Renal Unit, Guy's and St Thomas' Hospital, London, UK
Introduction
The reason for the title is that since Pickering et al. [1] first described this condition in 1988, there have been a number of papers confirming this as a distinct clinical entity [26]. However, it is unclear as to how often it is recognized. This is probably because it falls into a watershed between cardiology and nephrology. These patients have pulmonary oedema but neither severely impaired left ventricular function nor severely impaired renal function.
Case description
The following case description illustrates the problem. A 56-year-old female smoker with a 10 year history of difficult to control hypertension presented to hospital with acute shortness of breath and chest tightness. On the following day her breathlessness worsened with further chest discomfort. There were some anterior lead electrocardiogram alterations suggestive of an anterior myocardial infarction and she was treated with thrombolysis. There was no change in the cardiac enzymes nor did her electrocardiogram change. She was noted to have impaired renal function with a plasma creatinine of 444 µmol/l. She was treated with diuretics and nitrates with improvement in her shortness of breath and her plasma creatinine fell to 270 µmol/l. She then underwent coronary angiography which was entirely normal but a renal angiogram was performed which is shown in Figure 1. The aorta shows no evidence of atheromatous disease and the angiogram was thought to be compatible with fibromuscular dysplasia in keeping with her early onset hypertension. She underwent left renal angioplasty and right renal artery stenting. Her plasma creatinine has fallen to below 100 µmol/l since the angioplasty and she has had no further attack of shortness of breath 3 years later. She has been reviewed by a cardiologist who has found no evidence of ischaemic heart disease in any of the preceding investigations.
|
Discussion
This case illustrates the difficulty in diagnosing an important and treatable acute pulmonary oedema. The association of proven cardiac disease and pulmonary oedema even requiring ventilation can lead to an incorrect diagnosis as in this case. In the first series the mean number of attacks of pulmonary oedema was 2.3 before the diagnosis was made [1]. In the Weatherford et al. series it was 2.5 prior to intervention [4]. The case of Kwan et al. had had 3 attacks prior to investigation [12]. The patient reported by Farmer et al. [5] had been investigated for dyspnoea prior to diagnosis but had been discharged by a cardiology clinic as she had a good left ventricular dysfunction. She subsequently was admitted three times with flash pulmonary oedema, being ventilated on two occasions. Diamond [2] reports one patient who had flash pulmonary oedema frequently after coronary artery bypass grafting and on one occasion had a respiratory arrest before the diagnosis was made! All these reports show how late the diagnosis is made because an echocardiogram showing good left ventricular function had led to a false sense of security in the physician or more usually the cardiologist.
The original description occurred only in 1988 but has now become recognized as a distinct clinical entity. The reason for this is that all the individuals involved in the original description [1] had significant coronary artery disease. In fact, in five of the original series of 11 a rise in plasma creatinine on an ACEI had already occurred before the diagnosis of renovascular disease was made. These patients did have significant heart disease. However, it is only because the specific symptom of pulmonary oedema was improved by angioplasty or renal artery bypass graft that the relationship between the renal artery narrowing and the pathophysiological condition was established. In a second series in the original paper the correlation was found with bilateral or unilateral disease with a sole functioning kidney. A further review by the same group [6] has shown that pulmonary oedema occurred in 41% of patients with bilateral and 12% of patients with unilateral disease. After stent placement, 22 out of 27 patients with bilateral disease improved whereas only one of the three patients with unilateral disease improved. Thus the observation in the original paper that the syndrome occurs when all the functioning renal mass is supplied by a stenotic artery is strongly supported. Others have suggested a stronger correlation with renal artery occlusion combined with stenosis [3].
Following the original description, Missouris et al. [7] described two cases where the presentation was severe heart failure. In the first case renovascular disease was only suspected with an increase in plasma creatinine with an ACEI. In each case the proof of the diagnosis was the dramatic naturesis and improvement in symptoms after the relief of renal artery stenosis in single functioning kidneys. These cases are, however, different from the original description as their symptoms were chronic. In many ways this may be easy to understand and explain by the mechanisms suggested by Pickering et al. [1] of the blunting of the effect of a pressure naturesis due to renal artery narrowing and decreased perfusion pressure to the kidney and tubule.
The importance of renovascular disease in chronic congestive cardiac failure is unclear. There have been no subsequent larger series reporting dramatic improvement in stable congestive failure. However, MacDowall et al. [8] have shown that in a general medical clinic there is an incidence of over 30% of renovascular disease in patients presenting with cardiac failure with a plasma creatinine of less than 300 µmol/l. The only way to prove a causal relationship in such a situation is a positive response to intervention and the Missouris et al. study represents the only series at present of patients in heart failure [7]. Khosla et al. [9] do however suggest a possible improvement in New York Heart Association classification of patients following intervention although the same was also true in patients who had not undergone intervention!
In fact, the original report does not include the features we would now recognize for this condition which are the acute and unprovoked nature of the pulmonary oedema [1]. The abrupt nature of the condition gives it its usual name: flash pulmonary oedema. Planken and Ritveld [10] report two cases where the precipitating factors were swimming and central venous catheterization. Harker et al. [11] reported a case where a patient with poor left ventricular function was precipitated into acute pulmonary oedema by angioplasty to one renal artery in a patient with bilateral renal artery stenosis. Interestingly, Kwan et al. [12] report a case of Pulsus Alternans in a patient with bilateral renovascular disease which was cured by angioplasty. Pulsus Alternans is usually associated with impaired left ventricular systolic dysfunction but occurred in this individual with a normal ejection fraction. The patient in this report had been admitted three times in pulmonary oedema in the 9 months prior to investigation. The report indicates that these changes were present when the patient was relatively stable during investigation. This suggests that even without the full blown episode of flash pulmonary oedema subtle abnormalities of left ventricular dysfunction can be found. Weatherford et al. [4] in their series of five patients could not document an abnormality of systolic cardiac function prior to intervention. One common clinical feature not commented in all the papers is that many patients experience their flash pulmonary oedema only at night. The frequent history is of a patient going to sleep without dyspnoea but awoken in the night with shortness of breath which may require ventilation. An unproved suggestion might be that these patients have severe renal artery lesions which are non-critical during the day with normal ambulant blood pressure, but with a nocturnal dip in blood pressure the lesion becomes critical provoking severe perturbation of the renin-angiotensin system. As explained above, this is the much more common clinical presentation rather than one of stable congestive failure.
Conclusion
Flash pulmonary oedema is an important diagnosis to make. In many issues in renovascular disease there is no good evidence base for either intervention or non-intervention. However most authorities would recognize flash pulmonary oedema as an absolute indication for intervention. In our experience it rarely occurs during the waking hours and it may present a response to nocturnal hypotension in hypertensive patients who maintain their nocturnal dipping of blood pressure. Whatever the exact physiology it is a rewarding condition to treat and one which we and our cardiological colleagues would be wise to entertain.
Notes
Correspondence and offprint requests to: J. E. Scoble, Renal Unit, Guy's and St Thomas' Hospital, St Thomas Street, London 3E1 9RT, UK.
References