1

Case history

A 57-year-old female smoker with a longstanding history of hypertension and diabetes presented to hospital with sudden onset of severe breathlessness in the absence of chest pain. Examination revealed sinus tachycardia, hypertension (blood pressure 200/120) and pulmonary oedema. Routine blood investigations and 12-h troponin measurements were normal, and a diagnosis of acute decompensated heart failure secondary to hypertensive crisis was made. She was treated with diuretics and beta-blockers and made a good recovery. Transthoracic echocardiography demonstrated left ventricular hypertrophy with preserved left ventricular systolic function and Grade 2 diastolic dysfunction. Renal ultrasound confirmed structurally normal kidneys with no evidence of renal artery stenosis. The patient was able to exercise to Stage 3 of a standard Bruce protocol exercise test without symptoms or electrocardiographic changes and subsequent coronary angiography demonstrated a 50% tubular stenosis of the proximal left anterior descending (LAD) artery and 60% stenoses of the mid LAD and origin of the second diagonal (D2) ( Fig. 1 ). Consequently, moderate non-flow-limiting coronary disease was diagnosed, and the patient was discharged with appropriate medical therapy.

Proximal and mid LAD stenoses (identified by arrows).

Unfortunately, the patient re-presented on three subsequent occasions with further episodes of acute pulmonary oedema. The haemodynamic significance of the LAD disease was therefore reassessed, with additional measurements of fractional flow reserve (FFR). This revealed an FFR of 0.71 distal to the mid LAD bifurcation. The D2 and LAD/D2 bifurcation was therefore stented resulting in a post-stent FFR of 0.85 with a pressure “jump” of 0.08 over the proximal vessel on pull-back ( Fig. 2 ). This led to an additional stent being deployed at the site of the proximal LAD stenosis with complete restoration of flow and perfusion in the distal LAD and a post-stent FFR of 0.9 in the distal LAD. Following discharge the patient has remained well and over 18 months, there have been no further episodes of acute pulmonary oedema.

Angiographic result following deployment of stents to the mid LAD and LAD/D2 bifurcation. FFR measurements in the proximal and distal vessels are displayed.

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Discussion

Acute decompensated heart failure is a clinical syndrome characterised by dyspnoea associated with elevated left ventricular filling pressure. This commonly occurs on a background of left ventricular (LV) systolic and/or diastolic dysfunction and is often precipitated by an additional insult i.e. myocardial ischaemia, arrhythmia, or valvular dysfunction. There are also a variety of conditions which can cause acute cardiogenic pulmonary oedema in the absence of heart disease including primary fluid overload, severe hypertension, renal artery stenosis and renal failure.

This case highlights the potential underestimation of angiographically moderate coronary stenoses to be haemodynamically significant, resulting in ischaemic left ventricular failure in the presence of preserved left ventricular function. This is particularly pertinent and relevant in the presence of ventricular hypertrophy as was present here, and should therefore prompt more detailed physiologic assessment of these intermediate severity coronary lesions.

In this patient, the presentations with acute decompensated heart failure are likely to have been precipitated by episodes of painless myocardial ischaemia without infarction, contributed to by the reduced microvascular density of the hypertrophied myocardium. We speculate that sudden reductions in flow through the culprit LAD vessel, or periods of increased myocardial oxygen demand (for example, episodes of acute hypertension in our patient) produced anterior wall ischaemia and transient left ventricular dysfunction. Consequently, LV end-diastolic pressure increased, resulting in sudden onset pulmonary oedema.

The exclusion of all other major causes of acute pulmonary oedema, and the finding of moderate LAD disease on the background of mild LV hypertrophy with preserved ejection fraction appropriately led to further investigation of the angiographic abnormalities, where ultimately complex percutaneous coronary intervention (PCI) was guided by coronary pressure measurements and estimation of FFR.

Defined as the ratio of maximum blood flow in the presence of a coronary stenosis to normal maximum flow, FFR gives a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary and central venous pressure during pharmacologic vasodilation. This method first described by Gould et al. in 1982 , has been validated by animal and human studies. It provides a robust index of coronary stenosis severity independent of changes in heart rate, blood pressure and contractility, also accounting for the contribution of collateral flow to total myocardial perfusion. It is generally accepted that an FFR <0.75 is representative of significant ischemia in the myocardial region subtended by the stenotic coronary artery .

Angiography is often inaccurate, and limited in its ability to distinguish the severity of intermediate coronary artery stenoses. Up to 50% of patients with angiographic intermediate stenoses of 40–70%, but no documented evidence of inducible ischaemia, prove to have functionally significant disease when subjected to FFR assessment . In a population of patients with multivessel disease, more than 60% of lesions have been shown to be of functional significance .

The assessment of the functional significance of coronary disease in this setting is of crucial importance as it identifies those patients at high risk and distinguishes them from those who derive no benefit from angioplasty.

Following angiographic optimum stent deployment and restoration of flow, there should be complete resolution of the hyperaemic pressure gradient, and so, in this context, FFR measurement can yield additional important prognostic information. Studies have not only shown FFR to have a high specificity compared with intravascular ultrasound for detecting adequate stent implantation but have also shown that FFR after stenting is a good predictor of cardiovascular outcome, demonstrating a strong inverse correlation with event rate during follow-up .

In our patient, the FFR in the distal LAD following deployment of the mid LAD and D2 stents was 0.85, and pullback of the pressure wire revealed a jump to 0.93 as the wire crossed the more proximal LAD lesion which prompted the deployment of a third stent at this site resulting in a FFR-guided PCI strategy finally leaving a FFR reading of 0.90 in the distal LAD.

In summary, this case demonstrates the importance of excluding an ischaemic precipitant in cases of unheralded acute pulmonary oedema and preserved left ventricular function. The pressure wire in this setting provides essential additional diagnostic information in the context of “intermediate coronary artery lesions,” particularly when other noninvasive measures of ischaemia are equivocal.