 mcg q2–4h or inhaled treprostinil (Tyvaso)

  • Avoid intubation if any alternative exists — PPV ↑PVR + ↓venous return → hemodynamic collapse; peri-intubation arrest >10% in severe PAH; if must intubate: vasopressin running + milrinone at bedside + minimal PEEP + defibrillator ready

  • AF → DC cardioversion immediately (atrial kick loss in hypertrophied stiff RV = hemodynamic emergency)

• Group 1 PAH targeted therapy:

  • Initial combination therapy (standard of care — AMBITION 2015, NEJM: ambrisentan [Letairis] + tadalafil [Adcirca] ↓clinical failure events 50% vs monotherapy; NNT ~5; first-line for WHO FC II–III)

  • ERA: macitentan (Opsumit) 10 mg PO daily (SERAPHIN 2013: ↓morbidity/mortality 45%; preferred long-term; teratogenic — monthly pregnancy test); ambrisentan (Letairis) 5→10 mg PO daily; bosentan (Tracleer) 62.5→125 mg PO BID (monthly LFTs — ↑transaminases in 10%)

  • PDE5 inhibitor: tadalafil (Adcirca) 40 mg PO daily (PHIRST: ↑6MWD 33 m; preferred — once daily); sildenafil (Revatio) 20 mg PO TID; NEVER combine PDE5i + riociguat (Adempas) — profound hypotension

  • sGC stimulator: riociguat (Adempas) 0.5→2.5 mg PO TID (PATENT-1: ↑6MWD 30 m, ↓PVR; alternative to PDE5i in Group 1; FIRST-LINE for Group 4 CTEPH [CHEST-1: ↑6MWD 46 m, ↓PVR 226 dyn·s·cm⁻⁵])

  • Prostacyclins/prostanoids (add for WHO FC III–IV or high-risk or inadequate response to dual oral): IV epoprostenol (Flolan/Veletri) 2 ng/kg/min → titrate over months (most effective PAH therapy; continuous tunneled central catheter; NEVER stop — death within hours); SC treprostinil (Remodulin) 1.25→80 ng/kg/min; inhaled treprostinil (Tyvaso DPI) 54 mcg QID; selexipag (Uptravi) 200→1600 mcg PO BID (GRIPHON 2015: ↓morbidity/mortality 40%)

  • Triple combination (ERA + PDE5i + prostacyclin) for high-risk disease or inadequate response to dual

• Vasoreactivity responders (~10% of iPAH; NOT CTD-PAH): amlodipine (Norvasc) 5–10 mg PO daily or nifedipine (Procardia XL) 60–120 mg PO daily; reassess at 3–6 months; if not sustained response → add PAH-specific therapy immediately

• Group 4 CTEPH: warfarin (Coumadin) INR 2–3 indefinitely; riociguat (Adempas) 0.5→2.5 mg PO TID; PEA (pulmonary endarterectomy) for proximal operable disease — potentially curative, <5% mortality at expert centers; BPA (balloon pulmonary angioplasty) for inoperable/distal CTEPH — serial sessions, meaningful ↓PVR

• Supplemental O2: continuous if PaO2 <55 mmHg or SpO2 <92% at rest; nocturnal if SpO2 <90% during sleep; with exertion if desaturation; air travel supplement for WHO FC III–IV (>1500 m altitude)

• PT/OT eval and treat — supervised low-intensity pulmonary rehab (EXERC trial: ↑6MWD + ↑QoL; avoid supramaximal exertion — syncope risk); fall precautions; ADL assessment; advance care planning for WHO FC IV

• Trend at every visit: WHO FC; 6MWD (↓>15% = worsening → escalate); BNP/NT-proBNP (target ↓>30%); BMP (Cr/K+/Na+ <130 = poor prognosis); echo (RV:LV ratio; pericardial effusion; TAPSE); LFTs (ERA monitoring — monthly for bosentan [Tracleer]; 3-monthly for others); pregnancy test monthly if on ERA (teratogenic)

• Escalation triggers: acute RHF decompensation (↓SBP + ↑JVD + ↓UO + ↑BNP) → IV milrinone + inhaled NO + furosemide (Lasix) IV + ICU · AF → cardiovert immediately · IV prostacyclin interruption → reconnect now (life-threatening) · WHO FC IV + failing dual oral → IV epoprostenol (Flolan) + transplant listing · pericardial effusion (new or enlarging) → ICU · RV:LV >2 on echo → ICU + PAH center

• Discharge: ERA + PDE5i ± prostacyclin at max tolerated doses; O2 at appropriate flow rate; diuretics (furosemide [Lasix] + spironolactone [Aldactone]); warfarin (Coumadin) if CTEPH or iPAH with anticoag indication; progestin-only or IUD contraception (pregnancy = 30–50% maternal mortality in FC III–IV); avoid altitude >1500 m; influenza + pneumococcal + COVID vaccines; PAH center f/u 4–6 weeks; advance care planning for FC IV; return precautions: worsening dyspnea + syncope + ↑edema + pump alarm → ED immediately

⚠ Red Flags

• IV prostacyclin (epoprostenol [Flolan/Veletri]) interruption → rebound severe pulmonary vasoconstriction within minutes to hours → hemodynamic collapse → death; the single most dangerous drug discontinuation in medicine; always have backup medication, backup pump; never stop without PAH specialist guidance

• PAH-specific drugs (ERA/PDE5i/prostacyclins) in Group 2 PH (PCWP >15) → ↑pulmonary blood flow into congested circuit → acute pulmonary edema; always confirm PCWP ≤15 on RHC before initiating PAH therapy; treating PH without knowing the group is dangerous

• Intubation in severe PAH → PPV ↑PVR + ↓venous return → hemodynamic collapse; peri-intubation arrest >10% in severe PAH; use NIV/HFNC as alternative; if must intubate: vasopressin + milrinone running, minimal PEEP, defibrillator at bedside

• AF in PAH → cardiovert immediately; atrial contribution critical to RV filling in pressure-overloaded RV; delayed cardioversion = hemodynamic collapse

• Pregnancy in PAH → 30–50% maternal mortality in WHO FC III–IV; contraindicated; progestin-only or IUD contraception mandatory; if pregnancy occurs → urgent PAH center + consider termination

• CCBs in non-vasoreactivity responders → ↓SVR → ↑R-to-L shunting → syncope; ONLY give CCBs after documented positive vasoreactivity test on RHC

Senior IM Resident Pearls

• WHO Group classification is the most important decision in PH: Group 2 (LHD) is the most common PH type overall; ERA/PDE5i are indicated only in Group 1 (and riociguat [Adempas] in Group 4 CTEPH); treating Group 2 with PAH drugs causes flash APE and death; RHC is mandatory — never start PAH therapy based on echo alone

• AMBITION trial (2015, NEJM): initial combination ambrisentan (Letairis) + tadalafil (Adcirca) vs monotherapy in WHO FC II–III → ↓clinical failure 50% (NNT ~5); combination therapy is now the standard first-line approach for most Group 1 PAH patients

• RHF physiology — 4 key differences from LHF: (1) vasopressin (Pitressin) preferred over norepinephrine (Levophed) alone (↑SVR without ↑PVR); (2) milrinone (Primacor) preferred inotrope (↓PVR + ↑inotropy); (3) avoid excessive IVF (worsens D-sign + ↓LV CO); (4) avoid intubation (PPV ↑PVR → arrest); these 4 distinctions from LHF management drive every acute RHF decision

• CTEPH — the curable PH: V/Q scan (not CT-PA) is the primary screening tool; riociguat (Adempas) is the only approved medical therapy; PEA surgery potentially curative at expert centers; always anticoag indefinitely; BPA for inoperable disease — often dramatic PVR improvement

• SSc screening — annual echo in ALL SSc patients: anti-centromere antibody = limited SSc = highest PAH risk (8–12% lifetime); DETECT algorithm for high-probability SSc-PAH; start screening at SSc diagnosis; early treatment dramatically improves outcomes

• Common mistake — diagnosing PAH by echo alone: TTE TR velocity is a screening tool only; a patient with TR velocity 3.5 m/s + PCWP 18 mmHg on RHC = Group 2, not Group 1; initiating ERA/PDE5i based on echo alone in Group 2 patients causes acute pulmonary edema; RHC before any PAH drug, always