01Approach to the Critical Patient/attcp47

Immediate stabilization

›Airway and oxygenation priorities

›Supplemental O2 to maintain SpO2 >90%

›High-flow nasal cannula for refractory hypoxemia

›Avoid intubation if at all possible

›Positive pressure ventilation dramatically worsens RV afterload

›If intubation unavoidable, use lowest PEEP possible and anticipate hemodynamic collapse

›Hemodynamic assessment

›Hypotension (SBP <90 mmHg) signals critical RV failure

›MAP target ≥65 mmHg

›Arterial line for continuous monitoring

›Avoid aggressive fluid resuscitation

›Most decompensated PH patients are volume overloaded

›Excess fluid worsens ventricular interdependence and LV compression

›Vasopressors preferred over fluids for hypotension

›Norepinephrine first-line: maintains systemic vascular resistance

›Vasopressin as adjunct to reduce norepinephrine requirements

›Inotropic support for low cardiac output

›Dobutamine 2–20 mcg/kg/min IV infusion

›Improves RV contractility and reduces pulmonary vascular resistance

›Risk of tachycardia and hypotension; titrate carefully

›Milrinone 0.375–0.75 mcg/kg/min IV infusion

›PDE3 inhibitor with pulmonary vasodilatory and inotropic effects

›Caution in renal impairment; may worsen systemic hypotension

Pulmonary vasodilator rescue

›Inhaled pulmonary vasodilators for acute RV failure

›Inhaled nitric oxide (iNO) 20–40 ppm

›Reduces pulmonary artery pressure without systemic hypotension

02History/hx64

Presenting symptoms

›Cardinal symptom: progressive exertional dyspnea

›Present in 60% of patients at disease onset

›Present in 98% of patients at time of diagnosis

›Initially exertional, progresses to rest symptoms in advanced disease

›Associated symptoms

›Fatigue and exercise intolerance

›Often preceding dyspnea recognition

›May be attributed to deconditioning causing diagnostic delay

›Chest pain (typically exertional)

›RV ischemia mechanism

›Pulmonary artery stretching

›Palpitations

›Sinus tachycardia most common

›Atrial arrhythmias in advanced disease

›Lightheadedness, presyncope, syncope

›Fixed low cardiac output state

›Exertional syncope indicates severely limited cardiac reserve

Alarm features

›High-risk presentations requiring immediate attention

›Exertional syncope or presyncope

›Inability to augment cardiac output with exertion

›High short-term mortality risk

›Rapid symptom progression over days to weeks

›Acute decompensation vs. chronic progression

›Signs of right heart failure

›Lower extremity edema

›Abdominal distension (ascites)

03Physical Exam/exam40

Vital signs and hemodynamics

›Vital sign pattern in PH

›Tachycardia at rest or with minimal exertion

›Compensatory sinus tachycardia for low stroke volume

›Resting HR >100 bpm suggests significantly impaired cardiac output

›Hypotension in advanced disease

›SBP <90 mmHg indicates decompensated RV failure

›Oxygen saturation

›Resting hypoxemia suggests parenchymal lung disease contribution

›Desaturation on 6-minute walk test: functional marker

Cardiovascular exam

›Auscultation findings

›Loud P2 (pulmonic component of S2)

›Pathognomonic of elevated pulmonary artery pressure

›Heard best at left upper sternal border

›May be palpable as parasternal impulse

›Right-sided S3 (tricuspid area) indicates RV failure

›Pulmonic regurgitation murmur (high-pitched decrescendo diastolic)

›Tricuspid regurgitation murmur (holosystolic, increases with inspiration)

›Indicates RV dilation and annular dilatation

›RV heave assessment

›Left parasternal lift from RV hypertrophy

›Prominent a-wave in jugular venous pulsations (RV non-compliance)

›Large v-wave in JVP indicates tricuspid regurgitation

Signs of right heart failure

›Volume overload findings

›Elevated JVP (>4 cm above sternal angle)

›Most sensitive marker of elevated right atrial pressure

04Differential Diagnosis/ddx37

Life-threatening mimics

›Acute pulmonary embolism

›ICD-10: I26.09 (without cor pulmonale), I26.99 (unspecified)

›Acute onset vs. PH insidious onset

›CT-PA diagnostic; elevated troponin and BNP from acute RV strain

›Acute decompensated heart failure

›ICD-10: I50.9

›Bilateral crackles, pulmonary edema on CXR, elevated PAWP

›Orthopnea and paroxysmal nocturnal dyspnea more prominent

›Cardiac tamponade

›ICD-10: I31.4

›Pulsus paradoxus, elevated JVP, muffled heart sounds

›Echo confirms pericardial effusion with chamber compression

WHO classification differential

›Group 2: Left heart disease (most common cause of PH)

›HFpEF, HFrEF, valvular disease

›PAWP >15 mmHg on RHC distinguishes from PAH

›ICD-10: I27.2 (other secondary PH)

›Group 3: Chronic lung disease and hypoxia

›COPD, ILD, OSA, obesity hypoventilation syndrome

›PFTs and HRCT characterize parenchymal disease

›ICD-10: I27.2

›Group 4: CTEPH

›ICD-10: I27.24

›Mismatched perfusion defects on V/Q scan pathognomonic

›Must be excluded before diagnosing Group 1 PAH

›Group 1: Pulmonary arterial hypertension

›Idiopathic PAH: ICD-10 I27.0

05Laboratory Tests/lt44

Initial workup

›Complete blood count

›Polycythemia suggests chronic hypoxemia (Group 3) or cyanotic CHD

›Anemia worsens PH symptoms and RV oxygen delivery

›Thrombocytopenia in portal hypertension-associated PAH

›Metabolic panel

›Renal function: creatinine elevated with low cardiac output or diuretics

›Liver enzymes: elevation reflects hepatic congestion from RV failure

›Sodium: hyponatremia marker of advanced hemodynamic compromise

›Uric acid: elevated in PH correlates with reduced cardiac output

›Coagulation studies

›INR/PT: liver dysfunction from hepatic congestion

›Lupus anticoagulant and antiphospholipid antibodies for CTEPH workup

Cardiac biomarkers

›BNP or NT-proBNP

›Elevated in proportion to RV pressure and volume overload

›NT-proBNP >1800 ng/l associated with high-risk PAH (ESC/ERS)

›NT-proBNP >300 ng/l warrants further evaluation for PH

›Serial measurement monitors treatment response

›Troponin (high-sensitivity)

›Elevated in RV ischemia from elevated wall tension

›Predictor of worse outcomes in acute decompensation

›Elevated troponin T >0.02 mcg/l associated with mortality risk

Connective tissue and autoimmune serology

›ANA screen with reflex testing

›Anti-Scl-70 (anti-topoisomerase I): diffuse systemic sclerosis

›Anti-centromere antibody: limited systemic sclerosis (CREST)

›Anti-dsDNA, anti-Smith: SLE

06Diagnostic Tests/dt70

Scoring Systems

›ESC/ERS risk stratification (2022 guidelines)

›Low risk (1-year mortality <5%): all of WHO FC I-II, 6MWD >440 m, NT-proBNP <300 ng/l, no RV dysfunction on echo/CMR, RAP <8 mmHg, CI >2.5 l/min/m2

›Intermediate risk (5–20%): values between low and high risk

›High risk (>20%): WHO FC IV, 6MWD <165 m, NT-proBNP >1800 ng/l, pericardial effusion, RAP >14 mmHg, CI <2.0 l/min/m2

›Treatment escalation targets achieving low-risk profile

›REVEAL 2.0 Risk Score

›Variables: WHO group, FC, 6MWD, NT-proBNP, hemodynamics, demographics

›Score ≤6: low risk; 7–8: intermediate; ≥9: high risk

›Validated in US registry for predicting 1-year mortality

›WHO Functional Class

›I: No symptoms with ordinary activity; no limitation

›II: Slight limitation; comfortable at rest; symptoms with ordinary activity

›III: Marked limitation; comfortable at rest; symptoms with less than ordinary activity

›IV: Unable to perform any activity; symptoms at rest; right heart failure signs

MRI

›Cardiac MRI (CMR) for RV assessment

›Gold standard for RV size and function quantification

›RV ejection fraction <35% associated with high mortality risk

›RV end-diastolic volume index >84 ml/m2: high-risk feature

›RV mass index elevation correlates with disease severity

›Late gadolinium enhancement: RV insertion point fibrosis common in PAH

›Septal flattening (D-sign) quantifiable; reflects ventricular interdependence

›CMR in CTEPH evaluation

›Thromboembolic material in proximal pulmonary arteries visible

›RV-PA coupling assessment

›Perfusion CMR emerging as radiation-free V/Q alternative

›Limitations of CMR

›Not available acutely in most centers

›Incompatible with many implanted cardiac devices

›Requires patient cooperation for breath-holding sequences

›Claustrophobia in ~5% of patients

CT

›CT pulmonary angiography (CT-PA)

›Indications: suspected acute PE, CTEPH workup, anatomy of pulmonary vasculature

›Signs of chronic CTEPH on CT-PA: mosaic perfusion, web/band filling defects, pruning of peripheral vessels

›Main pulmonary artery diameter >29 mm: sensitive marker for PH (sensitivity 69%, specificity 93%)

›PA:aorta ratio >1.0 suggests elevated PA pressure

›High-resolution CT (HRCT) of chest

›Parenchymal disease characterization (ILD, emphysema, PVOD)

›Mosaic attenuation: CTEPH pattern (geographic distribution)

›Ground-glass opacities + septal thickening: PVOD or pulmonary capillary hemangiomatosis

›Lymphadenopathy: sarcoidosis-associated PH

›Ventilation-Perfusion (V/Q) scan

›First-line to exclude CTEPH before PAH diagnosis (ESC/ERS Class I)

›Mismatched perfusion defects pathognomonic for CTEPH

›Sensitivity for CTEPH ~96–97%; superior to CT-PA for CTEPH detection

›Normal V/Q effectively excludes CTEPH

Ultrasound

›Transthoracic echocardiography (TTE)

›First-line imaging test; ESC/ERS Class I recommendation for suspected PH

›Estimated RVSP from TR jet velocity using modified Bernoulli equation

›TR peak velocity >3.4 m/s: high probability of PH

›TR peak velocity 2.9–3.4 m/s with supporting signs: intermediate probability

›TR peak velocity <2.8 m/s: low PH probability

›Doppler TTE sensitivity 79–85%, specificity 68–72% for PH detection (Cochrane 2022)

›Does not replace RHC for definitive diagnosis

›Additional echo markers of PH severity

›RV/LV basal diameter ratio >1.0: RV enlargement

›Septal flattening (D-sign) in systole: pressure overload; diastole: volume overload

›TAPSE <18 mm: RV systolic dysfunction (prognostic marker)

›Pericardial effusion: high-risk feature; even small effusion worsens prognosis

›RA area >18 cm2: elevated RA pressure marker

›Point-of-care ultrasound in acute PH

›RV dilation (RV:LV ratio) at bedside for rapid RV failure diagnosis

›IVC plethora (IVC >21 mm with <50% collapse): elevated RA pressure

›Absence of LV dilation helps distinguish from Group 2 PH

›Right heart catheterization (RHC)

›Gold standard for definitive diagnosis; required before initiating PAH therapy

›PAH diagnostic criteria: mPAP >20 mmHg + PAWP ≤15 mmHg + PVR ≥3 Wood units

›Complication rate: serious complications 1.1%, procedure-related death 0.055%

›Acute vasoreactivity testing with inhaled NO during RHC

›Positive: mPAP decrease ≥10 mmHg to <40 mmHg with stable/increased CO

›Identifies candidates for calcium channel blocker therapy (~10% of IPAH)

07Disposition/dispo31

ICU admission criteria

›Critical indicators for ICU-level care

›Hemodynamic instability: SBP <90 mmHg despite initial resuscitation

›Exertional syncope or frank syncope episode

›Rising lactate (>2 mmol/l) indicating low cardiac output

›Refractory hypoxemia despite high-flow oxygen

›New-onset arrhythmia with hemodynamic compromise

›Interruption or malfunction of prostacyclin infusion device

›Acute right heart failure with end-organ dysfunction

›Rising creatinine indicating renal hypoperfusion

›Transaminase elevation indicating hepatic congestion

›Newly diagnosed PH with high-risk features on presentation

Telemetry/ward admission criteria

›Indications for monitored non-ICU admission

›Decompensated right heart failure requiring IV diuresis

›Furosemide 40–80 mg IV to restore euvolemia

›Daily weights and strict fluid balance monitoring

›New diagnosis of PH requiring diagnostic workup

›TTE, ECG, labs, and subspecialty consultation

›Significant hypoxemia requiring supplemental O2 titration

›Worsening edema or ascites not responding to oral diuretics

Transfer criteria

›Transfer to PH referral center

›All patients with suspected or confirmed PAH or CTEPH

›ESC/ERS Class I recommendation

›RHC, vasoreactivity testing, and treatment initiation at expert center

›Refractory hemodynamic instability requiring ECMO consideration

›CTEPH patients who may be candidates for pulmonary endarterectomy

08Treatment/t137

Acute resuscitation

›Oxygen therapy

›Supplemental O2 to target SpO2 >90%

›Hypoxemia is a potent pulmonary vasoconstrictor

›High-flow nasal cannula at 30–60 L/min for refractory hypoxemia

›Avoid intubation unless absolutely necessary

›Positive pressure ventilation increases RV afterload

›If intubating: ketamine induction preferred (maintains SVR); avoid propofol bolus

›Use lowest FiO2 and PEEP to maintain oxygenation

›Vasopressor therapy

›Norepinephrine 0.01–3.0 mcg/kg/min IV infusion (preferred vasopressor)

›Maintains systemic vascular resistance, countering vasodilatory shock

›Prevents coronary ischemia of hypertrophied RV

›Titrate to MAP ≥65 mmHg

›Vasopressin 0.01–0.04 units/min IV (adjunct)

›Reduces norepinephrine requirements

›Pulmonary vasodilatory effect via V1 receptors at low doses

›Phenylephrine: avoid (reflex bradycardia may worsen CO)

›Inotropes for RV failure

›Dobutamine 2–20 mcg/kg/min IV infusion

›Start at 2–5 mcg/kg/min; titrate every 10–15 min

›Reduces PVR and improves RV contractility

›Monitor for tachycardia (dose-limiting in many patients)

›Milrinone 0.125–0.75 mcg/kg/min IV infusion

›Loading dose 50 mcg/kg over 10 min (may omit to avoid hypotension)

›PDE3 inhibition: inotropic + pulmonary vasodilatory

›Reduce dose by 50% in eGFR <30 ml/min

Inhaled pulmonary vasodilators

›Inhaled nitric oxide (iNO)

›Dose: 20–40 ppm continuous delivery

›Reduces mPAP and PVR without systemic vasodilation

›Selective pulmonary vasodilation via local V/Q matching

›Monitoring: methemoglobin level every 4–8 hours

›Wean gradually to prevent rebound PH on discontinuation

›Inhaled epoprostenol (prostacyclin)

›Dose: 10,000–50,000 ng/ml solution nebulized at 0.5 mL/hr via ventilator

›Duration of effect: 30–60 minutes

›Alternative when iNO unavailable

›Inhaled iloprost: 2.5–5 mcg per inhalation, 6–9 times daily

›Available for spontaneously breathing patients

›IV epoprostenol for refractory acute PH crisis

›Initiate at 2 ng/kg/min; titrate by 2 ng/kg/min every 15 minutes

›Requires central venous access (dedicated line)

›Profound systemic hypotension risk; requires vasopressor support

›Long-term if patient transitions to chronic PAH management

Chronic PAH pharmacotherapy

›Endothelin receptor antagonists (ERAs)

›Ambrisentan 5–10 mg PO once daily

›ERA selective for ETA receptor subtype

›Avoid in pregnancy (teratogenic; Category X)

›Monthly liver function monitoring no longer required but monitor clinically

›Macitentan 10 mg PO once daily

›Dual ETA/ETB receptor antagonist

›SERAPHIN trial: 45% reduction in morbidity/mortality events

›Monthly pregnancy testing required; strict contraception

›Bosentan 62.5 mg PO twice daily for 4 weeks then 125 mg PO twice daily

›Dual ETA/ETB receptor antagonist

›Monthly LFTs required due to hepatotoxicity risk

›PDE5 inhibitors

›Sildenafil 20 mg PO three times daily

›SUPER-1 trial: improvement in 6MWD and hemodynamics

›Contraindicated with nitrates (severe hypotension)

›Contraindicated with riociguat (same downstream pathway)

›Tadalafil 40 mg PO once daily

›PHIRST trial: improved 6MWD and reduced clinical worsening

›Once-daily dosing advantage over sildenafil

›Soluble guanylate cyclase stimulator

›Riociguat 1 mg PO three times daily; titrate by 0.5 mg every 2 weeks

›Maximum 2.5 mg three times daily

›PATENT-1 trial: improved 6MWD and hemodynamics in PAH

›CHEST-1 trial: approved for inoperable CTEPH

›Contraindicated with PDE5 inhibitors and nitrates

›Prostacyclin pathway agents

›IV epoprostenol (Flolan, Veletri)

›Start 2 ng/kg/min; titrate by 1–2 ng/kg/min every 15 min to tolerance

›Long-term dose typically 20–40 ng/kg/min

›Requires permanent central venous catheter; medication never stopped

›Most effective therapy for severe/high-risk PAH

›SC treprostinil (Remodulin)

›Start 1.25 ng/kg/min; titrate by 1.25 ng/kg/min per week

›Subcutaneous site pain is dose-limiting in ~20% of patients

›Also available as IV formulation

›Inhaled treprostinil (Tyvaso)

›54 mcg (3 breaths) 4 times daily; titrate to 72 mcg (4 breaths) 4 times daily

›Approved for PAH and ILD-associated PH (INCREASE trial)

›Oral selexipag (Uptravi)

›Start 200 mcg twice daily; titrate weekly by 200 mcg to maximum tolerated dose (up to 1600 mcg twice daily)

›GRIPHON trial: 40% reduction in composite morbidity/mortality

›Not a prostacyclin; selective IP receptor agonist

›Oral treprostinil (Orenitram)

›Requires frequent dosing; GI side effects limit tolerability

Combination therapy strategies

›Initial combination therapy for newly diagnosed PAH

›Low/intermediate risk: dual oral combination preferred

›ERA + PDE5 inhibitor (e.g., ambrisentan + tadalafil; AMBITION trial)

›AMBITION trial: 50% reduction in clinical failure vs. monotherapy

›Macitentan + tadalafil: MASTER trial evidence

›High risk: triple therapy including IV/SC prostacyclin

›ERA + PDE5i + IV epoprostenol or SC treprostinil

›Escalation strategy

›Reassess risk every 3–6 months using ESC/ERS or REVEAL 2.0

›Escalate therapy if low-risk status not achieved

›Sequential addition of prostacyclin pathway agent

Calcium channel blockers (selected patients only)

›Reserved for vasoreactivity-positive IPAH/HPAH

›Nifedipine extended-release 30–240 mg/day PO

›Diltiazem 240–720 mg/day PO (if resting tachycardia)

›Amlodipine 2.5–20 mg/day PO (alternative)

›Contraindicated without positive vasoreactivity test on RHC

›Follow-up RHC at 3–4 months to confirm sustained response

Supportive therapies

›Diuretics for volume management

›Furosemide 20–80 mg PO daily (titrate to euvolemia)

›IV formulation 40–80 mg for acute decompensation

›Spironolactone 25–50 mg PO daily as adjunct

›Potassium-sparing; useful with loop diuretics

›Target weight loss 0.5–1.0 kg/day during decongestion phase

›Anticoagulation (selected patients)

›Warfarin (target INR 1.5–2.5): IPAH patients with evidence from small studies

›No longer universally recommended; individualize based on risk-benefit

›Chronic anticoagulation: mandatory for all CTEPH patients

›Warfarin or DOAC (evidence for DOACs emerging)

›Supplemental oxygen

›Continuous home O2 if resting SpO2 <90% or nocturnal desaturation confirmed

›Target SpO2 >90% at rest

›Iron supplementation

›IV ferric carboxymaltose if IV iron deficiency detected

›Oral iron poorly absorbed in PAH due to hepcidin dysregulation

Surgical and interventional options

›Pulmonary endarterectomy (PEA)

›Treatment of choice for operable CTEPH

›Curative potential; normalizes hemodynamics in most patients

›Performed at experienced centers under deep hypothermic circulatory arrest

›30-day mortality at expert centers: 2–4%

›Balloon pulmonary angioplasty (BPA)

›For inoperable CTEPH or residual/recurrent CTEPH after PEA

›Multiple staged sessions targeting obstructed vessels

›Atrial septostomy

›Palliative; creates right-to-left shunt to decompress RV

›Considered as bridge to transplant or when other options exhausted

›Lung transplantation

›Bilateral sequential lung transplant preferred for PAH

›Consider referral when WHO FC III–IV despite maximal therapy

›Median survival post-transplant 5–6 years

09Special Populations/sp67

Pregnancy

›Risk stratification in PH

›Pregnancy carries extremely high maternal mortality in PAH

›Historical mortality 30–56%; recent data with expert center care 11–25%

›Maternal death risk primarily from decompensated RV failure at delivery and postpartum

›ESC/ERS: pregnancy contraindicated in severe PAH (Class I recommendation)

›Physiologic changes that worsen PH

›Increased plasma volume (50% increase by 32 weeks)

›Decreased systemic vascular resistance

›Increased cardiac output demand by 30–50%

›Autotransfusion at delivery can precipitate acute decompensation

›Medication safety in pregnancy

›ERAs: teratogenic; absolutely contraindicated

›Require monthly pregnancy testing in women of childbearing potential

›Two forms of contraception required

›Riociguat: Category X; contraindicated

›PDE5 inhibitors: generally considered safer; limited human data

›Prostacyclins: considered for use if PH diagnosed during pregnancy

›IV epoprostenol used in highest-risk pregnant patients

›Warfarin: crosses placenta; embryopathy risk in first trimester

›Transition to LMWH in first trimester and near delivery

›Management if pregnant with PH

›Expert center management mandatory

›Planned delivery at 34–36 weeks gestation

›Epidural analgesia preferred; avoid general anesthesia if possible

›Postpartum period highest risk: continued monitoring for 1–2 weeks

›Contraception counseling mandatory after delivery

Geriatric

›Epidemiology in elderly

›Group 2 PH (left heart disease) predominates in patients >65 years

›HFpEF-associated PH increasingly recognized; PAWP >15 mmHg critical to distinguish

›Idiopathic PAH occurs at any age but less common in elderly

›Diagnostic considerations

›Higher prevalence of comorbidities confounds symptoms

›Dyspnea from COPD, deconditioning, heart failure, or PH may overlap

›Exercise intolerance often attributed to aging rather than investigated

›Echocardiography remains first-line; RHC still required for definitive diagnosis

›Treatment modifications in elderly

›PAH-targeted therapies generally used with standard dosing

›Reduced renal clearance affects treprostinil and sildenafil

›Monitor for hypotension with PDE5 inhibitors (concurrent antihypertensives)

›Higher bleeding risk with anticoagulation; careful INR management

›Falls risk with vasodilator-induced hypotension

›Group 2 PH: optimize heart failure therapy; avoid PAH-specific agents

›PDE5 inhibitors shown harmful post-valvular surgery

Pediatrics

›Pediatric PH spectrum

›Persistent pulmonary hypertension of newborn (PPHN)

›ICD-10: P29.30

›Failed adaptation at birth with persistence of high PVR

›Treatment: iNO 20 ppm; ECMO for refractory cases

›Bronchopulmonary dysplasia-associated PH

›Most common PH etiology in preterm infants

›Optimize respiratory support and nutrition

›Pediatric PAH (>3 months age)

›BMPR2 mutations more commonly identified than in adult IPAH

›More aggressive disease course compared to adults

›Diagnostic approach in children

›PH defined as mPAP >20 mmHg after age 3 months

›PVR ≥3 Wood units x m2 (indexed)

›Echocardiography essential; requires pediatric expertise

›Congenital heart disease workup mandatory

›Pediatric treatment considerations

›Sildenafil: FDA approved for pediatric PAH

›Weight-based dosing; FDA warning against high doses in children (increased mortality signal)

›Low dose: 0.5 mg/kg/dose three times daily

›Bosentan: approved for children >2 years (2 mg/kg twice daily, max 62.5 mg)

›IV epoprostenol: used in high-risk pediatric PAH

›Vasoreactivity testing performed at expert centers only

›Lung transplant center referral for high-risk disease

10Background/b60

Epidemiology

›Prevalence and incidence of PAH (Group 1)

›Prevalence approximately 10–50 per million adults in the US and Europe

›Annual incidence approximately 1.1–7.6 per million adults

›Female predominance: female:male ratio approximately 3:1 for IPAH

›Age distribution: bimodal; younger onset for IPAH, older for associated forms

›Pulmonary hypertension overall (all groups)

›Group 2 (left heart disease) accounts for majority (~65–80%) of all PH cases

›Group 3 (lung disease): second most common, primarily COPD and ILD populations

›Group 4 CTEPH: estimated 0.5–5% of patients surviving acute PE develop CTEPH

›Mortality and prognosis

›IPAH median survival prior to modern therapy: 2.8 years from diagnosis

›5-year survival improved from 34% (1991) to >60% (2015) with modern combination therapies

›High-risk PAH (WHO FC IV): 1-year mortality >15–20% despite therapy

›CTEPH post-PEA: 5-year survival >80% at experienced centers

Pathophysiology

›Pulmonary vascular remodeling in PAH

›Endothelial dysfunction: reduced prostacyclin and nitric oxide, excess endothelin-1

›Prostacyclin deficiency: increased platelet aggregation and vasoconstriction

›NO pathway impairment: reduced cGMP-mediated vasodilation

›Endothelin-1 excess: potent vasoconstrictor and smooth muscle mitogen

›Smooth muscle cell proliferation and hypertrophy of media

›Adventitial fibrosis and inflammation

›Plexiform lesions: pathognomonic of severe PAH; near-neoplastic proliferative channels

›In situ thrombosis contributes to increased PVR

›RV adaptation and failure

›Adaptive RV hypertrophy: Starling and Frank-Starling mechanisms

›Initially maintains cardiac output against elevated afterload

›RV-PA uncoupling: RV fails to maintain stroke volume as PVR rises

›Ventricular interdependence: dilated RV compresses LV via shared interventricular septum

›Septal flattening and D-sign reflect this compression

›Impaired LV filling reduces systemic cardiac output

›RV ischemia: increased O2 demand + reduced coronary perfusion from low aortic pressure

›WHO group-specific mechanisms

›Group 2: Elevated left-sided filling pressures transmitted to pulmonary vasculature

›Reactive component: vasoconstriction responsive to pulmonary vasodilators

›Fixed component: structural remodeling after prolonged exposure

›Group 3: Hypoxic pulmonary vasoconstriction (HPV) chronically elevates PVR

›Group 4 CTEPH: Mechanical obstruction by organized thrombus + distal vasculopathy

›BMPR2 mutation (heritable PAH): impaired TGF-beta signaling → endothelial and smooth muscle dysregulation

Therapeutic Considerations

›Treatment target: achieving low-risk profile

›WHO FC I or II at follow-up

›6MWD >440 m (or individually meaningful improvement)

›NT-proBNP <300 ng/l

›No pericardial effusion or RV dysfunction on echo

›Hemodynamics: RAP <8 mmHg, CI >2.5 l/min/m2, PVR <4 Wood units

›Mechanism-based drug class effects

›ERAs block endothelin-1 binding: reduce vasoconstriction and remodeling

›PDE5 inhibitors increase cGMP: vasodilation and antiproliferative effects

›Prostacyclin analogues: vasodilation, antiproliferative, antiplatelet effects

›Riociguat directly stimulates sGC independent of endogenous NO

›Evidence base for combination therapy

›AMBITION trial: upfront ambrisentan + tadalafil reduced clinical failure 50% vs. monotherapy

›GRIPHON trial: selexipag reduced morbidity/mortality by 40% added to background ERA/PDE5i

›Cochrane 2025 review: PDE5i + ERA combination superior to either alone for Group 1 PAH

›Group-specific therapy principles

›Group 2: Optimize HF and valvular disease management; PAH therapies generally not beneficial

›PDE5 inhibitors shown to increase hospitalizations in some post-valvular surgery patients

›Group 3: Treat underlying lung disease; inhaled treprostinil FDA-approved for ILD-PH

›INCREASE trial: inhaled treprostinil improved 6MWD in ILD-associated PH

›Group 4 CTEPH: surgical PEA first-line; riociguat for inoperable; BPA for selected cases

›Group 5: Treat underlying systemic condition

11Patient Discharge Instructions/pdi37

copy discharge instructions

›Diagnosis and disease understanding

›Pulmonary hypertension (high pressure in the lung blood vessels) has been diagnosed or evaluated today

›This is a chronic condition requiring ongoing specialist management

›Your condition requires close follow-up with a pulmonary hypertension specialist

›Medication instructions

›Take all prescribed pulmonary hypertension medications exactly as directed

›Never stop or skip your PAH medications without talking to your doctor first

›Stopping prostacyclin infusions (Flolan, Remodulin) can be life-threatening

›Even brief interruptions of IV/SC prostacyclin can cause severe rebound symptoms

›If you have an infusion pump, check it regularly; call your nurse coordinator immediately if any pump alarms

›Take diuretics (water pills) at the same time each day

›Weigh yourself every morning; call your doctor if weight increases >2 kg in 24 hours or >3 kg in 3 days

›Activity and lifestyle

›Supervised exercise rehabilitation is recommended; avoid unsupervised strenuous exertion

›Stop any activity that causes dizziness, chest pain, or shortness of breath

›Avoid high altitude (>1500 m) without discussing with your specialist

›Sodium restriction: limit sodium to <2000 mg per day

›Daily fluid restriction may be recommended by your specialist

›Avoid excessive alcohol consumption

›Avoid pregnancy: speak with your doctor about effective contraception

›Pregnancy carries very high risk of serious complications with pulmonary hypertension

›Vaccinations

›Ensure up-to-date influenza vaccination (annually)

›Pneumococcal vaccine as recommended

›COVID-19 vaccine series completed

›Follow-up plan

›Pulmonary hypertension specialist appointment within 1–2 weeks

12References/r30

Guidelines and key sources

›Ruopp NF, Cockrill BA. Diagnosis and Treatment of Pulmonary Arterial Hypertension: A Review. JAMA. 2022. doi:10.1001/jama.2022.4402

›Comprehensive PAH review grounding clinical presentation, diagnostics, and treatment

›Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. Eur Respir J. 2023. PMID:36028254

›Current international guideline; basis for risk stratification and treatment algorithm

›Hassoun PM. Pulmonary Arterial Hypertension. N Engl J Med. 2021. doi:10.1056/NEJMra2000348

›Landmark NEJM review; treatment algorithm and pathophysiology

›McLaughlin VV, Shah SJ, Souza R, Humbert M. Management of Pulmonary Arterial Hypertension. J Am Coll Cardiol. 2015. PMID:25953750

›JACC management framework; combination therapy evidence

›Mandras SA, Mehta HS, Vaidya A. Pulmonary Hypertension: A Brief Guide for Clinicians. Mayo Clin Proc. 2020. PMID:32861339

›Practical clinician-focused overview; diet, follow-up, and referral patterns

›Latimer K, Layne M, Payne M. Pulmonary Hypertension. Am Fam Physician. 2024. PMID:39172676

›Primary care and emergency perspective; discharge and follow-up guidance

Landmark trials and specialty guidelines

›Expert Panel on Thoracic Imaging, Sirajuddin A, et al. ACR Appropriateness Criteria Suspected Pulmonary Hypertension: 2022 Update. J Am Coll Radiol. 2022. doi:10.1016/j.jacr.2022.09.018

›Imaging protocol recommendations for suspected PH

›Rajagopal S, Ruetzler K, Ghadimi K, et al. Evaluation and Management of PH in Noncardiac Surgery: AHA Scientific Statement. Circulation. 2023

›Perioperative PH management; vasopressor and inotrope evidence

›Savale L, Kularatne M, Roche A, et al. Management of Acutely Decompensated Pulmonary Hypertension. Semin Respir Crit Care Med. 2023. PMID:37369216

›ICU management of PH crisis; vasopressor and vasodilator strategies

›Houston BA, Brittain EL, Tedford RJ. Right Ventricular Failure. N Engl J Med. 2023. doi:10.1056/NEJMra2207410

›RV failure pathophysiology, inotropes, and mechanical support

›Tsujimoto Y, Kumasawa J, Shimizu S, et al. Doppler TTE for Detection of PH: Cochrane Review. 2022. doi:10.1002/14651858.CD012809.pub2

›Echocardiography diagnostic performance evidence

›Oba Y, Maduke T, Fakhouri EW, Goite Y. PDE5 Inhibitor Plus ERA for Group 1 PAH: Cochrane Review. 2025. doi:10.1002/14651858.CD015824.pub2

›Combination therapy evidence for PAH

›Mukherjee M, Rudski LG, Addetia K, et al. ASE Guidelines for Echocardiographic Assessment of Right Heart in Adults. J Am Soc Echocardiogr. 2025

›Echo parameters for RV assessment and PH severity

Evidence & Review

Evidence & Review