Imaging of Pulmonary Vascular Disease by Intravascular Ultrasound

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International Journal of Cardiac Imaging 9: 179-184,1993. @ 1993 Kluwer Academic Publishers. Printed in the Netherlands.

Imaging of pulmonary vascular disease by intravascular ultrasound

Peter John Scott,1 Ahmed Rashid Essop, 1Waddah A1-Ashab, ~Andrew Deaner, 1Johnathan Parsons 2 & Gordon Williamsl ~Non-Invasive Heart Unit, 2Department of Paediatric Cardiology, Killingbeck Hospital, Leeds, West Yorkshire, UK (*corresponding address) Dept of Cardiology, Leeds General Infirmary, Great George Street, Leeds, West Yorkshire LSI 3EX, UK

Accepted 4 January1993

Key words: pulmonary vascular disease, intravascular ultrasound

Abstract

To assess the ability of intravascular ultrasound (IVUS) to image changes in the pulmonary arterial wall associated with pulmonary hypertension (PHT), 10 subjects requiring diagnostic right and left heart catheterization were studied. In addition to measurements of pulmonary artery pressure and pulmonary vascular resistance and pulmonary angiography, when indicated, all underwent simultaneous IVUS imaging in the pulmonary arterial system using a 20MHz ultrasound transducer mounted on a 2 mm diameter catheter. Four patients had normal pulmonary artery pressures and 6 had varying degrees of PHT. Satisfactory ultrasound images were obtained in 9 out of the 10 patients. In those with normal pulmonary artery pressures ultrasound showed a thin vessel wall with no destinction between separate layers. In patients with systemic PHT, a three- layered vessel wall was apparent and areas compatible with intimal proliferation were seen. In a patient with pulmonary embolic disease areas consistent with mural thrombus were detected at sites of luminal narrowing on the pulmonary angiogram. IVUS is capable of imaging some of the morphological changes in the wall of the pulmonary artery known to occur in longstanding PHT and may therefore become a useful adjunct to haemodynamicmeasurements and pulmonary angiography for the in vivo assessement of pulmonaryvascular disease.

Abbreviations: IVUS - intravascular ultrasound, PHT - pulmonary hypertension

Introduction ripheral arterial circulations and can be either wire guided or free-floating. Some catheters employ Intravascular ultrasound (IVUS) is one of the latest phased array transducers with up to 64 elements. imaging techniques and is a novel method for as- Promising work has been performed using the sessing atherosclerotic arterial disease that has ma- catheters for intracardiac imaging including the as- jor advantages over contrast angiography [1]. Most sessment of atrial septal defects [2] and aortic valve IVUS catheters incorporate a mechanically driven stenosis [3] but practical applications for this re- ultrasound transducer operating at frequencies main to be established. Imaging of proximal and ranging from 10 to 30 MHz, the most commonly em- distal pulmonary arteries in both animals and nor- ployed being 20MHz. The catheters are small mal human subjects has proved successful using a enough to be passed safely in the coronary and pe- 20MHz intravascular ultrasound transducer [4]. 180

To evaluate the potential of IVUS for imaging cular resistances whilst the remainder all had signif- morphological changes in the pulmonary arterial icant PHT with raised pulmonary vascular resist- wall associated with chronic pulmonary hyperten- ances due to a variety of causes. sion (PHT), we studied 10 patients undergoing rou- tine diagnostic right and left heart catheterization. lntravascular ultrasound Four had normal pulmonary artery pressures and 6 This was performed with a 20MHz transducer, me- had significant PHT due to a variety of causes. chanically rotated in a 6 French (2ram) diameter sterile sheath (Boston Scientific) (Fig. 1) which was connected to a Diasonics ultrasound machine. The Patients and methods total length of the ultrasound catheter was 100cm. On completion of the right heart catheter study, the Over a six month period 10 patients requiring clin- diagnostic catheter was exchanged over a guide ically indicated cardiac catheterization underwent wire for a bioptome guiding sheath whose tip was simultaneous IVUS imaging in the pulmonary arte- positioned distally in one of the main pulmonary ar- rial circulation. Their clinical details are summar- tery branches. The ultrasound catheter was then ised in Table 1. All patients were clinically stable passed along the bioptome guiding sheath and its prior to the study which was performed either as an tip advanced to the periphery of the lung (Fig. 2), initial diagnostic catheter study or as part of a work- into a wedge position. Ultrasound images were then up for cardiac or cardiopulmonary transplantation. recorded as the catheter and transducer were with- drawn into the main pulmonary artery. The catheter Cardiac catheterization was readvanced into a different pulmonary artery All catheter procedures were performed via right branch so that a number of branches from each lung femoral arterial and venous punctures. Right and could be studied. A mean of 6 studies were made in left heart pressures were measured with standard each patient. catheters and pulmonary vascular resistance was calculated after estimation of the cardiac output from measured oxygen uptake. Pulmonary angio- Results graphy was performed when indicated (n = 2). Four had normal pulmonary arterial pressures and vas- The pulmonary artery pressures and pulmonary

Table 1. Clinical details and haemodynamicfindings of the study patients.

Patient Age Diagnosis SystolicPAP MeanPAP SystolicSAP MeanSAP Pulmonary (mmHg) (mmHg) (mmHg) (mmHg) resistance (dynes.sec.cm5)

1 47 DIL CM 32 19 135 95 285 2 52 DIL CM 28 17 118 93 235 3 14 DIL CM 33 20 110 96 197 4 18 DIL CM 30 17 i25 100 225 5 8 SECASD 48 28 85 70 318 6 7 PULMEMB 75 45 90 75 598 7 32 VSD 110 75 105 85 1,056 8 28 VSD 98 67 108 86 978 9 36 PRIM PHT t07 78 112 86 1,264 10 58 MIT ST 105 72 120 90 715

PAP - pulmonary arterial pressure, SAP - systemic arterial pressure, DIL CM - dilated cardiomyopathy,SEC ASD - secundum atrial septal defect, PULM EMB - pulmonary embolic disease, VSD - ventricular septal defect, PRIM PHT - primary pulmonary hypertension, MIT ST- mitral stenosis. 181

Fig. I. Close up photograph of ultrasound catheter tip. The transducer is housed in a sterile plastic sheath with an echolucent dome at the end. Catheter diameter =2 mm. vascular resistances are given in Table 1. Successful intravascular ultrasound images were obtained in 9 out of the 10 subjects; in the patient with mitral stenosis, the ultrasound catheter could not be ade- quately positioned in the pulmonary artery due to marked dilatation of the right heart chambers. In the 4 patients with normal pulmonary artery pressures, a thin vessel wall with no definition of separate layers was seen (Fig. 3). Of the five patients Fig. 3. Real-time cross-sectionalultrasound image from a patient with PHT who were successfully studied, one pa- with normal pulmonary artery pressure. The central circle (large tient (case 5) with mild PHT due to atrial septal de- arrow) represents the ultrasound catheter sheath (approx 2ram fect, had ultrasound appearances similar to those in diameter). The pulmonary arterial wall appears as a single with normal pulmonary artery pressures. In the echogenic ring with no differentiation of separate layers (small arrow). three subjects with systemic level pulmonary artery pressures there was thickening of the intimal layer and the appearance of a three layered arterial wall pulmonary embolic disease there was generalised (Fig. 4). In addition areas consistent with intimal thickening of the pulmonary arterial walls and ar- proliferation were seen in the more distal segments eas consistent with mural thrombus were observed of the vessels studied (Fig. 5). In the patient with (Fig. 6) at sites where there was luminal narrowing on the pulmonary angiogram. No complications of the procedure were encoun- tered and all IVUS examinations were completed within 15 minutes.

Discussion

The pulmonary arteries are thinner than their systemic counterparts and in normal subjects the lobar and segmental arteries (diameter more than l-2mm) have walls comprised of regular, parallel elastic laminae separated by occasional smooth muscle cells and a small amount of collagen. Vessels around 1-2ram diameter have a medial layer of cir- Fig. 2. Radiograph taken during IVUS imagingof the pulmonary cularly orientated smooth muscle between internal arteries showing the catheter as it is being advanced into the pe- and external elastic laminae. Below 0.5 mm, the pul- riphery of the left upper lobe. 182

Fig. 5. Ultrasound image from the same patients as Fig. 2 ob- Fig. 4. Cross-sectional ultrasound image from a patient with sys- tained from a more distal segment of artery showing an area (ar- temic-level pulmonary hypertension due to ventricular septal rowed) consistent with intimat proliferation. defect. There is intimal thickening (large arrow) and appearance of a three layered vessel wall (small arrow). monary arterioles lose the muscular media and their walls are composed of a single elastic lamina. The ultrasound catheter accesses pulmonary arteries 2mm diameter or greater and therefore in normal subjects it is to be expected that only a single layer is seen, as has been described previously. Pulmonary hypertension may result from one of many congenital or aquired disorders, including in- tra and extracardiac shunt lesions, primary pulmonary hypertension, chronic lung disease, thromboembolism and pulmonary venous hypertension secondary to left heart disorders such as mitral stenosis and dilated cardiomyopathy. Initial changes in the pulmonary arterial wall due to PHT consist of medial hypertrophy in the small muscular arteries and extension of the muscular layer into the arterioles which then resemble systemic arterioles. This is followed by cellular and then fibrotic intimal pro- Fig. 6. Cross-sectional ultrasound image from a patient with pul- liferation which leads to organic occlusion of the monary hypertension due to pulmonary embolic disease. There pulmonary arterioles. Subsequent to this there is is generalised vessel wall thickening (large arrow) and an area dilatation of the small pulmonary arteries due to consistent with mural thrombus (small arrow). 183 muscular incompetence. These changes have im- human pulmonary arteries [4] and in patients with portant clinical and prognostic implications [5]. For pulmonary thromboembolic disease [11]. instance, surgical treatment for shunt lesions such Our study confirms that intravascular ultrasound as ventricular septal defect is inadvisable in the face is both safe and feasible in patients with pulmonary of advanced pulmonary vascular disease and when hypertension. We found ultrasonic evidence of cardiac transplantation is being considered for sub- some of the morphological changes associated with jects with severe left ventricular dysfunction, the pulmonary vascular disease in the patients with se- presence irreversible of pulmonary vascular disease vere PHT and in particular of intimal thickening is usually regarded as a contraindication [6] and and proliferation. The appearance of a three lay- would indicate the need for combined heart and ered vessel wall may be due to dilatation of the lung transplantation. It is therefore important in small pulmonary arteries and therefore represent some patients with PHT to establish the severity distinction of intima, muscular media and adventi- and possible reversibility of pulmonary vascular tia or it may be due to some disruption of the nor- changes so that they receive the most appropriate mally elastic pulmonary arterial wall. Pulmonary treatment. angiography was performed in 2 of our patients, in Currently the diagnosis of pulmonary vascular one case to confirm the diagnosis of pulmonary disease and its potential reversibility is based on thromboembolism and in the other (a patient with haemodynamic measurements of pulmonary artery primary pulmonary hypertension) to exclude pressure and resistance and examination of their re- thromboembolism as a cause for her PHT. IVUS sponse to administered oxygen and vasodilator imaged mural thombus at sites of laminal narrow- drugs. Some idea of the extent of pulmonary arte- ing on angiography in the first patient and in addi- rial narrowing can be obtained from pulmonary an- tion appeared to show diffuse vessel wall thickening giography which is also indicated if pulmonary suggesting changes consequent upon the pulmona- thromboembolism is suspected. The morphological ry hypertension. In the other case the pulmonary changes in the pulmonary arterial wall which signify angiogram was typical of primary pulmonary hy- irreversible pulmonary vascular disease can, how- pertension and the ultrasound appearances de- ever only be diagnosed for certain by open lung scribed above were found in the distal vessels. biopsy. Until now this has been the only method of Whilst our study was confined to assessing struc- deciding for certain which patients with shunt le- tural changes in the pulmonary artery wall, this new sions and pulmonary hypertension should undergo imaging technique provides an opportunity to as- corrective surgery and which should be palliated sess the pulsatility and vasoreactMty of the pulmo- [7]. Since it is these morphological changes which nary vessels. Loss of normal vasoreactive responses appear to determine reversibility and hence the have been described in the pulmonary arteries of clinical consequences of pulmonary vascular dis- patients with congestive heart failure using IVUS ease it would be advantagous to be able to obtain [12]. Response of the pulmonary arteries to vasodi- such structural information in vivo, at the time of lators such as nitrates, calcium antagonists, angio- cardiac catheterization. tensin converting enzyme inhibitors and prostacy- Catheter based ultrasound was used in animals as clin could be assessed both accutely and at follow- early as 1960 [8], but it has been over the last decade up in patients with advanced pulmonary hyperten- that the major developments in this imaging tech- sion who may be showing some clinical benefit to nique have taken place. Extensive work in human such therapy. arteries both in vitro and in vivo has shown that One of the drawbacks of the current imaging sys- IVUS accurately delineates systemic arterial wall tem is that using catheters that are 2ram in dia- morphology [9, 10]. Recently reports have con- meter, the vessels most severely involved in pulmo- firmed the feasibility of IVUS, using a 20MHz nary vascular disease are too small to be accessed by transducer, in the evaluation of normal animal and the transducer. Also there is limited information obtained about normal pulmonary arteries because 184 of the relatively thin vessel wall whose individual 3. Isner JM, Losordo DW, Rosenfield K, Ramaswamy K, Kelty S, Pastmore JO, Kosowsky BD. Catheter-based intravascu- layers are not differentiated by ultrasound generat- lar ultrasound discriminates bicuspid from tricuspid valves ed at a frequency of 20MHz. in adults with calcific aortic stenosis. JACC 1990; 15: 1310. 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