PULMONARY HYPERTENSION Flashcards
Definition of Pulmonary Hypertension?
The term “pulmonary hypertension” refers to the presence of a high pulmonary artery pressure that results from a variety of different disease processes involving the cardiovascular and pulmonary systems.
The current definition of PH includes the presence of an abnormally elevated mean pulmonary arterial pressure (mPAP; ≥20 mm Hg). Historically, PH was arbitrarily defined as an mPAP of ≥25 mm Hg measured in the supine position at rest during right heart catheterization.
Note: However, based on observations that the population resting mPAP is approximately 14 mm Hg, the new definition of PH was set at two standard deviations above the population mean (20 mm Hg) at the 2018 Sixth World Symposium on PH
Broadly pulmonary hypertension is divided into these two groups?
It is necessary to determine if PH is precapillary due to pulmonary vascular disease, postcapillary due to passive transmission of pressure from the left side of the heart, or a combination of the two. Pulmonary vascular resistance (PVR) has been added to the definition of precapillary PH to identify PH occurring as a result of pulmonary vascular disease.
Criteria for pre-capillary pulmonary hypertension?
PH: mPAP ≥20 mm Hg
Precapillary PH (groups 1, 3, 4, and 5): mPAP ≥20 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg, PVR ≥3 Wood units (WU)
Note: Pre-capillary is due to elevated pulmonary vascular resistence
Criteria for post-capillary pulmonary hypertension?
PH: mPAP ≥20 mm Hg
Postcapillary PH (groups 2 and 5): mPAP ≥20 mm Hg, PCWP ≥15 mm Hg, PVR ≤3 WU
Note: Post-capillary is due to transmission of elevated left sided filling pressures
Criteria for combined pre/post-capillary pulmonary hypertension?
PH: mPAP ≥20 mm Hg
Combined pre- and postcapillary (groups 2 and 5): mPAP ≥20 mm Hg, PCWP ≥15 mm Hg, PVR ≥3 WU
Group 1 pulmonary hypertension?
Group 1 pulmonary hypertension (pulmonary arterial hypertension) may be idiopathic, heritable, or associated with connective tissue disease, congenital heart disease, portal hypertension, or HIV.
PAH is in the range of 15-50 cases per million worldwide. PAH should not be considered a disease itself. Rather, it is the manifestation (elevated mPAP and PVR) of an underlying pulmonary vascular disease for which the etiology must be appropriately diagnosed.
Pulmonary arterial hypertension (PAH; group 1) is defined hemodynamically as an mPAP ≥20 mm Hg, a left heart filling pressure (PCWP, left ventricular end-diastolic pressure) ≤15 mm Hg, and a PVR ≥3 WU and requires the clinical exclusion of lung disease (group 3) and chronic thromboembolic pulmonary hypertension (CTEPH; group 4).
Causes of Group 1 pulmonary hypertension?
Causes of pulmonary arterial hypertension include:
- Idiopathic
- Heritable
- Toxin/drug induced
- Connective tissue disorders
- HIV
- Portal hypertension
- Congenital heart disease
- Schistosomiasis
Demographics & incidence of Group 1 idiopathic PAH?
Idiopathic pulmonary arterial hypertension (IPAH) is a sporadic, rare disease of unknown etiology. IPAH was historically referred to as primary PH. It is the most common type of group 1 PAH in current-day registries, representing approximately 50% of patients. There is a female preponderance (4:1 in REVEAL [Registry to Evaluate Early and Long-term PAH Disease Management]). The mean age at diagnosis in modern registries is about 50 years, although IPAH can affect children and adults into their 70s.
Genes associated with group 1 PAH?
Approximately 25% of patients diagnosed with IPAH are found to have genetic variations associated with heritable PAH. The most common genetic mutations occur in the bone morphogenetic protein receptor type 2 gene (BMPR2), a member of the transforming growth factor beta family. This mutation is autosomal dominant and characterized by incomplete penetrance and genetic anticipation.
Drugs and toxins associated with group 1 PAH?
The association between appetite suppressant drugs and PAH, then termed primary PH, was initially observed in the 1960s. Since then, several drugs and toxins have been identified that are associated with the development of PAH.
Notable drugs that have been linked to PAH include dasatinib, a tyrosine kinase inhibitor used to treat chronic myelogenous leukemia, and methamphetamines, an illicit drug that is the most common cause of drug- and toxin-induced PAH in the United States.
Connective tissue disorders associated with Group 1 PAH?
The prevalence of PAH is highest in those with the scleroderma spectrum of connective tissue diseases, occurring in approximately 10% of patients. Nonetheless, PAH can occur in the setting of any of the connective tissue diseases (e.g., systemic lupus erythematosus). Because scleroderma is a multisystem disease that can affect the heart and lungs, patients with scleroderma may also be at higher risk for group 2 PH from diastolic dysfunction and group 3 PH from hypoxemic lung disease. Systematic screening of scleroderma patients for PAH is recommended because of the high prevalence of the disease to promote earlier diagnosis and intervention.
HIV & Group 1 PAH?
The prevalence of PAH is approximately 0.5% among patients with HIV and is independent of the CD4 count. The mechanism is unknown but is suspected to be similar to IPAH, as the hemodynamics and clinical course are also indistinguishable. Routine screening for PAH in people with HIV is not recommended due to the low prevalence. PAH should be considered in the evaluation of HIV patients with dyspnea or fatigue.
Portal hypertension and Group 1 PAH?
The development of PAH in association with portal hypertension is known as “portopulmonary hypertension.” Although the condition most commonly occurs in the setting of portal hypertension from cirrhosis, the disease can occur as a result of noncirrhotic portal hypertension. The prevalence of PAH in individuals with portal hypertension is estimated to be approximately 2-6% in hemodynamic studies of patients being considered for a liver transplant. The mechanism is unknown. Echocardiography is used to screen for PAH in patients with symptoms or those undergoing workup for a liver transplant. Hemodynamic evaluation with right heart catheterization is necessary when PAH is suspected to differentiate portopulmonary hypertension from elevations in PAP that occur from the high-flow state of cirrhosis or high-output cardiac failure with elevated left heart filling pressures. The prognosis in portopulmonary hypertension is worse than in IPAH. Portopulmonary hypertension may be a contraindication to liver transplant if severe (mPAP >35 mm Hg) because of an associated increase in mortality.
Group 1 PAH and congential heart disease?
PAH can occur as a complication of uncorrected increased pulmonary blood flow associated with a congenital left-to-right intracardiac or extracardiac shunt. PAH associated with congenital heart disease is further classified into four subgroups: Eisenmenger syndrome, left-to-right shunts, coincidental or small defects, and postoperative/closed defects. Eisenmenger syndrome begins with an initial large systemic-to-pulmonary shunt (left-to-right) that induces progressive pulmonary vascular disease with PAH and subsequent reversal of the shunt (right-to-left) and central cyanosis. Eisenmenger syndrome usually occurs when the pulmonary vasculature is exposed to systemic level pressures as a result of shunts with high blood flow (e.g., ventricular septal defects, patent ductus arteriosus). PAH can also occur with low pressure shunts if the flow is high, such as with an atrial septal defect, or years after shunt closure, particularly if the closure was late.
Schistosomiasis and group 1 PAH?
PAH associated with schistosomiasis is a common cause of PAH in regions where schistosomiasis is endemic, including South America and sub-Saharan Africa. PAH associated with schistosomiasis has clinical and histologic features similar to IPAH.
Pathogenesis of Group 1 PAH?
Pulmonary arterial hypertension (PAH) is a syndrome resulting from restricted blood flow through the pulmonary circulation. PAH is a panvasculopathy predominantly affecting small pulmonary arteries (PAs) and is characterized by intimal hyperplasia, medial hypertrophy, adventitial proliferation, thrombosis in situ, and varying degrees of inflammation resulting in plexiform arteriopathy.
The PAH “phenotype” is characterized by endothelial dysfunction, a decreased ratio of apoptosis/proliferation in PA smooth muscle cells, and a thickened, disordered adventitia in which there is excessive activation of adventitial metalloproteases.
The PAH endothelium is characterized by increased production of vasoconstrictor/mitogenic compounds (e.g., endothelin and thromboxane) and reduced production of vasodilators (e.g., prostacyclin and nitric oxide). This imbalance favors vasoconstriction and signals smooth muscle cell activation, hyperplasia and hypertrophy, inhibition of apoptosis, fibroblast proliferation, collagen deposition, activation of proinflammatory cytokines, and angiogenesis.
Consequences of Group 1 PAH on the RV?
The ability of the right ventricle (RV) to cope with the increased pulmonary vascular resistance is a major determinant of functional capacity and prognosis in PAH. The RV initially responds to the increased afterload with myocardial hypertrophy. This adaptive response varies between individuals, with some compensating and others deteriorating over time, as manifested by RV dilatation and reduced ejection fraction, ultimately leading to RV failure and death.
Group 1 PAH and vasoreactivity testing?
PAH long-term responders to calcium channel blockers (CCBs) were added during the Sixth World Symposium in recognition of the unique clinical course, pathophysiology, management, and prognosis of the patients. PAH results from progressive remodeling of the pulmonary vasculature. Vasoconstriction of the pulmonary arteries is also thought to contribute to elevations in PVR to varying degrees for select patients. Vasoconstriction seems to have a prominent role among a subset of patients with PAH who respond to CCBs. Patients with IPAH, heritable PAH, or drug-induced PAH should undergo pulmonary vasoreactivity testing with either inhaled nitric oxide (preferred), intravenous epoprostenol, intravenous adenosine, or inhaled iloprost during right heart catheterization. Vasoreactivity testing is not recommended in other forms of PAH or PH, as patients are unlikely to be long-term responders. A response is considered positive if there is a reduction in mPAP by ≥10 mm Hg to an absolute value of ≤40 mm Hg without a decrease in cardiac output. A patient is considered a long-term responder if there is clinical improvement, defined as New York Heart Association (NYHA) functional class I or II, and sustained hemodynamic improvement after 1 year on CCBs.1 Patients who are long-term responders have an excellent prognosis.
What is group 2 pulmonary hypertension?
PH Group 2 occurs due to left heart disease occurs when left-sided ventricular or valvular dysfunction leads to chronic elevations in left atrial pressure, with the passive backward transmission of this pressure to the pulmonary vasculature.
Mortality in group 2 pulmonary hypertension patients?
PH occurring in the setting of left heart disease is associated with worse outcomes, including mortality, compared with patients with left heart disease without PH.
ECG findings of PH?
(RAE)
Right atrial enlargement produces a peaked P wave (P pulmonale) with amplitude:
> 2.5 mm in the inferior leads (II, III and AVF)
> 1.5 mm in V1 and V2
Note: In the EKG below we see P-waves greater than 2.5 mm in II, III and aVF (doesn’t need to be in all of these leads)
ECG findings of PH?
(RAE)
Normal P wave axis is between 0 and 75 degrees
Rightward shift of the P wave axis with prominent P waves in the inferior leads and flattened or inverted P waves in leads I and aVL
ECG findings of PH?
(RVH)
In this EKG we note:
Right axis deviation (+150 degrees).
Dominant R wave in V1 (> 7 mm tall; R/S ratio > 1)
Dominant S wave in V6 (> 7 mm deep; R/S ratio < 1).
Right ventricular strain pattern with ST depression and T-wave inversion in V1-4.
ECG findings of PH?
(RVH)
In this ECG we note:
Right axis deviation (+150 degrees)
P pulmonale (P wave in lead II > 2.5 mm)
Incomplete RBBB
Right ventricular strain pattern with T-wave inversion and ST depression in the right precordial (V1-3) and inferior (II, III, aVF) leads.
CXR in PH?
(Normal anatomy)
The right pulmonary artery gives off it’s first branch, the truncus anterior, The truncus anterior supplies the right upper lobe; and the interlobar artery, which runs in the interlobar fissure, supplies the right middle and right lower lobes.
The left main pulmonary artery has a long extra pericardial length before giving off its first branch. It continues as the common basal trunk and terminates in branches to the basal segments.
CXR in PH?
Normal anatomy :
1, right brachiocephalic vein; 2, superior vena cava; 3, aortic arch; 4, main pulmonary artery; 5, right upper lobe pulmonary artery; 6, left pulmonary artery; 7, Left atrial appendage; 8, right lower lobe pulmonary artery; 9, right atrium; 10, left ventricle; 11, inferior vena cava; 12, descending thoracic aorta.
CXR in PH?
CXR in PH?
(Pulmonary artery)
In PH we can see enlarged right descending pulmonary artery as well as enlargement of the pulmonary trunk
Note: A prominent main pulmonary artery, found just below and to the left of the aortic knob, is commonly seen in patients with PH. Elevated PA pressures have also been associated with enlargement of the right descending pulmonary artery (RDPA) and left descending pulmonary artery (LDPA).
CXR in PH?
(Right atrial enlargement)
The right atrial shadow (convexity in the lower half of the right mediastinal cardiovascular border) is usually:
not more than 50% of the cardiovascular height
CXR in PH?
(Right atrial enlargement)
The right atrial shadow (convexity in the lower half of the right mediastinal cardiovascular border) is usually:
not more than 5.5 cm from the midline
CXR in PH?
(Pulmonary trunk)
Oblique edge due to engorgement of the pulmonary artery (thin arrow)
CXR in PH?
(Hilum)
An absolute measurement of the hilum ≥112 mm was associated with a sensitivity of 82% in detecting elevated pulmonary artery systolic pressure. A ratio of hilum to chest diameter ≥0.44 had an even greater sensitivity of 86%
CXR in PH?
(RVH)
Lateral chest radiograph with fullness of the retrosternal space (arrow) commonly seen in right ventricular enlargement. Normal lateral chest radiograph provided on the right for comparison.
CXR in PH?
(Pruning)
The thinning out of vascular markings on a chest film also suggests elevation of pulmonary pressures and vascular remodeling, referred to as vascular pruning.
This is thought to be due to vascular remodeling of the pulmonary arteries
Frontal chest radiograph with plump pulmonary arteries seen coursing to the outer 1/3 of the lung with rapid tapering of vessels consistent with vascular pruning (arrows). The presence of vascular pruning is thought to be associated with vascular remodeling of the pulmonary arteries.
