B P9 C88 Pulmonary Hypertension

Question 1

Pathogenic remodeling of _____ pulmonary arterials increases pulmonary vascular resistance (PVR), which accompanies the hemodynamic pattern encountered in most PH patients clinically.

Answer 1

Medium and small pulmonary arteries

Question 2

Predominately, PH is caused by:

Answer 2

Left heart disease or parenchymal lung disease

Question 3

The pulmonary vascular circuit originates from the main pulmonary artery, which measures approximately _____ cm in diameter, and divides into the right and left main pulmonary arteries

Answer 3

2.7 to 2.9 cm

Question 4

By contrast, muscular pulmonary arteries and arterioles measure _____ μm and less than _____ μm in diameter, respectively, and are the principal structures affected in pulmonary circulatory diseases.

Answer 4

Pulmonary arteries: 100 to 500 um
Pulmonary arterioles: <100 um

Question 5

Alveolar capillaries measure _____ μm in diameter and are lined with a continuous layer of endothelium enveloped by pericytes at focal connections, but do not include pulmonary artery smooth cells and,thus,are noncontractile.

Answer 5

5-10 um

Question 6

The anatomy of the pulmonary vasculature is oriented in a _____ circuit, which permits high blood flow, low pressure, and low resistance

Answer 6

Parallel

Question 7

The systemic vasculature is organized as a circuit in _____ and designed to distribute cardiac output (CO) to regional beds

Answer 7

Series

Question 8

The _____ reflects the ratio of change in pulmonary artery pressure (ΔP) to mean pulmonary blood flow (Q) (L/min); when this value is multiplied by 80, the result is expressed as mm Hg/L/ min and referred to as a Wood unit (alternatively, resistance expressed as dyneseccm−5 divided by 80 yields a Wood unit)

Answer 8

PVR

Question 9

The calculated PVR may also be determined in clinical practice as:

Answer 9

PVR = (mean pulmonary artery pressure [mPAP]-left atrial pressure)/CO)

Question 10

Because routine left atrial sampling is not practical, the _____ is used as a surrogate of this measurement.

Answer 10

Pulmonary artery wedge pressure (PAWP)

Question 11

Beyond the age of 35 years, there is a gradual decline in extensibility of the conduit pulmonary arteries, and an increase in muscularization of medium and small vessels.This is characterized by _____, which, collectively causes mild fibrotic remodeling of the intima and vascular stiffening. The main pulmonary artery dilates slightly with age,

Answer 11

Collagen deposition and deterioration of elastin

Question 12

The average pulmonary blood flow at rest is _____ L/min/m2, and at any moment _____ mL/m2 of blood is in the pulmonary circulation of which approximately 25% occupies capillaries.

Answer 12

PBF at rest: 3.5 L/min/m2

Blood in pulmonary circulation: 300mL/m2

Question 13

The CO-mPAP relationship hinges on preserved distensibility, however, and pathological processes that impair normal pulmonary vascular compliance (even subtly) stand to disrupt cardiopulmonary physiology leading to a pathological state manifest by ______.

Answer 13

Impaired exercise tolerance

Question 14

There are two broad, inter-related strategies by which to classify patients with PH. First, the cardiopulmonary hemodynamic profile is used to assign patients into one of three categories:

Answer 14

Pre-capillary
Isolated post- capillary
Combined pre- and post-capillary PH

Question 15

Combined pre- and post- capillary PH refers to a post-capillary process that causes pulmonary arterial remodeling (indicated by increased ___)

Answer 15

PVR

Question 16

Hemodynamic characterisitics of pre-capillary PH

Answer 16

mPAP >20 mm Hg
PAWP ≤15 mm Hg
PVR ≥3WU

Question 17

Hemodynamic characteristics of isolated post-capillary PH (IpcPH)

Answer 17

mPAP >20 mm Hg
PAWP >15 mm Hg
PVR <3 WU

Question 18

Hemodynamic characteristics of Combined pre- and post-capillary PH (CpcPH)

Answer 18

mPAP >20 mm Hg
PAWP >15 mm Hg
PVR ≥3 WU

Question 19

Elevated mPAP > _____ mm Hg diagnosed by invasive right heart catheterization (RHC) measured supine at rest is the sine quo non of PH

Answer 19

> 20 mm Hg

Question 20

It is also important to note that the normal mPAP increases slightly with age and may be as high as ___ mm Hg among those greater than 50 years.

Answer 20

22 mm Hg

Question 21

PAWP greater than 15 mm Hg (or more conservatively >12 mm Hg) suggests _____, whereas PAWP ≤15 mm Hg (or ≤12 mm Hg) indicates _____.

Answer 21

> 15 mm Hg: pulmonary venous hypertension and post-capillary PH

≤15 mm Hg: pre-capillary PH

Question 22

If a direct LVEDP measurement is performed, greater than ___ mm Hg is generally used to diagnose post-capillary PH

Answer 22

> 15 mm Hg

Question 23

The most common form of PH that cardiologists will encounter in contemporary medical practice is in the setting of _____.

Answer 23

Left Heart Disease

Question 24

Processes that promote pathological remodeling of pulmonary arterials proximal to the lung capillary interface predispose patients to ______ PH

Answer 24

Pre-capillary PH

Question 25

Virtually any left heart structural or functional abnormality from the ascending aorta to pulmonary venous bed may predispose patients to _____ PH

Answer 25

Post-capillary PH

Question 26

Nonetheless, physiological or easily reversible causes of mPAP greater than 20 mm Hg have been reported, such as:

Answer 26

Anemia
Pregnancy
Increased pulmonary blood flow states (e.g.,highly conditioned athletes)

Question 27

_____ is used as a hemodynamic surrogate of pulmonary vascular disease, and the addition of this to mPAP increases the specificity of diagnosing PH compared to mPAP alone

Answer 27

PVR

Question 28

A cut-off PVR equal to or greater than ____ Wood units (WU) distinguishes pulmonary vascular disease in PH patients; however, this demarcation is largely historical or based on observational studies in selected subgroups, such as those with idiopathic PAH, congenital heart defects with intracardiac shunt, and pulmonary fibrosis

Answer 28

> 3.0 WU

Question 29

Combined pre- and post-capillary PH is an overlapping pathopheno- type that is characterized by pulmonary arterial remodeling due to chronic pulmonary venous hypertension, and in these patients _____ is used for diagnosis

Answer 29

mPAP greater than 20 mm Hg
PAWP greater than 15 mm Hg
PVR equal to or greater than 3.0 WU

Question 30

The prevalence of PH in HFrEF populations is 30% to 50% when considering a pulmonary artery systolic pressure (PASP) cut-off greater than ____ mm Hg estimated echocardiographically

Approximately 80% of HFpEF patients have PH (defined by an estimated PASP >35 mm Hg), which correlates with PAWP

In obstructive hypertrophic cardiomyopathy, PH is observed in over half of patients referred for anterior septal myectomy.

Answer 30

> 45 mm Hg

Question 31

Conversion method of Syyed: mPAP = ______

Answer 31

mPAP = 0.65 × PASP + 0.55 mm Hg

Question 32

Mitral stenosis patients with PASP greater than _____ mm Hg, for example, have a higher long-term rate of restenosis following mitral balloon valvuloplasty, and decreased 3-year survival following valvotomy compared to similar patients without severe PH

Answer 32

PASP > 60 mm Hg

Question 33

_____ variant is recognized as the most common genetic risk factor for PAH, identifiable in 70% of families with PAH and 10% of sporadic iPAH cases.

Answer 33

BMRP2

Question 34

The tyrosine kinase inhibitor _____ is associated with PAH, although this is unlikely a drug class effect.

Answer 34

Dasatinib

Methamphetamines may account for up to 18% of non-idiopathic PAH, but data on the true prevalence of this population are lacking. 30 Pulmonary vascular remodeling from a mechanical injury induced by the drug packing material or as a result of molecular interactions with drug metabolites

Question 35

Connective tissue disease-associated PAH accounts for approximately one in four cases of PAH overall, with _____ as the most common subtype.

Answer 35

Systemic Sclerosis (SSc)

Question 36

However, _____ is the leading cause of death in SSc, and the mortality rate is fourfold greater than for iPAH

Answer 36

PAH

Question 37

The actual prevalence of Schistosomiasis-PAH is not known, but this is undoubtedly the most common cause of _____ PH in developing countries.

Answer 37

Pre-capillary PH

The result is an immune complex hypersensitivity reaction (i.e., Katayama fever) which self-resolves over 4 to 6 weeks. However, the worms mate in the portal circulation and the eggs themselves are transported to the pulmonary vasculature where granulomatous remodeling ensues resulting in a PAH clinical syndrome.

Question 38

Within HIV populations, the odds ratio of increased pulmonary artery pressure is 1.27 and 1.28 in patients with viral load greater than ____ copies/mL and CD4 cell count less than _____ cells/μL, respectively, which is associated with a risk-adjusted mortality increase of 78%.

Answer 38

Viral load: >500 copies/mL
CD4 cell Ct: < 200 cells/uL

Question 39

Chronic PH is an uncommon manifestation of OSA, is almost always mild, and may be reversible with _____.

Answer 39

NIV

Question 40

Approximately 90% of COPD patients have mPAP greater than __ mm Hg, but only 5% have mPAP greater than 40 mm Hg

Answer 40

90%: > 20 mm Hg
5%: > 40 mm Hg

Thus, severe PH in COPD is uncommon but when present is a risk factor for cor pulmonale

Question 41

Thrombotic in situ pulmonary vascular remodeling resulting in PH occurs in approximately 3% of patients following luminal pulmonary embolism

Risk factors for developing CTEPH are not known, although elevated levels of _____ have been demonstrated in about 40% of patients.

Answer 41

Factor VII

Question 42

_____ are the cornerstone findings of pulmonary venoocclusive disease (PVOD)

Answer 42

Muscularization and sclerotic changes of pulmonary venules

Question 43

Risk factors for PVOD

Answer 43

Auto-immune disorders
Organic solvent exposure
Medical therapy with alkylating agents (particularly mitomycin and cyclophosphamide)
Certain genetic predispositions

Question 44

A positive test is defined by a:

Answer 44

Decrease in mPAP ≥10 mm Hg to reach an mPAP ≤40 mm Hg with a decrease (or no change) in CO

Question 45

In confrontational fluid challenge, a rise in PAWP to greater than _____ mm Hg is suggestive of pulmonary PH-left heart disease, although universally accepted diagnostic criteria remain lacking.

Answer 45

> 18 mm Hg

Question 46

________ are the fundamental components of invasive cardiopulmonary exercise testing (iCPET), which is useful for interrogating the pathophysiological basis of unexplained dyspnea.

Answer 46

Supine or upright cycle ergometry with a pulmonary artery catheter
Pneumotachograph
Radial artery catheter

Question 47

The over arching goal of therapy is to achieve the lowest risk level possible, which generally means:

Answer 47

(1) 6-MWD greater than 440 m or pVO2 greater than 15 mL/min/kg
(2) Right atrial area less than 18 cm2
(3) Cardiac index greater than 2.5 L/min/m2,
(4) Absent or low symptom burden with routine physical activity

Question 48

Patients with otherwise unexplained dyspnea that do not meet a hemodynamic classification of PH may bene- fit from exercise RHC or iCPET to unmask HFpEF or other etiologies as a cause of symptoms. In such patients, _____may be sufficient to avoid invasive testing, as the presence of these features point toward HFpEF.

Answer 48

Increased left atrial size greater than 4.4 cm
Obesity
Atrial fibrillation
Age greater than 60 years
Treatment with ≥2 anti-hypertensive drugs
Echocardiographic E/e′ ratio, or estimated PASP greater than 35 mm Hg

Question 49

In patients suspected of _____,a positive hemodynamic response to testing with iNO is diagnostic for vasoreactive PAH (although a negative response does not exclude PAH)

Answer 49

Idiopathic
Hereditary
Drug/toxin PAH

Question 50

This is defined as portal hypertension with pre-capillary PH and PVR equal to or greater than 3.0 WU

Answer 50

Portopulmonary hypertension

The detrimental effects of high CO and endotoxin release from liver dysfunction

Question 51

This is defined as hypoxemia from intrapulmonary vasodilation and impaired hypoxic vasoconstriction (without PH)

Answer 51

Hepatopulmonary syndrome

Question 52

All forms of persistent PH are associated with pathogenic vascular remodeling, and most subtypes involve hypertrophic concentric muscularization, as well as fibrotic and (micro) thrombotic effacement of distal pulmonary arterials

The ____ are usually phenotypically normal.

Answer 52

Main-, lobar-, and intra-lobar pulmonary arteries

Exceptions - proximal pulmonary arterial involvement in patients with CTEPH.

Question 53

Unique plexogenic vasculopathy seen in what conditions?

These focal but dense lesions are characterized by endothelial proliferation, the formation of microchannel networks, and irregular smooth muscle cell orientation in a glomeruloid pattern.

Answer 53

In iPAH, certain forms of congenital heart disease, HIV-PAH, and Schistosomiasis-PAH

Question 54

Pulmonary venous remodeling is a classic feature of ______

Answer 54

PVOD

A rare form of PH that overlaps histopathologically with pulmonary capillary hemangiomatosis (PCH). In both PVOD and PCH, arterial medial hypertrophy and/or intimal fibrosis, hemosiderosis, venulitis, and mild lymphocytic infiltrate are observed.

In PVOD, obliteration of small pulmonary veins occurs due to sclerotic and fibrous thickening.

Question 55

Organized clot, defined by heavily fibrotic and obstructive lesions involving the intima and medial layers of distal pulmonary arterials, is a cornerstone feature of _______

Answer 55

CTEPH

Question 56

The pulmonary vascular bed is a parallel circuit densely packed with blood vessels, evolved to maximize surface area for gas exchange at the alveolar interface. It is therefor a _____

Answer 56

High-flow, low-resistance system

Question 57

It is important to recognize that pressure in the pulmonary circuit is determined, in part, by _____

Answer 57

RV contractility

If RV failure is present, pulmonary artery pressure may be only mildly elevated

Question 58

Secondary manifestations of PH

Answer 58

Chronic renal failure, leaky bowel syndrome, volitional muscle atrophy including diaphragmatic weakness, and cognitive impairment, or passive hepatic congestion due to elevated right atrial pressure

Question 59

High-risk presenting symptoms that are equivalent to a PAH emergency

Answer 59

Cardiac angina (due to either RV ischemia or left main coronary artery compression)
Syncope (due to severely decreased CO)

Question 60

PE findings of right-sided pressure and volume overload

Answer 60

A loud or paradoxical P2 component of the second heart sound indicates accentuation of pulmonic closure. In severe PH, right-sided S3, RV lift, increased jugular venous pressure, and pulsatile liver may be observed

Question 61

ECG findings in PH

Answer 61

Right atrial enlargement or RV hypertrophy, which is suggested by an R/S ratio greater than 1 in lead V1 without other causes, or if the R wave amplitude in lead V1 is greater than 7 mm

An RV strain pattern (defined by RV hypertrophy with ST segment depression in V1 to V3) may be evident in advanced disease stages.

Question 62

CXR findings in PH

Answer 62

Central pulmonary artery dilation, peripheral dearborization, right atrial and RV enlargement

Question 63

Echo findings in PH

Answer 63

Question 64

______ is recommended in all patients suspected of PH

Answer 64

Pulmonary function test with spirometry and lung diffusion capacity of carbon monoxide (DLCO)

Question 65

______ on ventilation-perfusion (V/Q) scintigraphy is highly suggestive of CTEPH

Answer 65

Mismatched perfusion defects

Question 66

A positive vasoreactivity test is defined by ____

Answer 66

A decrease in mPAP ≥10 mm Hg to reach an mPAP ≤40 mm Hg with a decrease (or no change) in CO,

Question 67

Confrontational fluid challenge in differentiating PAH from PH-Left Heart Disease

In these circumstances, monitoring a change in PAWP following the administration of 500 mL normal saline over 5 min may be useful for eliciting occult LV lusitropic impairment to uncover PH.

Result suggestive of Left Heart Disease?

Answer 67

A rise in PAWP to greater than 18 mm Hg is suggestive of pulmonary PH-left heart disease,

Question 68

The overarching goal of therapy in PH is to achieve the lowest risk level possible, which generally means:

Answer 68

6-MWD greater than 440 m
pVO2 greater than 15 mL/min/kg
Right atrial area less than 18 cm2
Cardiac index greater than 2.5 L/min/m2
Absent or low symptom burden with routine physical activity

Question 69

Probability of PH using TR jet

Answer 69

Question 70

Integrated pathway for diagnosing pulmonary hypertension

Answer 70

Question 71

A diagnosis of CTEPH must be suspected in any patient with _____ and otherwise unexplained dyspnea or PH

Answer 71

Prior PE

Question 72

Indications for continuous parenteral prostacyclin therapy

Answer 72

New York Heart Association Functional Class (NYHA FC) IV
Cardiogenic shock by clinical or hemodynamic criteria (e.g., signs of impaired distal perfusion, cardiac index <2.1 l/min/ m2)
Syncope
Chest pain (indicative of either RV ischemia or LMCA compression)

Question 73

For patients with a positive vasoreactivity test, ______ is the initial treatment in the absence of high-risk findings.

Answer 73

High-dose calcium channel antagonist therapy

Question 74

Upon diagnosing CTEPH, all patients should be considered for ____

Answer 74

Surgical pulmonary thromboendarterectomy

Surgery provides a distinct survival advantage and opportunity for complete or near complete resolution of symptoms

Question 75

Factors to consider in surgical pulmonary endarterectomy

Answer 75

Proximal vs. distal clot
Comorbidities
PVR >12 WU
Right heart failure
NYHA FC IV

Question 76

In patients that are poor surgical candidates, have inoperable disease, or decline surgery, _____ at an expert referral center is a modern-day treatment option

Answer 76

Percutaneous balloon pulmonary angioplasty (BPA)

Question 77

In heart transplantation, PVR greater than ____ and transpulmonary gradient greater than _____ is a relative contra-indication to heart transplantation

Answer 77

PVR > 5 WU

TPG > 16 mm Hg

Acute vasodilator challenge should be performed if sPAP greater than 50 mm Hg, and either transpulmonary gradient ≥15 mm Hg (calculated by: mPAP − PAWP) or PVR greater than 3 WU and systemic systolic arterial pressure greater than 85 mm H

Question 78

At high altitude, particularly but not exclusively ≥2500 m

A fall in _____ (measured as the partial pressure of O2) detected at the level of the alveolar capillary is a major trigger of hypoxic pulmonary vasoconstriction

Answer 78

Oxygen tension

Question 79

Inhomogeneous hypoxic pulmonary vasoconstriction associated with rapid ascent causes ____ arising from changes in capillary membrane permeability that lead to exudative effusion

Answer 79

High-altitude pulmonary edema (HAPE)

Question 80

The PH typical of high altitude is generally mild and tolerated clinically.

In patients with high-altitude PH, descent to lower altitude is important and may be lifesaving when the syndrome is complicated by heart failure.

____ and _____ therapies have also been reported effective at improving PH severity.

Answer 80

PDE-V inhibitor and acetazolamide

Question 81

____ is an established aspect of the sickle cell disease spectrum, affecting approximately 30% of patients.

Answer 81

Pre-capillary PH

Therapy for sickle cell disease-PH should focus on correcting underlying anemia with hydroxyurea and blood transfusion. PDE-V inhibitor therapy may improve cardiopulmonary hemodynamics in this population but increases sickle cell vasoocclusive pain, and, therefore, should not be considered outside the advice and management of an expert referral center.67

Question 82

Mortality or heart failure requiring lung transplantation is reported in ___ of pregnant women with PAH

Answer 82

20%

Question 83

For PAH patients, _____ should be avoided when possible. In patients requiring general anesthesia, an individualized care plan including cardiac anesthesia, intraoperative pulmonary artery catheter monitoring, and a plan to use inhaled therapies may prove useful.

Answer 83

General anesthesia