Peripheral Pulmonary Stenosis

Peripheral Pulmonary StenosisByDr. Varun K.

Isolated peripheral pulmonary artery stenosis was described first by Maugars and later by Schwalbe

Stenosis of the pulmonary arteries, isolated or in association with other cardiac defects, occurs in 2% to 3% of all patients with congenital heart disease.

The stenosis may be single, involving the main pulmonary artery or either of its branches, or multiple, involving both the main and several smaller peripheral pulmonary artery branches

Other associated cardiac defects, most commonly valvar PS and VSD, are present in about 2/3rd of the cases.

Hypoplasia of the pulmonary arteries also is seen frequently with TOF

In congenital rubella syndrome, peripheral pulmonary artery stenosis typically is associated with PDA and ASD.

In Williams syndrome, multiple peripheral pulmonary artery stenosis, supravalvar AS, mental retardation, and peculiar facies

associated with Noonan syndrome, Alagille syndrome, cutis laxa, Ehler Danlos syndrome, and Silver Russell syndrome.

Pulmonary artery stenosis (PAS) is the second most common CV abnormality in WS

The incidence of PAS in WS depends on the age at the time of presentation

More common in patients in the first year of life than at older ages

The reported range of incidence of PAS in WS is 37- 75%, with the majority of studies reporting an incidence of 40%

The stenoses seen in the pulmonary arterial bed most commonly occur in the branch and peripheral PA

Embryology and Pathology

The proximal portion of the MPA - bulbus cordis.

The remainder of the trunk of the MPA - common truncus arteriosus.

The proximal segments of the RPA and LPA - 6th branchial arches on either side.

The distal portion of the left 6th arch persists as the ductus arteriosus and later as the ligamentum arteriosus.

The peripheral portions of the PA branches derive from the postbranchial pulmonary vascular plexus, which lies in close relationship to the growing lung buds.

The rubella virus, appears to exert its teratogenic effect by interfering with the normal formation of the elastic tissues.

Williams syndrome - A genetic deletion mapped to chr. 7 resulting in abnormal elastin production

Alagille syndrome - Mutations in either JAG1 or NOTCH2 have mapped to the chr.20. JAG1, which encodes a ligand critical to the notch genesignaling cascade that is important in fetal development

Noonan's syndrome - associated with mutations in genes on chr.12 that are part of the RAS/RAF/MEK/ERK signal transduction pathway, an important regulator of cell growth. Approximately 50% of patients have gene mutations inPTPN11

Sporadic or can be familial with AD inheritance.

Classification A useful classification was proposed by Gay et al. They classified the stenoses into four types:

stenoses involving the main pulmonary trunk or the right and left branches,

stenoses involving the bifurcation of the pulmonary artery extending into both branches,

multiple peripheral stenoses,

a combination of main and peripheral stenoses

Physiology Elevated RV and PA (proximal to stenosis) systolic pressure that depends on the severity and distribution of the stenoses

When the obstruction is severe, RV ejection is prolonged and the PA trunk proximal to the obstruction behaves as an extension of the RVOT.

The pressure tracing proximal to the stenosis resembles that of the RV, with high systolic and low diastolic pressure

When the stenosis is U/L and there is no left-to-right shunt, resting RV pressure remains normal

Because flow to the stenotic side is lower than normal, the systolic pressure difference tends to underestimate the severity of obstruction; however, the diastolic pressure difference between the main pulmonary artery and the stenotic branch is proportional to the severity of obstruction.

Clinical featuresPts. with mild or moderate bilateral PA stenosis, as well as those with unilateral stenosis, are usually asymptomatic

DOE, easy fatigability, and signs of right heart failure may occur in patients with severe obstruction.

Children and adults occasionally experience chest pain

Haemoptysis

Sudden death

S1 is usually normal, and there is no ejection click.

S2 is usually normally split and P2 is of normal intensity

Systolic crescendo-decrescendo murmur with delayed onset in the pulmonary area that is well transmitted to the axilla and back.

A continuous murmur occasionally may be present, indicating that the diastolic gradient across the obstruction is significant.

The presence of soft, blowing systolic or continuous murmurs typically heard over both lung fields and in the back should point to the correct diagnosis.

Ecg The ECG is normal in patients with mild stenosis and demonstrates RVH in those with moderate to severe obstruction.

A relatively high frequency of LAD has been noted in infants with the rubella syndrome, as well as in infants with Noonan syndrome.

Radiologic features Only in cases of severe unilateral stenosis and increased pulmonary blood flow is there a detectable difference in the degree of vascularity between the two lung fields.

When the stenosis is bilateral and severe, RA and RV enlargement may be seen.

MRI is becoming increasingly useful in detailing PA anatomy. It is superior to echocardiography and complementary to angiography for the detection of pulmonary artery abnormalities.

Radionuclide lung perfusion scans are very useful in quantifying flow to each lung before and after surgical or transcatheter therapy

Echocardiographic featuresThe anatomy of the proximal PA usually can be delineated fairly well, but the distal PA cannot be imaged reliably. The PSAX view and suprasternal views are the most helpful.

Color flow Doppler can contribute to the qualitative assessment of stenosis by the appearance of turbulence at the area of obstruction. The pressure gradient can be estimated by Doppler but not always accurately.

The echocardiogram is useful in detecting secondary manifestations of RV hypertension, such as RVH, TR, or enlargement of the right-sided chambers.

Cardiac catheterizationThe clinical suspicion of peripheral pulmonary stenosis usually requires cardiac catheterization to confirm the diagnosis as well as to determine the severity and exact anatomy.

Carefully obtained withdrawal pressure tracings from the distal branches will demonstrate pressure gradients across the stenotic segments.

Systolic pressure gradients >10 mm Hg should be considered abnormal in the absence of increased pulmonary blood flow

When the stenosis is unilateral, a pressure gradient is present at the site of obstruction, but the proximal PA pressure is normal. The measured gradient may underestimate the severity of angiographic obstruction as a result of preferential flow to the unobstructed side

With bilateral PA stenosis, the systolic portion of the tracing is identical to that of the RV. The dicrotic notch is usually quite low with a slow descent, followed by low diastolic pressure similar to that distal to the obstruction.

Angiography Angiocardiography is the best tool in the diagnosis of peripheral PA stenosis.

The exact location, extent, and distribution of the lesions can be easily visualized with selective injections proximal to the site of obstruction.

The anterior view with cranial angulation and straight lateral views usually show the anatomy of the RPA and of the peripheral branches bilaterally. The proximal LPA can be well visualized in the hemiaxial oblique views

Non invasive imaging : MRI and CTGadolinium-enhanced three-dimensional magnetic resonance angiography (MRA) has been shown to correlate with angiographic findings with 100% sensitivity and specificity when assessing PA stenosis or hypoplasia, absent or discontinuous PA.

Measurements of PA diameter also showed excellent correlation, with a mean difference of 0.5 mm 1.5 mm between the two modalities.

A limitation of MRA for pediatric patients is motion artifact requiring breath holding for optimal image acquisition.

Anatomic delineation of the more peripheral branches, typically beyond the 3rd and 4th generation is not adequately achieved by MRA.

Advantages include reduced risk, avoidance of radiation, and preservation of vascular access for future interventional procedures.

Electron-beam computed tomography (CT) has also shown excellent correlation with angiography . It is less sensitive to motion artifact and can often be performed with sedation alone, even in small infants.

CT is more suited for the unstable patient because of the short time needed to acquire the information and has better spatial resolution than MRA.

Radiation exposure and contrast administration are necessary, but the dose of both is typically lower than needed for angiography to obtain the same information.

Exact hemodynamic measurements still require cardiac catheterization.

Treatment Mild to moderate isolated unilateral or bilateral peripheral pulmonary artery stenosis usually does not require treatment

Despite significant improvements in surgical techniques, access to distal vessels remains difficult, and catheter treatment is sometimes the only option.

Balloon angioplastyThe first use of PTA for peripheral pulmonary arterial stenosis was described by Martin et al. in 1980

investigators demonstrated histologically that successful dilations resulted from intimal and medial tearing of the pulmonary artery wall

The protocol for angioplasty consists of positioning a balloon dilation catheter across the stenotic segment of the pulmonary artery.

The balloon diameter should be 3-4 times the narrowest PA segment.

Initially, the balloon is inflated to low pressure (1 to 2 atm) while confirming proper position, indicated by a waist representing the stenotic segment centered on the balloon.

Under continuous fluoroscopic monitoring, the balloon is inflated further to higher pressure for a variable period (10 to 60 seconds) until the waist disappears or the maximum pressure is reached.

A postdilation angiogram should be performed either just proximal to the dilated area or by advancing an end-hole angiographic catheter over a guidewire left in place across the dilated segment

Percutaneous balloon angioplasty of peripheral pulmonary artery stenosis has met with a significantly lower success rate than pulmonary valvuloplasty.

The criteria used to determine success has been described arbitrarily as an increase of >50% in vessel diameter, an increase of >20% in flow to the affected lung, or a decrease of >20% in systolic RV to aortic pressure ratio.

The overall acute success rate for patients with varying diagnoses, most commonly TOF with and without pulmonary atresia, has been reported as 50-60% and appears to be similar in the small subset of patients with isolated peripheral pulmonary artery stenosis and intact ventricular septum.

Hosking et al. examined the clinical impact of balloon angioplasty using relatively low pressure balloons on subsequent management and found that only 35% of patients were favorably influenced by the procedure, with no patient previously considered inoperable becoming operable following angioplasty.

A similar study by Zeevi et al. found a 50% rate of favorable clinical impact using more stringent criteria for technical success and high-pressure balloons on some patients.

The rate of recurrent stenosis has been 15-20% in short-term to midterm follow-up; long-term follow-up is unknown.

Because of the disappointing results obtained with low-pressure balloons, high-pressure balloons that can be inflated 20 to 25 atm are being used increasingly to dilate PA. The overall acute success rate is around 70-80%, but still only 50% in patients with isolated peripheral pulmonary artery stenosis.

Limited information is available regarding the frequency of restenosis, but it may be higher than had been previously suspected.

Using high-pressure balloons whenever necessary, and defining restenosis as >50% decrease in the gain in diameter achieved at the initial successful angioplasty, a restenosis rate of 35% was found at follow-up angiography in a group of 48 patients by Bush et al

The continued effort to improve on the success rate of balloon angioplasty for resistant pulmonary artery stenosis has recently brought about the use of cutting balloons in this setting.

These balloons have 3-4 microsurgical blades with a cutting depth of 0.15 mm mounted longitudinally at 90-degree angles to the balloon.

The technique is best suited for small, lobar pulmonary artery branches not amenable to stenting.

Vessels resistant to high-pressure balloon angioplasty have been shown to respond to either cutting balloon angioplasty alone, or cutting balloon angioplasty followed by high-pressure ballooning.

The longitudinal cuts made by the blades create sites for the tear to propagate when further dilated with a high-pressure balloon. Successful dilation has been achieved in 92% of resistant vessels in a study by Bergersen et al

Significant complications have been reported in 5-15% of patients following percutaneous balloon dilation of peripheral pulmonary arterial stenosis.

These complications include exsanguination from a ruptured PA either by the dilating balloon or the guidewire hemoptysisipsilateral pulmonary edemaobstruction of dilated vessels by intimal flapspulmonary artery aneurysmsclotted iliac veinsTransient arrhythmias, cyanosis, and hypotension also may occur during pulmonary artery angioplasty

Transcatheter intervention is most commonly used for peripheral PAS

Geggel et al have reported that central PA do not respond well to balloon angioplasty. However, the intrapulmonary segments of the PA respond better to balloon dilation, especially when undertaken in a serial manner.

Wessel et al previously reported that high degrees of PAS are tolerated well without intervention, which, when combined with the high frequency of complications from transcatheter interventions ( PA aneurysm) led Geggel et al to recommend frequent noninvasive observation in the asymptomatic patient with subsystemic RV pressures. Rapid failure of arterial stenting in patients with WS has been reported

In-stent stenosis in patients with WS is likely related to an abnormal arterial response to injury caused by stent implantation in the setting of decreased arterial elastin.

The mortality rate, measured at 7.7% in one series by Geggel et al, is more than twice that reported in other settings.

Interestingly, the cause of death was not associated with PA trauma in any of the patients in this study, but rather, occurred in patients with significant coronary artery stenosis or ventricular hypertrophy and concomitant subendocardial ischemia with transient hemodynamic perturbations.

These findings, coupled with the recognition that spontaneous improvement is often seen in patients with Williams syndrome and pulmonary artery stenosis, have led most investigators to recommend watchful waiting, particularly in young, asymptomatic children, despite significant elevation of the right ventricular pressure.

When necessary, a combined approach with distal balloon angioplasty and proximal surgical reconstruction may be the best therapy in this difficult group of patients

Balloon-expandable intravascular stentsThe stainless steel balloon-expandable stent developed by Palmaz et al. dramatically improved the effectiveness of balloon angioplasty in a selected group of patients

Several investigators reported excellent results acutely as well as in midterm follow-up of stent implantation for pulmonary artery stenosis, with an increase of >100% in stenosis diameter and a >75% reduction in gradient. Most of the patients in these studies had associated congenital heart disease, such as TOF with and without pulmonary atresia and TA, and a smaller number had isolated congenital pulmonary artery stenosis

Shaffer et al reported on a group of 15 patients with isolated PAS. There was a dramatic immediate decrease in the gradient across the stenotic areas but a less significant decrease in RV pressure than seen in the rest of the group, as well as an increase in the RV pressure at midterm follow-up not seen in the other patients.

Complications from stent implantation include

incorrect stent positioning or embolization, sometimes requiring surgical removal

thrombosis of the pulmonary artery within the stent

all the complications associated with balloon angioplasty alone, including pulmonary edema and pulmonary hemorrhage

At follow-up catheterization, a small and usually hemodynamically insignificant decrease in diameter of the stented vessel has been noted that resulted from neointimal proliferation.

McMahon et al noted an increase in luminal diameter from 5.4 mm to 11.2 mm immediately after stent placement and a decrease to 9.3 mm after 5.6 years of mean follow-up.

More significant narrowings can develop in areas of diameter mismatch between the stented and nonstented vessel, or in between nonoverlapping serial stents.

In most cases the gradient measured on follow-up was due to growth of the vessel wall adjacent to the stent despite the absence of significant restenosis within the stent

In very small patients, stents should be avoided unless the stent used has the capacity to later be enlarged to adult diameter. For older children and adult patients, in whom stents can be dilated at the initial or subsequent catheterizations to the required adult size of the vessel, stent placement has become the preferred therapy for refractory branch pulmonary stenosis

Surgery Multiple peripheral stenoses were first tackled by McGoon et al. using an azygous vein graft to patch over the incised stenotic segments

Further surgical experience with PA reconstruction was gained primarily in patients with TOF with pulmonary atresia and aortopulmonary collateral arteries.

When native arterioplasty is not sufficient, stenotic segments are enlarged, preferably with autologous pericardium and occasionally with azygous vein grafts

Isolated congenital peripheral PA stenosis, often accompanied by long-segment hypoplasia, is difficult to treat successfully with either balloon angioplasty or surgery.

Various techniques are used to deal with this lesion, including excision of stenotic segments, and use of an autologous pericardial roll to restore arterial continuity when direct anastomosis is not possible

A combined approach, with surgical reconstruction followed by transcatheter pulmonary artery intervention, is often the best form of treatment.

Course and prognosisRoutine prophylaxis against endocarditis in acyanotic patients with untreated peripheral pulmonary stenosis is not recommended.

Endocarditis prophylaxis is recommended for patients who have received prosthetic material to treat pulmonary artery stenosis, whether placed by surgery or by catheter intervention, during the first six months after the procedure

Most patients with mild or moderate stenosis remain stable, and pressure gradients recorded early in life often decrease with growth. This is particularly true in patients with associated syndromes, such as Williams, Noonan, or congenital rubella

However, multiple peripheral pulmonary stenosis of severe degree may be progressive, and the prognosis is poor unless angioplasty, stent placement, or surgery is successful

Complications include

right ventricular failurepulmonary artery thrombosispoststenotic aneurysmal dilation with pulmonary artery hemorrhage

Isolated peripheral pulmonary artery stenosis is rarely seen in adult patients and often is misdiagnosed as chronic pulmonary thromboembolic disease. These patients typically present with exertional dyspnea and fatigue, and symptomatic improvement has been seen following balloon angioplasty.

Systemic vasculitis with pulmonary arterial involvement should be excluded.

The presence of murmurs consistent with pulmonary artery stenosis in many of these patients in childhood or adolescence suggests a congenital cause with slow progression.

Thank you