Stent Pain? What Do You Think?

47 year old male. Past history of stents to LAD and Cx in 2005 for stable angina. Treated for hypertension and hyperlipidemia. Recurrent chest pain since the stents were placed, sounds anginal in nature. Between times he is fine, walks 1 mile on flat ground with no problem. Several hospital admissions with troponin negative events, without new ECG changes. Serial angiograms have shown no progression of his coronary artery disease; stents show minor degrees of in-stent stenosis only; not felt to be functionally significant.

Where next with this patient?

Echo during pain showed no regional wall motion abnormalities.

Could this be 'stent pain syndrome'? Small vessel disease?

What to do next?

Is this a scenario you have seen before?

Suggestions welcome in the comments!

Being a doctor on-call is bad for your health!

Another cardiovascular risk factor - 24 hour hospital shifts! A paper published in the November 2009 European Heart Journal (http://eurheartj.oxfordjournals.org/cgi/content/abstract/30/21/2606) examined the effects of a long workday on several markers of cardiovascular stress.

30 healthy physicians (aged 29-45 years) were monitored by 24 ECG, urine collection, blood tests and sleep diaries. This gave a snapshot of the consequences of their work on their cardiovascular, neuroendocrine and inflammatory systems. The novel aspect of the study was its prospective, randomised crossover design. This meant that each subject completed not only a 24 hour ‘on-call’ shift, but also a 24 hour ‘not on-call’ day featuring only 8 hours of work followed by sleeping at home. Doctors were recruited across three specialities - neurology, internal medicine and ENT at Innsbruck University Hospital, Austria.

Being on-call was associated with higher blood levels of tumour necrosis factor, as well as higher urine levels of adrenaline and noradrenaline. Blood pressure values were also greater whilst working. There were more VPB’s noted during ECG monitoring. These effects are likely due to changes in the balance between sympathetic and parasympathetic systems induced by being awake for longer.

Some of this is not new. It’s already known that irregular working hours are associated with an increased incidence of cardiovascular disease including MI, even when corrected for existing risk factors.

What can we conclude? It seems that pulling 24 hour shifts disturbs several body systems and alters your risk factor profile towards cardiovascular disease. Working at night is a necessary evil as patients don’t stop needing treatment at 5pm. But perhaps shorter shifts with longer rest breaks might ultimately give us healthier doctors.

Cardiac CT Gathers Prognostic Momentum

There’s increasing evidence that CT is becoming better at identifying ‘high risk’ features of atherosclerotic plaque in the coronary arteries. In a recent paper by Motoyama and colleagues, over 1000 patients were imaged at baseline - generating a total of 10,000 coronary segments for analysis. These middle-aged subjects (mean age 64) all had CT imaging for known or suspected coronary artery disease. This painstaking effort yielded some worthwhile results. Subjects were followed for an average of 27 months and those with acute coronary syndromes were identified. Two plaque characteristics emerged that were associated with an adverse outcome - the presence of positive outward arterial remodelling (PR) and an area of plaque with low attenuation (LAP). Cut-off values for these two features were based on previous studies that validated cardiac CT against IVUS.

Although the absolute number of events was very small (just 15 in the entire cohort), the presence of PR and LAP increased the hazard ratio for an event to over 22. Of the 1059 subjects imaged, only 45 had both high-risk features in the same plaque; these subjects had a 22% chance of an event during the next 2 years. Compare this to the <0.5% event rate in those with plaques without these two features. Another fascinating conclusion was that those patients harboring plaques with the largest LAP or RP volumes had earlier ACS events. Reassuringly, no patient identified as having zero plaque disease by CT developed subsequent ACS during the follow-up period.

Additionally, there is evidence that ANY degree of coronary atherosclerosis on cardiac CT bestows an adverse prognosis. On the contrary, if cardiac CT reveals no atherosclerosis, the 1 and 3 year event rates are as low as 0.5% and 1.2% respectively (Matsumoto N, et al Circ J. 2007;71(12):1898-1903. Pundziute G, et al JACC 2007;49(1):62-70).

How does this translate into practical approaches to CT, and especially guidelines for the appropriate use of the technology?

It’s clear that with the rapid development of CT hardware, combined with more intuitive plaque characterization algorithms that the use of CT will likely continue to increase. Non-invasive monitoring of plaque volume over time by CT is already possible, published by Burgstahler in 2007, where statin therapy caused a reduction in plaque volume of approaching 25%. We are likely to see increased use being made of this technology by pharmaceutical companies searching for novel surrogate markers of drug efficacy. As ever, the radiation dose is the Achilles heel of the technology, although the CT vendors are tackling this with the current generation of machines.

Chalk and Cheese - Calcification, Perfusion and Prognosis

A thought-provoking paper was published recently in JACC.

Over 1100 largely asymptomatic intermediate Framingham risk patients underwent calcium scoring and perfusion imaging by SPECT. The commonest indication for testing was atypical chest pain. Follow-up was for almost a decade and there were a large number of CV events. The investigators, from Houston, Texas, concluded that calcium scoring was a good predictor of long-term cardiovascular events, with SPECT imaging a better predictor of near-term events.

It's already known that a normal SPECT study confers an annual CV event rate <1%. This finding was confirmed here. But the fascinating part for me was data showing that the 'warranty period' for the reassurance of a normal SPECT study expires after about 3 years if the calcium score is greater than 400. Presumably this is because calcium scoring is a surrogate marker for both 'high risk' non-calcified plaques (at risk of rupture) as well as calcified plaque. SPECT will only be sensitive to coronary plaques once they have become flow-limiting. The authors suggest obtaining a calcium score in subjects with a normal SPECT study, if patients are perceived to be at high risk of future events.

This advice is the opposite of that currently endorsed by the ACCF/ASNC guidelines, which suggest SPECT imaging is useful in patients who have calcium scores>400.

 Do you think this is a useful way forward for patients falling into the intermediate and high risk Framingham categories with a normal SPECT study? Are you worried about the radiation burden of SPECT plus CT? Should we just prescribe lifestyle/lipid management rather than further imaging?

Incidentally...the Perils and Pitfalls of Cardiac CT

I've just finished reading a very insightful paper in JACC, also covered on heartwire (http://www.theheart.org/article/1010849.do).

It describes a single centre Canadian experience of performing cardiac CT in over 950 patients. All images were reported by experienced radiologists and they calculated the number of non-cardiac incidental findings (IFs) that were thrown up on cardiac CT. Moreover, also included were analyses of the extra cost of investigating the IFs, along with extra attributable radiation exposure. The investigators also provided some follow-up data out to an average of 18 months.

Although incidental findings in this middle-aged group were very common (41.5% of all patients), the striking thing is that almost all of them were of no clinical significance (98.8%). The majority of the non-cardiac findings were in the lungs - pulmonary nodules and emphysematous changes led the list. Investigation of findings of indeterminate significance was costly and potentially hazardous to both patients and healthcare providers.

Further reassurance was provided by the follow-up data. There was no difference in mortality between the patients with IFs and those without, including cancer deaths.

As cardiologists, how do you deal with reading the non-cardiac portion of the CT scan?

Should all studies be reported by radiologists? Should all studies be jointly reported by both a cardiologist and a radiologist?

One other option, suggested in the accompanying editorial, is to let the patient decide, after informed consent whether they would like the non-cardiac structures evaluated or not. Is this a cop out, or is this the only way to truly act in the patient's best interests?

The issues are complex and cross into medical ethics and best practice. It it is already known that screen for lung cancer by CT is not effective. Why then should we report on lung nodules just because they are there?

Please let us know your opinion in the comments and also add your vote to the poll.

What's the Risk of Bypass Plus Heparin to the Brain?

Hypothetical case: 50 year old male, previously well on no meds, presents with left parietal lobe intracerebral haemorrhage. Has fever and a murmur - echo shows large AV vegetation with positive blood cultures for diphtheroid organisms. There is free-flowing aortic regurgitation. He has a dense right sided hemiparesis which gradually improves over the next 3 weeks. Serial echo demonstrate an enlarging LV - LViDD 5.1 to 5.4 to 5.9cm over 3 weeks. Overall LV function remains good. Other heart valves normal on TEE.

His fever/CRP respond well to conventional IV antibiotic therapy.

Clearly the patient needs aortic valve replacement. Likely he had an embolic event from his AV that induced haemorrhage in his brain. My question is how long to delay AVR? There is a risk of his LV dilating more, but also the risk of bleeding into his brain when he is placed on bypass and fully heparinised.

Any comments?

Hippocrates and Chest Pain

"Life is short, the art long, opportunity fleeting, experiment treacherous, judgment difficult"

So wrote Hippocrates, father of medicine, some 2400 years ago in his book of Aphorisms. Most of that statement still holds today, except we live about twice as long on average.

Judgement remains difficult, especially when it comes to investigating patients with heart disease. Speakers during a well-attended session today at ESC heard from Dr Bax (Leiden, Netherlands) who explained how he approaches non-invasive imaging in the patient with chest pain. We need to search not only for evidence of atherosclerosis, but also coronary stenoses and their functional consequences. We must always be mindful of Bayesian effects. If the pre-test probability of disease is either very high or very low, then imaging (except coronary angiography) is of little use. I could add prognosis to his list of requirements of an imaging test.

Imaging is going to feel the cold wind of the global financial crisis - according to James Thomas of the Cleveland Clinic, at least in US. The rapid rise in imaging tests over the last 10 years have brought many benefits but at huge costs, both financial and in some cases worrying radiation exposure levels (see NEJM last week).

So we may be forced to rationalise our approach to the 45 year old man with atypical chest pain, positive family history, normal resting ECG and a non-diagnostic exercise test.

What would you do to investigate him? Straight to cath? CT angio? Perfusion imaging? Stress echo? Perhaps the one-stop-shop of cardiac MR?

Sometimes too many options are a bad thing. Although when it comes to Tapas I disagree....

Picking the plaques that go pop

Another exciting day in Barcelona. The highlight for me was a session dedicated to imaging of atherosclerosis, both from within the coronary arteries and non-invasively. My take-home message was that whilst we have many ways of quantifying the extent, structure and functional state of atherosclerosis in the coronary arteries and elsewhere, we are still in desperate need of prospective trials in this area. It is all very well to image atheroma; as clinicians we need to know more - we need to know which patients will suffer CV events in the future. We can choose from risk scores, such as Framingham. We can use circulating biomarkers - CRP, lipids and many others. And finally imaging of atherosclerosis. How to bring them all together?

Thankfully, there are a couple of very interesting trials underway. The first is the High Risk Plaque BioImage study, co-ordinated by BG Medicine in USA. This large, prospective, event-driven study in asymptomatic subjects has already recruited over 5000 patients for imaging (CT, MRI, FDG PET, IMT, calcium score) plus biomarkers. Over the next 3 years, CV events will occur in these patients; as a result we will discover the true 'predictability' of these modalities.

The second trial of huge interest is the PROSPECT study, due to be reported at TCT in San Francisco in late September. This focusses on invasive plaque assessment with coronary angiography, palpography and IVUS-VH and again attempts to predict events on the basis of imaging and circulating biomarkers over a 3 year period.

Let us know in the comments your thoughts on invasive and non-invasive plaque imaging.