The Pickering Syndrome – A pebble in the mosaic of the cardiorenal syndrome

In the present issue of Blood Pressure, Anna Pelta and colleagues (1) documented in the Copenhagen county cohort that flash pulmonary edema (FPE) was more common in patients with bilateral renal artery stenosis (RAS) than with unilateral disease. The clinical entity of FPE and bilateral RAS is now known as Pickering Syndrome (2). In a Lancet article in 1988, Thomas Pickering and colleagues were the first to bring this clinical observation to our attention (3). Most patients with FPE have bilateral RAS although in both the present and Pickering's series, FPE was also seen in a few patients with unilateral RAS. Of interest, only one patient of eight who developed FPE had severe left ventricular (LV) systolic dysfunction. This clearly attests to the fact that in patients with Pickering Syndrome, FPE can occur with normal or only mildly impaired LV systolic function. However, this does not hold true for diastolic function; patients with Pickering Syndrome most commonly present with severely impaired LV filling and LV hypertrophy. This, together with defective natriuresis secondary to bilateral RAS, is the main pathogenetic mechanism leading to FPE.

There is nothing magic with FPE – it is just a useful clinical term to describe a particularly dramatic form of acute decompensated heart failure. The fact that flooding of the alveolar space can occur within minutes resulting in an acute life-threatening emergency is what distinguishes FPE from other forms of decompensated heart failure (4). Regardless of its etiology, an acute increase of the LV end-diastolic pressure is the common denominator for the development of FPE. Of note, FPE is also seen in patients with acute myocardial infarction and acute severe mitral regurgitation. However, the presence of recurrent FPE, lack of typical angina, increased blood pressure and elevated creatinine should raise the suspicion of bilateral RAS and hence Pickering Syndrome as a possible etiology for FPE.

In the series described by Pickering, FPE occurred on average 2.3 times before the diagnosis of RAS was made and in the present study, three-quarters of all patients had more than one episode of FPE. This would indicate that Pickering Syndrome, not uncommonly, presents a diagnostic conundrum. Classically, these patients have some degree of renal failure and present with sudden onset of severe unprovoked dyspnea (“flash” pulmonary edema). The presence of low-grade coronary artery disease may result in misinterpretation of FPE being caused by coronary ischemia. The frequent nocturnal appearance of FPE may be related to reverse nocturnal dipping, which has been well documented in patients with RAS. Acute management of FPE is aimed at maintaining adequate oxygenation, diuresis, decrease of pulmonary capillary pressure and treatment of underlying cause. However, aggressive treatment of FPE in patients with bilateral RAS usually will cause a further decrease of glomerular filtration rate and hyperkalemia may ensue.

Renal revascularization is the treatment of choice once the patient is stable and FPE has been resolved. The AHA/ACC guidelines endorse revascularization as a class 1 recommendation for patients with hemodynamic significant RAS and recurrent unexplained congestive heart failure or pulmonary edema (5). In our analysis, 92% of all patients had no further FPE after revascularization (2). Pelta et al. observed two instances of FPE after angioplasty – one of which was caused by restenosis and the other seemed to have been triggered by atrial fibrillation. Patients with recurrent FPE after renal artery stenting should have repeat Doppler ultrasound of the kidneys to rule out recurrent RAS.

Pickering Syndrome is part of the cardiorenal syndrome, a pathophysiological condition in which impairment of cardiac and renal function mutually accelerate each other. A variety of pathogenetic mechanisms associated with the cardiorenal syndrome have recently been identified (6). However, in contrast to Pickering Syndrome, which is a unique pebble in this mosaic and has a well-defined pathogenetic mechanism, many aspects of the cardiorenal syndrome still remain somewhat nebulous. Pickering Syndrome is likely to serve as an illuminating teaching model, shedding light on at least one straightforward aspect of the complex interaction between the kidney and heart.

Thomas Pickering (picture) dedicated his career in cardiovascular medicine to research, teaching and patient care. His original report to the association of FPE with bilateral RAS clearly bears witness to outstanding clinical expertise. Pickering Syndrome must be considered a quintessential pathophysiological model attesting to pre-eminence in research and clinical skills of its first observer.