|CASE SERIES IN PVD
|Year : 2009 | Volume
| Issue : 3 | Page : 186-190
Case studies of congenital heart disease with pulmonary hypertension: Atrial septal defect
Srinivas Laksmivenkateshiah, Raman Krishna Kumar
Department of Pediatric Cardiology, Amrita Institute of Medical Sciences, Amrita Lane, AIMS Ponnekkara PO, Kochi-682 041, India
|Date of Web Publication||27-Jul-2009|
Raman Krishna Kumar
Department of Pediatric Cardiology, Amrita Institute of Medical Sciences, Amrita Lane, AIMS Ponekkara PO, Kochi-682 041
| Abstract|| |
Pulmonary arterial hypertension (PAH) develops in 10-16% of patients with atrial septal defect (ASD). The determinants of occurrence of PAH in ASD are not clear. There does not appear to be a relationship between duration of exposure to increased pulmonary blood flow and the development of PAH. Once PAH develops, it is challenging to determine operability and predict outcomes after repair in borderline situations. Two illustrative cases of ASD and PAH; an infant and an adult who were evaluated for operability and factors that were considered in decision-making are discussed. Their subsequent follow-up is also presented to illustrate their modified history following closure of the ASD.
|How to cite this article:|
Laksmivenkateshiah S, Kumar RK. Case studies of congenital heart disease with pulmonary hypertension: Atrial septal defect. PVRI Review 2009;1:186-90
|How to cite this URL:|
Laksmivenkateshiah S, Kumar RK. Case studies of congenital heart disease with pulmonary hypertension: Atrial septal defect. PVRI Review [serial online] 2009 [cited 2013 May 25];1:186-90. Available from: http://www.pvrireview.org/text.asp?2009/1/3/186/54761
| Case 1|| |
A 25-year-old woman was detected to have atrial septal defect (ASD) when she was evaluated for a respiratory tract infection. She was asymptomatic at the time of detection of heart disease. Systemic examination was remarkable for a normal first heart sound, wide fixed split second sound with pulmonary component equal to that of aortic, an ejection systolic murmur at the left second intercostal space. No mid-diastolic flow murmur was audible. Oxygen saturation was 94% by pulse oximetry. Chest roentgenogram [Figure 1] showed cardiothoracic ratio of 50%, dilated main and branch pulmonary arteries with no features of increased pulmonary blood flow. Electrocardiogram showed right axis deviation and incomplete right bundle branch block pattern [Figure 2]. The ASD measured 25 mm on echocardiography with right atrial (RA) and right ventricular (RV) enlargement. The defect appeared to shunt from left-to-right. Right ventricular systolic pressure (RVSP) was 68 mmHg as estimated by Tricuspid regurgitation (TR) jet velocity. Partial pressure of oxygen (PaO 2 ) was 84.7 mmHg before and 56.2 mmHg after a symptom-limited treadmill exercise.
|Figure 1: Case#1: Chest roentgenogram in posterior–anterior view, which shows a cardiothoracic ratio of 50% with dilated main and branch pulmonary arteries and no increase in pulmonary vascularity|
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|Figure 2: Case#1: Twelve channel electrocardiogram which is unremarkable except for right axis deviation of QRS vector (105º)|
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The cardiac catheterization findings are summarized in [Table 1] and [Table 2]. Pulmonary to systemic blood flow ratio (Qp/Qs) was 2.9 : 1 and pulmonary vascular resistance index (PVRI) was 7.47 WU·m 2 . On administration of a mixture of 5 L/min oxygen and 40 ppm nitric oxide, Qp/Qs increased to 3.81 and PVRI dropped to 6.5 WU·m 2 . On balloon occlusion of ASD for 10 min, mean PA pressure decreased by 14 mmHg to 1/3 rd systemic pressure without a significant change in the mean systemic arterial pressure.
The defect was closed with a 28 mm ASD device (Lifetech Scientific Ltd., Shenzen, China). A 6 mm fenestration was created in the device before deployment. She was discharged on oral phosphodiesterase 5 inhibitors. It has been a year since the procedure and on follow-up she continues to be asymptomatic. The fenestration in the ASD device was found to be closed and she has mild pulmonary regurgitation with peak gradient of 22 mmHg. The RV systolic pressure is sub-systemic as determined by end systolic septal position.
| Discussion Case #1|| |
Patients with ASDs and PAH form a distinct subgroup and there remains much debate regarding the nature and underlying etiopathogenesis of pulmonary hypertension in this context.  Pulmonary hypertension in pre-tricuspid shunts (such as ASD, partial anomalous pulmonary venous communication) does not result from direct transmission of pressure from systemic to pulmonary circulation. This is unlike in post-tricuspid shunts (such as ventricular septal defect, patent ductus arteriosus or aorto-pulmonary window), where pulmonary circulation is exposed to the systemic pressure head. Here, severe PAH may result from increased pulmonary blood flow alone.
Traditionally, comprehensive evaluation of patients with left-to-right shunts and PAH includes clinical assessment, chest roentgenogram, echocardiogram and cardiac catheterization for quantification of left-to-right shunts and PVRI.  In most situations, decisions on operability are straightforward as most modalities are internally consistent. Occasionally, however, there are internal inconsistencies. Some of these investigations may suggest a large resting shunts and operability, while others suggest significant elevation in PVR. Decision-making regarding operability is quite challenging in these circumstances.
Case #1 has been presented to illustrate the limitations of available clinical and investigational tools in determination of operability. We will discuss each of the modalities used in this patient.
A loud pulmonary component of the second heart (P2) sound and fixed splitting are invariably seen in most patients with ASD irrespective of the pulmonary artery pressures. The diastolic flow murmur may diminish as the shunt ratio declines from progressive elevation of pulmonary vascular resistance. However, this physical sign is limited by poor sensitivity. Many patients with large shunt ratios may not have a flow murmur. This physical sign is also quite subtle and its utility may have suffered from declining auscultation skills of modern day cardiologists. Role of ejection systolic murmur is limited.
The X-ray signs of in increased pulmonary blood flow have not been validated with shunt ratios and late outcomes after closure of the defect. The chest X-ray in patients with ASD can show features of increased pulmonary blood flow even after elevation of PVR occurs. This is because the distal vessels may remain dilated. This is unlike in patients with post-tricuspid shunts, where the pulmonary vasculature is subjected to elevated flows from birth and may not therefore develop normally. In spite of these limitations, many cardiologists in India continue to respect X-ray findings and incorporate the information in decision-making. In this case, the chest X-ray [Figure 2] does not correlate with catheterization data.
The ECG may show evidence of unequivocal RVH once elevated PVR sets in. However, both the sensitivity and specificity of RVH as a predictor of PAH is limited.
Echocardiography allows semi-quantitative assessment of shunt ratio and an approximate estimate of pulmonary arterial systolic pressures. The flow direction across the defect can also be visualized. Information from echocardiography alone does not allow decision-making in borderline cases.
Arterial blood gas estimation and the effect of exercise
Exercise physiology induced cardiopulmonary compensations provides an additional tool to evaluate hemodynamics of pulmonary and systemic blood flow in patients with shunt lesions. Exercise has been shown to increase Qs with corresponding increase in Qp without alteration in PVR in patients with moderate- sized ventricular septal defects and normal PA pressure.  In patients with pulmonary hypertension and elevated PVRI, Qp is unlikely to increase to the extent required by the exercise, while Qs is likely to increase significantly as systemic vascular resistance decreases. Exercise-induced right-to-left shunt has been demonstrated in patients with pulmonary hypertension and patent foramen ovale.  In this patient, there was a significant decline in PaO 2 by 21 mmHg following exercise. This modality is being systematically investigated at our institution. Preliminary results suggest that a >10 mmHg decline in PaO 2 predicts a basal PVRI > 7 wood units with high sensitivity and specificity.
Hemodynamic studies to calculate flows and resistances in the pulmonary and systemic circulations should be done meticulously and efficiently such that saturation and pressure measurements are obtained under more or less identical physiological conditions. There are several sources for error during cardiac catheterization which needs to be considered.  They include assumption of oxygen consumption and sampling errors. Erroneous data compounds the problems of decision-making in an already borderline situation. In this case, the baseline data was truly a borderline. The numbers were all calculated after assuming oxygen consumption. The resting PVRI of >7 units suggested that PA pressures may not decline after closure of the defect. However, a resting Qp/Qs ratio of 2.9 was encouraging and suggested the presence of a significantly increased pulmonary blood flow. Calculation of this parameter is independent of oxygen consumption.
Testing pulmonary vasoreactivity
Commonly used agents to test pulmonary vasoreactivity are oxygen, nitric oxide, , intravenous prostacycline and very recently milrinone.  Though these agents intuitively appear to test the 'reversible' component, there are several caveats in using them routinely. Quantification of shunts and PVRI in cath lab is based on Fick's principle. There are several sources of error in such estimations and most important of which is the assumption of oxygen consumption. , In our patient, the PVRI marginally declined to 6.5 units.
Testing the effect of balloon occlusion of the defect
Role of balloon occlusion of left-to-right shunt and resultant decline in PA pressure is a useful indicator of hyperdynamic PAH in a patient with patent ductus arteriosus. ,, Balloon occlusion of ASD to test reversibility is reported in a few case series.  Whether an acute fall in the PA pressure will translate into favorable long-term outcome is unknown. In our case, the decline in PA pressure after balloon occlusion was impressive and encouraged us to close the defect.
| Case # 2|| |
A five-month-old baby girl presented with complaints of interrupted feeding, chest retractions and failure to thrive since she was 3 months of age. She weighed 4.7 kg and was tachypneic. She had no dysmorphic features and cardiovascular system examination revealed cardiac enlargement, wide and fixed split second sound, ejection systolic murmur at left second space and a mid-diastolic murmur at lower left sternal border. Oxygen saturation was 97% measured using a pulse oxymeter. Cardiothoracic ratio was 65% with normal pulmonary vascularity on chest roentgenogram [Figure 3]. Electrocardiogram revealed right axis deviation of QRS vector with significant right ventricular hypertrophy [Figure 4]. Echocardiogram was remarkable for a 12 mm large ASD, dilatation of RA/RV and normal pulmonary venous drainage. Estimated RVSP by TR jet was 54 mmHg + RA pressure. Cardiac catheterization data [Table 3] was consistent with a large left-to-right shunt with Qp/Qs of 3·2:1 and moderate PAH with a mean pulmonary artery pressure of 32 mmHg (half systemic). PVRI was 2.3 WU.m 2 . On administration of 100% oxygen, Qp/Qs increased to >4:1 and PVRI dropped to 0.29 WU·m 2 [Table 4]. No other causes of PAH was evident. The defect was closed surgically.
|Figure 3: Case#2: Chest roentgenogram in posterior–anterior view, which shows a cardiothoracic ratio of 65% with normal pulmonary vascularity|
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|Figure 4: Case#2: Twelve channel electrocardiogram, which shows right axis deviation of QRS vector (120º) and signifi cant right ventricular hypertrophy|
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She persisted to have mean pulmonary artery pressure 2/3 rd systemic in the post-operative period. She was discharged on oral diuretics and oral phosphodiesterase type 5 inhibitors. She was followed up on a regular basis. Serial echocardiograms showed persistence of significant PAH. At present she is 7 years old. She has symptoms of dyspnea on effort (Class II) and has limited her activity. Her weight and height are appropriate for age. On echocardiography, she continues to have significant RA and RV dilatation [Figure 5], RV dysfunction, PAH with moderate TR and estimated RV systolic pressure of 84 mmHg.
|Figure 5: Case#2: Apical four chamber echocardiogram image 7 years after the closure of ASD. Right ventricle was dysfunctional and there was signifi cant right atrial and ventricular dilatation. Severe hypertensive tricuspid regurgitation is also seen.|
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| Discussion (Case #2)|| |
This case is being presented as an example of persistence of pulmonary hypertension following ASD closure. At initial assessment there was increased pulmonary blood flow and the pulmonary vascular resistance was in the 'operable' range. The persistence of PAH seven years after defect closure was not anticipated. This clearly illustrates the limitations in our understanding of the factors that determine the occurrence of pulmonary hypertension in selected patients with ASD.
Pulmonary hypertension in patients with ASD is thought to be an acquired phenomenon and is believed to set in after 2 nd or 3 rd decade of life. In a study by Cherian et al., amongst 93 patients possessing ASD with PVRI of >5 WU·m 2 , 12% were younger than 10 years.  Though uncommon, onset of heart failure symptoms in infants with ASD is well-documented. ,,, Many of such patients also have had PAH. Based on case reports, many such infants have increased incidence of dysmorphism. ,
Infants presenting with ASD and PAH are usually symptomatic with heart failure, and therefore warrant closure of the defect. They are known to have high Qp/Qs and moderately elevated PVRI. , Many such patients have favorable response to pulmonary vasodilator testing.  Surgical or device closure in such patients is reported to be safe. , Pulmonary hypertensive crisis in the immediate post-operative period has been reported.  Though pulmonary artery pressure regress in most of the patients, a small number of them continue to have PAH. , The reason for persistent PAH is unclear, but could be because of associated chromosomal anomalies  or associated respiratory pathology (neither of which were present in our patient).
Close follow-up of all patients who have pulmonary hypertension in association with ASD is perhaps mandatory. There are a very few specific treatment options for patients who persist to have PAH even after the closure of ASD. Several pulmonary vasodilators are available for long-term use., phosphodiesterase-5 inhibitors, endothelin receptor blockers are known to improve quality-of-life and actually decrease PA pressure over long-term use in many patients. However, apart from sildenafil, most treatment options for pulmonary hypertension are either unavailable or extremely expensive in most of the developing world. As a result, the treatment options for this girl are very much limited at this stage. Clearly, sildenafil alone appears inadequate and addition of bosentan and/or prostacycline analog is warranted. Other possibilities include creation of a fenestration in the atrial septum (atrial septal stenting or insertion of a fenestrated device) and of heart-lung or lung transplantation as a final option.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]