from st.paul hospital millenium medical college ethiopia addis abeba

1. Update on management of pulmonary HTN
• Introduction
• Pathophysiology
• Clinical features
• Management principle
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2. • 6th WSPC Changes
• Definition
• Classifications
• Therapeutic
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3. Introduction
• Estimated overall population 1%
• Above 65 year of age accounts about 10%
• 7 fold higher incidence of G1 PAH in women
• 80% underdeveloped countries….limited access medical services
N ENGL.J MED 385;25 NEJM.ORG DECEMBER 16,2021
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4. Introduction…
• Pulmonary vascular system
• Normally a high-flow
• Low-resistance circuit
• Mean PAP that constitutes>15% to 20% of the systemic circulation
• PA systolic pressures range from 15 to 30 mm Hg, and diastolic 4 to 12 mm Hg
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5. Introduction…
• PH exists when a mPAP is >25 mm Hg at rest or >30 mm Hg during exertion
• Pulmonary arterial pressure
• Pulmonary vascular resistance, and
• Pulmonary capillary wedge pressure
• Echocardiography
• Right heart catheterization
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6. Introduction…
• Patients with pulmonary arterial hypertension have
• mean pulmonary arterial pressure >25 mm Hg
• pulmonary vascular resistance >240 dynes/s/cm5 , and
• pulmonary capillary wedge pressure<15
• A 5-year death rate for patients with idiopathic pulmonary arterial hypertension
exceeding 30%
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7. New definition
• pulmonary vascular resistance ⩾3 Wood Units and
• pre-capillary PH associated with mPAP >20 mmHg
• clinical classification of PH
• pre-capillary PH patients from groups 1, 3 and 4
• some patients from group 5, and
• rarely patients from group 2 with combined pre- and post-capillary PH
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9. WHO Classification of Pulmonary
Hypertension
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10. Pathophysiology
• Pulmonary arterial hypertension consists of
• Vascular remodeling in all layers of pulmonary arterioles, plus
• Inflammation and
• In situ thrombosis formation
• Additional pathology includes
• Alterations in microvascular permeability,
• Hypoxic vasoconstriction, and
• Plexiform lesion formation in arteriolar walls
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11. Cont…
History
• Nonspecific
• Should be considered for patients with
• Exertional dyspnea
• Syncope
• Angina and progressive limitation of exercise
• Symptom of right ventricular failure
• Fatigue
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12. Cont…
Physical examination
• Normal in the early stages
• Signs of RV failure
-Holosystolic murmur(TR)
-Jugular venous distention (prominent A wave )
-Hepatomegaly
-Ascites, lower extremity edema
• Pulmonary [P2] acentuation , Parasternal heave
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13. Diagnostic evaluation
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• Approach…?
• Investigations….?

14. Cont…
• R/S ratio in V1 >1
• right axis deviation, and
• ST depressions in V3 to V5
• indicating possible right
ventricular strain
• Afib
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15. Cont…
ECG
• Right axis deviation
• Signs of RV hypertrophy or RV failure
-R/S ratio >1 or a qR complex in lead V1
-R/S ratio <1 in lead V5 and V6
-S1Q3T3
-Right atrial enlargement in the inferior leads,
-Incomplete or complete RBBB
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16. Cont…
Most common dysrhythmias in patients with pulmonary hypertension??
• Atrial fibrillation, atrial flutter, and AVnRT
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17. Cont…
ANALYSIS ECG Findindings
• Tall R wave in V1
• prominent S waves in leads V5
and V6
• inverted T waves and ST
depression in V1 to V3
consistent with right ventricular
"strain," and
• peaked P waves in lead II
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18. Chest radiographic
• Enlargement of central pulmonary artery
• Peripheral vascular pruning
• Cardiomegaly
• Underlying cause and rule out differentials
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19. • Enlarged pulmonary arteries (black
arrows) and
• Pruning of the distal pulmonary
vasculature (white arrows)
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20. Cont..
• Prominence of the interstitial
pulmonary markings
• Enlargement of the right and left
ventricle and the right atrium (arrow).
• Large central, but attenuated
peripheral pulmonary arteries are
noted (arrowhead)
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21. Echocardiography
• Hypertrophied and dilated RV
• Elevated systolic PAP
• Etiologies (VHD,LV dysfunction, congenital abnormality intra cardiac shunt..)
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22. Cont…
Estimating pulmonary artery pressure
PASP = (4 x [TRV]2) + RAP
• PH is likely if the PASP is >50 and the TRV is >3.4
• PH is unlikely if the PASP is ≤36, the TRV is ≤2.8 and there are no other
suggestive findings
• PH is possible with other combinations of findings
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23. Cont…
• Right ventricular enlargement,
• Right ventricular hypertrophy,
• Right atrial enlargement,
• Functional tricuspid regurgitation with
a high velocity regurgitant jet by
Doppler (TR jet), and
• A mid-systolic notch on the pulmonary
artery Doppler flow tracing (PA flow)
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24. 11/06/2022 DR TEKIY 24

25. 11/06/2022 DR TEKIY 25

26. 11/06/2022 DR TEKIY 26

27. Pulmonary function tests
• Reduced diffuse capacity of lung for
carbon monoxide (DLCO)
• Obstructive Vs restrictive disease
• Overnight oximetry
• Nocturnal oxyhemoglobin
desaturation
Polysomnography
• Test for sleep related breathing
disorders
Ventilation-perfusion (V/Q )scan
• For chronic thromboembolic disease
CT pulmonary angiography
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28. Cont…
Exercise testing - six-minute walk test
• Degree of excertional hypoxia
• Detects exercised-induced PH
• Determines the patient's WHO functional class
• Establishes a baseline
• Provides prognostic information
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29. Right heart catheterization
• Confirm diagnosis of PH
• Distinguishing PH due to left heart disease
• Confirm presence and severity of a congenital or acquired left-to-right shunt
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30. Acute decompensated PHTN
• Sudden worsening of right heart failure
• systemic circulatory insufficiency and multi organ failure
• In-hospital mortality 14% to 100%
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31. RV dysfunctions
Echo
- Pericardial effusion, large right atrial
size, elevated right atrial pressure, or
septal shift during diastole
- Poor right ventricular contractile
- Low right ventricle fractional area
change & oxygen pulse during
exercise on stress echo
- Low right ventricular ejection
fraction <25%
- Increased N-terminal pro-brain
natriuretic peptide level (NT-
proBNP)
- Prolonged QRS duration
- Supraventricular arrhythmia
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32. Triggers for Acute decompensated PH
• Supraventricular arrhythmia
• Infection
• New thromboembolic event
• Drug discontinuation
• Salt diets
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33. Management principle
• Baseline severity assessment
• Primary therapy
• Secondary therapy
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34. Management cont…
• Supplemental oxygen
• Optimizing intravascular volume
• Augmenting RV function
• Maintaining coronary artery perfusion
• Decreasing RV afterload
• Treat precipitant
• Treat underlying cause
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35. Cont…
Intravascular volume
• Volume overload can cause RV dilation
and impaired left ventricular output
• Dynamic measures of volume
responsiveness unreliable
• Diuretics - with caution
• Ultrafiltration
Augment RV function
• Inotropic therapy
- Dobutamine 2–10
micrograms/kg/min or
- Milrinone 0.125–0.375
microgram/kg/min
This is RV failure without hypotension
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36. Decrease RV afterload
• Pulmonary vasodilators
-Prostanoids
-Endothelin receptor
antagonists
-Phosphodiesterase-5 inhibitors
Maintain right coronary artery perfusion
• Vasopressor therapy
- Norepinephrine 0.05–
0.75microgram/kg/min
- Avoid dopamine and phenylephrine
For RV and hypotensive PH
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37. Cont…
• For acute exacerbations of pulmonary
hypertension with RV failure
• Inhaled therapy
• Epoprostenol or nitric oxide
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38. Ventilatory and Mechanical support
• To maintain adequate oxygen delivery to all tissues while removing metabolic
waste
• Supplémental oxygen remains important in hypoxemia
• Patients with ARDS and chronic obstructive pulmonary disease can react
unfavorably to 100% oxygen
• Hypercapnia and acidemia also increase RV afterload and should be corrected to
near-normal levels if the overall ventilation strategy allows
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39. Cont…
• Functional residual capacity should be the target of lung volumes
• For ARDS with SEVER PHTN
• using an intermediate tidal volume (8 mL/kg)
• a PEEP below 10 mm H2O
• prone positioning, and
• low respiratory rate
• maintaining plateau pressure below 27 mm H2O
• PaCO2 below 60 mm Hg
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40. Cont…
• If RV failure and lung failure co-exist then
• an extracorporeal support, such as (VA-ECMO) or
• a right-sided tandem with oxygenator spliced in the circuit should be
considered
• If only RV support is needed, then an Impella device (Abiomed, Danvers, MA)
would be suitable
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41. Cont…
• For a longer duration surgically implanted RV assist device would be indicated
• In cases of biventricular failure
• bilateral Impella devices
• bilateral Tandems, or VA-ECMO are options for short-term support
• surgically implanted biventricular assist device for longer-term support
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42. Cont…
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43. Secondary therapy
Indication
• WHO functional class II, III, or
• IV PH despite adequate primary therapy
Patient selection
• Most group 1
• Avoid in group 2
• Group 3 only in sever PH when primary therapy
fail
• Group 4 - Not operative candidates
- As a bridge to surgery
- Suboptimal hemodynamic outcome
following thromboendarterectomy
• Group 5- selected patient
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44. Cont…
Agent selection
 WHO functional class
 Right ventricular function
 Hemodynamics
 Vasoreactivity test
 Patient characteristics and preferences
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45. Cont…
WHO functional class
• Class I - do not require pharmacologic therapy
• Class II & III - one or two oral agents
• Class IV - parenteral prostanoid
• Progressive or refractory disease -combination of two class
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46. Vasoreactivity test
• Identify those who may respond to calcium channel blockers (CCBs)
• Administer short-acting vasodilator then measure the hemodynamic response by
RHC
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47. Cont…
Indication
• Group 1 PAH (idiopathic, heritable, and
• anorexigen-induced PAH )
Contraindication
• low systemic blood pressure,
• low cardiac index
• severe (functional class IV) symptoms
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48. Cont…
• Agents used for vasoreactivity test
- Inhaled nitric oxide - 10 to 20 ppm
- Epoprostenol - 1 to 2 ng/kg per min
increase by 2 ng/kg/ min Q 5- 10 min
- adenosine - 50 mcg/kg/min increase Q 2min
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49. Cont…
Positive if all of the following
• mPAP decreases by >10 mmHg and below 40 mmHg
• Increased or unchanged cardiac output
• Minimally reduced or unchanged systemic BP
• Also PAP and PVR can be assesed
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50. Acute and long-term response
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51. Cont…
Overall theraputic agents
• Prostacyclin pathway agonists
• Endothelin receptor antagonists
• Nitric oxide (NO)-cGMP enhancers
• Calcium channel blockers
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52. The three target pathways
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53. 11/06/2022 DR TEKIY 53

54. Cont…
Calcium channel blockers
• Nifedipine -30 mg/d max 240mg/d
• Diltiazem - 120 mg/d max 900mg/d
• Amlodipine- 10mg/d max 20mg/d
Side effect
-Hypotension
-Worsen ventilation-perfusion mismatch and hypoxemia
-RV function deterioration
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55. Prostacyclin pathway agonists
• Epoprostenol- 1 to 2 ng/kg/min Continuous IV infusion via central venous
catheter
• Side effects
- Jaw pain, diarrhea, flushing, and arthralgias
- Thrombosis, pump malfunction ,interruption
of the infusion & catheter infection
• Agents of last resort
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56. Cont…
• Treprostinil
• 0.625 to 1.25 ng/kg/minute IV/SC
• 6 to 18 µg inhalation four times daily
• Iloprost
• 2.5 to 5 µg inhalation six to nine times
daily
• Selexipag
• 200 to 1600 µg PO twice daily
• The most effective in
• RV support and inotropic effect
• Agents for rescue therapy:
• RV failure,shock,pts presenting in FC IV
• A bridge for transplantation
• Portopulmonary PH,BE
• Best for patients CTEPH,prior to
interventions
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57. Cont…
Endothelin receptor antagonists
• Adverse effects hepatotoxicity and peripheral edema
• Nonselective and selective receptor antagonists
-Ambrisentan - 5 to 10 mg PO daily
-Bosentan - 62.5 to 125 mg PO two times daily
-Macitentan - 3 to 10 mg PO per day
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58. Cont…
Nitric oxide-cyclic guanosine monophosphate enhancers
• Phosphodiesterase type 5 inhibitors
- Sildenafil - 20 mg PO three times daily
- Tadalafil – 10mg IV three times daily
• Guanylate cyclase stimulant
- Riociguat
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59. Cont…
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60. Monotherapy vs combination therapy
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61. Monotherapy vs combination therapy
• According to the risk stratification low and medium
• Typical PAH:
Combination therapy (2 drugs [esp. PDE-5 inhibitor + ERA)
• Atypical PAH:
monotherapy
• Atypical PAH is defined as:
• age > 65 years
• arterial hypertension
• diabetes mellitus, obesity (BMI > 30 kg/m2 ) ◦ CHD, atrial fibrillation, enlarged
left atrium
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62. Pathway
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63. 11/06/2022 DR TEKIY 63

64. • RESULTS
• The primary analysis included 500 participants
• 253 were assigned to the combination-therapy group
• 126 to the ambrisentan-monotherapy group, and
• 121 to the tadalafil-monotherapy group.
• A primary end-point event occurred in 18%, 34%, and 28% of the
participants in these groups, respectively, and in 31% of the pooled
monotherapy group (the two monotherapy groups combined).
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65. • The hazard ratio for the primary end point in the combination-
therapy group versus the pooled-monotherapy group was
• 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001)
• At week 24, the combination-therapy group had greater reductions
from baseline in N-terminal pro–brain natriuretic peptide levels than
did the pooled-monotherapy group (mean change, −67.2% vs.
−50.4%; P<0.001),
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66. Results….
• Also higher percentage of patients with a satisfactory clinical response (39% vs.
29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P = 0.03)
• A greater improvement in the 6-minute walk distance (median change from
baseline, 48.98 m vs. 23.80 m; P<0.001)
• The adverse events that occurred more frequently in the combination-therapy
group than in either monotherapy group included peripheral edema, headache,
nasal congestion, and anemia.
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67. AMBITION TRIAL
• Combination therapy versus monotherapy for pulmonary arterial
hypertension
• Lajoie et al, Lancet Respir Med 2016
• meta-analysis (15 RCT, 4095 patients with pulmonary arterial
hypertension
• monotherapy - combination therapy
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68. • Results combination therapy
• significant improvement in WHO functional class
• significant improvement in walking distance
• significantly fewer PAH-related hospitalizations - significantly longer time to
clinical deterioration
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69. Cont…
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70. NATURAL HISTORY AND PROGNOSIS
• Group 1 PAH - worse survival
• Chronic thromboembolic- best survival
• Severe PH ( mPAP ≥35 mmHg) and evidence of right heart failure have a poor
prognosis.
• Median survival for PAH is 5–6 years
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71. Indication for long term oxygen therapy
Recommendation
• No evidence of LTOT survival benefits
• Idiopathic pulmonary hypertension, when PaO2 is ≤8 kPa. (Grade D)
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72. Special considerations
Pregnancy
• Maternal mortality rate, 30% to 50%
• Avoid Pregnancy if possible
• Avoid estrogen containing contraceptives
• Endothelin receptor antagonists and guanylate cyclase stimulants (riociguat) are
absolutely contraindicated
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73. Cont…
Patients requiring surgery
• High risk of CV collapse and death during anesthesia
• To minimize risk
- Avoid general anesthesia
- Treat decompensated right heart failure
-Optimize hemodynamics prior to elective surgery
-Prepare PA catheter monitoring, TEE , and inhaled NO in OR
-Perioperative management by multidisciplinary team
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74. Poor prognosis factors
• Age >50 years
• Male gender
• WHO functional class III or IV
• Failure to improve to a lower WHO
functional class during treatment
• Decreased pulmonary arterial
capacitance
• Hypocapnia
• Comorbid conditions (eg, COPD,
diabetes)
• PAH associated with connective tissue
disease
• Selective serotonin reuptake inhibitors
• Low von Willebrand factor levels
• Bone morphogenetic protein receptor
type 2 (BMPR2) mutations
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75. Cont…
Cause of death
• Right heart failure with circulatory collapse and superimposed
respiratory failure
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76. Discharge criteria
• Stable clinical status
• Must be on PO oral regimen for at least 24 hours
• Exacerbating factors addressed
• Volume status optimized
• Diuretic and chronic HF therapy changed to PO
• No IV vasodilator and inotropic therapy for at least 24 hours
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77. Advice
• Avoid heavy exercise
• Salt restricted diet <2.4gm/d
• Vaccination (influenza and pneumococcal
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78. References
• Scott LJ. Sitaxentan: In pulmonary arterial hypertension. Drugs. 2007;67(5):761–70.
• Galiè N, Barberà JA, Frost AE, Ghofrani H-A, Hoeper MM, McLaughlin V V., et al. Initial Use of
Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015;373(9):834–
44.
• 3 ‫غش‬1 ،
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‫عبمن‬ 2 ،
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‫تاثیر‬
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‫کربنات‬
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‫عملکرد‬
‫بی‬
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‫مردان‬
‫غیر‬
‫ورزشکار‬ .
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• Tintinalli, J., 2019. Tintinalli's Emergency Medicine: a Comprehensive Study Guide, 9th Edition.
9th ed. McGraw-Hill Education, pp.412-415
• 2014. Rosens emergency medicine. 9th ed. Philadelphia: Elsevier Saunders.
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79. End
Thank you
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