Day 1 - ESC

Here in Stockholm, the ESC conference is finally underway. It's being billed as the largest conference for cardiology in the world and I can believe that. The lines were brutal and many sessions (satellite symposia) were standing room only. I guess this is a good thing and means that the economy hasn't stopped people travelling to these meetings. The first 2 random cardiologists I spoke to were from Buenos Aires and the Philippines - this is truly an international meeting.

I attended an excellent imaging symposium sponsored by Toshiba. There was a focus on echo, particularly speckle tracking of LV and RV function. This was particularly useful in helping to interpret stress echo studies, where subtle wall motion abnormalities can be picked up more easily than with the eye. One great example was to use speckle tracking echo as a gatekeeper to coronary angiography in patients referred for 'cardiac clearance' prior to major non-cardiac surgery.

David Newby from Edinburgh, UK discussed the use of CT as a one-stop shop for coronary angiography, scar and perfusion imaging. This seemed possible, although at 40 minutes the study times are long - approaching a cardiac MR study. The issue of radiation is also a concern, although studies are possible with under 4mSv using the Toshiba 320 detector machine.

After this, food was called for - see below - any help much appreciated with translating what I actually ate!

Preview of ESC 2010 in Stockholm

I'm getting ready to attend the ESC meeting from Aug 28th - Sept 1st in Stockholm. We are planning high levels of coverage here on Medscape and also on our sister site attheheart.org. I'll be writing a daily blog, and giving real-time updates via Twitter (@jhfrudd). The Medscape Cardiology Facebook page will be another source of information. Last year's ESC Congress in Barcelona attracted almost 32,000 registered participants (as well as 750 registered press), making it the largest medical meeting in the world; this year's event promises a similar attendance, and a similar opportunity for reporting developments of major public health importance.

I'm giving a talk concerning the molecular imaging of atherosclerosis in a session on Monday (Imaging of Atherosclerotic Plaques - Newer Trends and Developments). I plan to cover PET imaging of atherosclerosis in depth. My co-speakers (Prof Zahi Fayad, Prof Jagat Narula and Prof Kaufman) will cover CT, MRI and ultrasound and this promises to be an in depth view of both current practice and likely direction of vascular imaging.

I plan to attend Hotline session where the full STAR trial results will be presented - this study administered intra-coronary stem cells to over 180 heart failure patients. Although some data has been published already, the long term effects of this therapy, particularly on mortality and quality of life are potentially of large clinical impact.

There are also several LIVE sessions that look outstanding - particularly the rapid assessment of atherosclerosis session from Liege on 29th August (IMT, EF and Calcium score).

Controversies in Cardiac CT promises to be an explosive session, with battles over calcium scoring in symptomatic subjects (should we?) and radiation concerns.

I always look forward to high tech sessions and there is one that I will attend on robotic surgery in both atrial fibrillation ablation and CABG.

So join me in either attending in person or remotely via this blog, twitter, facebook and our daily conference updates from Stockholm.

What sessions are you particularly looking forward to? Do you think the coverage on medical media is now so great that it's less important to attend in person?

How To Optimise Cardiac CT Studies

1. Breath holding practice before imaging

2. Administer GTN before imaging

3. Slow heart rate to below 60 beats/min

4. Use a high contrast flow rate (at least 5mls/sec, preferably 6 or 7mls/sec)

Anyone else have any tips about CT to share in the comments?

Screening For Lp(a) - Now Recommended by the European Atherosclerosis Society

This post on HeartWire caught my eye. At the recent EAS meeting, it was announced that a statement is forthcoming, supporting a screening blood test for Lp(a) - and then therapy with nicotinic acid to lower levels below 50mg/dL. This recommendation is aimed at those at intermediate and high risk of CV disease.

However, as the authors state further down the page:

"Since lifestyle appears to have little impact on an individual's Lp(a) level, the EAS consensus panel recommends that 1 to 3 g of niacin (nicotinic acid) daily is the best treatment for lowering Lp(a) levels. However, the group acknowledges that there have not been randomized, controlled trials selectively targeting plasma levels of Lp(a) and calls for further studies in both primary- and secondary-prevention settings to better define which patients should be targeted for treatment and what the target level of Lp(a) should be."

Where do you stand on this? Are you comfortable to screen and treat this 'risk factor' in the absence of clinical end point evidence?

Let us know your plans regarding Lp(a) below!

Addressing Cardiovascular Risk Factors in Middle Age Reduces Dementia Risk

A couple of recent papers related to vascular risk and dementia of interest.

If we act in middle age, we can reduce dementia rates. We know that acting in later life is too late;the damage has already been done.

One study (Wolozin et al, Boston, BMJ) showed that taking an angiotensin receptor antagonist drug led to a 55% reduction in the incidence of Alzheimer's disease and vascular dementia, in comparison with a group taking non-ARB CV drugs.

Another study from Edinburgh, UK, modelled the effect on dementia of targeting four risk areas (obesity, hyperlipidaemia, hypertension and exercise). If treatment were begun from age 35 onwards, a reduction in dementia prevalence of the order of 20% might be possible (Russ and Starr, Clinical Evidence 2010).

These studies seem heartening, although the 'number needed to treat' is likely to be high and difficult to quantify.

Do you think that poly-pharmacy is a price worth paying? Would you take 3 pills a day for 50 years? Who will pay?

Let us know your thoughts below in the comments.

Short-term Impact of Smoke-free Legislation in England : 1200 Fewer MIs Per Year

I thought I'd share a few interesting links and abstracts over the next few weeks, rather than the longer more detailed posts that I've been producing recently.

Here's one for starters : a study showing that the smoking ban (introduced across England in 2007) resulted in a 2% reduction in myocardial infarctions - 1200 fewer admission per year, compared to the years before the ban.

Has this work been replicated in US states with a smoking ban?

What are your thoughts?

BMJ paper

More prognostic data for cardiac CT and the limitations of virtual histology

As a follow up to a post here in December 2009, another paper confirming the prognostic ability of cardiac CT was just published in Circulation Cardiovascular Imaging (Russo et al, May 11th).

In a series of 441 patients imaged using 16 detector CT, the best predictor of events was a combination of risk score + calcium score + CT angiogram findings. Follow-up up was 32 months on average, and the number of hard CV events was 44.

Significant CAD on CT confered an annual event rate of 8.1%, mild CAD 3.9% and normal coronary arteries on CT meant a risk level very similar to that following a normal perfusion scan - 0.9% per year.

In the same Journal, Thim and colleagues tackled a related coronary issue, that of the reliable identification of necrotic core size in atheroma. This is thought to be related to risk of future CV events. They used an intravascular approach, IVUS-VH (virtual histology) and compared the findings with direct histology in a porcine model of atherosclerosis.There was no relationship at all between the true histology and the virtual histology findings.

I've discussed IVUS-VH before, in terms of the PROSPECT study.

What are your views on these two papers? Should we move away from intravascular coronary assessment towards a non-invasive imaging paradigm? Is the pig model of atheroma a reliable surrogate for human coronary disease (the IVUS-VH algorithm was based on human coronary lesions).

Let us know your views in the comments please.

Predicting MI - Risk factors or Disease detection?

Most patients presenting to the ED with an MI have at least 1 cardiovascular risk factor, contrary to the popular opinion that MIs come out of nowhere. This has been demonstrated in the MRFIT study (Greenland et al, JAMA, 2003), where >87% of those with fatal MI had exposure to at least one risk factor.

The Interheart study (Yusuf et al, Lancet, 2004) showed that this was the case in countries around the globe, in both sexes and across age groups. Collectively, the big nine risk factors accounted for 90% of the MI risk in men and 94% in women.

On the contrary, the predictive power of risk factors alone to determine future events in asymptomatic people is low. The likelihood ratio for CHD death with >1 risk factor is only 1.31 in males and 1.39 in females, based on the 3 studies cited by Greenland in the 2004 paper above (Weissler JAMA 2004 vol. 291 (3) pp. 299-300; author reply 300-1).

It's easy to see why - most people with risk factors don't end up with an MI.

For example, take cholesterol : MRFIT (Circulation 1991) showed a strong correlation between total cholesterol level and 10 year CHD death rate. Trouble is, 60% of all CHD deaths occur in people with total cholesterol levels below 240mg/dL (that's about 75% of the population).

From the AFCAPS/TexCAPS trial we saw that statin therapy in those with low CRP and LDLs under 150mg/dL did nothing, whereas treating those with LDLs under 150mg/dL and hsCRP >2mg/dL had a benefit. JUPITER was designed to explore this further, testing whether statin therapy would lower event rates in this patient cohort. This was a very positive trial in favor of lowering inflammation, raising the question of whether or not we should be routinely checking hsCRP in our patients.

Similar story exists for high blood pressure : in a meta-analysis of >1 million adults without vascular disease, published in the Lancet in 2002 by the Prospective Studies Collaboration, there was a strong and direct correlation between both systolic and diastolic blood pressure and CHD death. But same issue with prediction as with lipids : 80% overlap in diastolic BP distributions of those who die and don t die of IHD (Wald, Law BMJ 2003; 326:1419-23).

Where does this leave us?

1. Add more risk factors into our scoring systems in an attempt to improve them? CRP is proving controversial (http://www.medscape.com/viewarticle/705124) in this respect.

Most of us likely don't actually use these algorithms anyway (Fuster, V editorial, Nature Reviews Cardiology August 2009).

1. How about testing for subclinical disease? Calcium scoring, carotid IMT measurement, vascular reactivity etc. The SHAPE guidelines suggest this is more cost-effective than population risk factor modification because it's targeting the therapy to those most at risk (http://www.shapesociety.org/three_steps_to_get_in_shape/).

The US Preventative Services Task Force report thinks not : (http://www.ahrq.gov/clinic/uspstf/uspscoronaryhd.htm#jmp0).

1. How about we just identify and treat the conventional risk factorsand not search for disease in those who are asymptomatic?

This debate has been raging for years - what's your view? Feel free to leave a comment!

Incorporating Genetics Into Drug Dosing and Risk Prediction - Ready for Prime Time?

Are we ready to roll out genetic testing to our cardiovascular disease patients?

One of the interesting sessions that I plan to attend at ACC 2010 is where the results of the Medco-Mayo Warfarin Effectiveness Study (MM-WES) trial are being announced.

This large study (>1000 subjects) has compared two warfarin dosing strategies with historical controls. In one arm, subjects have their warfarin dose adjusted along standard lines. In the genetic testing arm, patient genotype is considered and warfarin dosing proceeds according to this. It s known that polymorphisms in the CYP 2C9 gene are associated with more potent anticoagulation because of reduced warfarin metabolism. This can potentially mean more episodes of clinically important bleeding. This trial is the first to determine whether prior knowledge of a patient s CYP 2C9 allele (and another, related polymorphism of VKORC1) will improve thromboembolic and bleeding rates and thereby patient safety and healthcare costs, specifically over a 6 month period.

Another study that focussed on genetic testing for determining cardiovascular risk was recently published in JAMA by Paynter and colleagues (http://jama.ama-assn.org/cgi/content/abstract/303/7/631). The authors asked whether genetic testing added anything to cardiovascular risk prediction over and above simple scoring algorithms. Many genetic markers of risk have been identified over the last decade using GWAS techniques; what is unknown is the added benefit of their knowledge for risk prediction.

In over 19,000 women, 101 SNPs known to be associated with an increased risk of CV disease were measured. In this study, over the 12 year follow-up, genetic risk scoring did not improve either discrimination or reclassification compared with ATP-111 scoring. In fact, simple family history of cardiovascular disease had the most predictive power.

This study, and another one by the same group that examined a common SNP at chromosome 9p21 (http://www.theheart.org/article/936391.do) have been widely discussed, including by Heartwire genetic expert Dr Eric Topol (http://www.theheart.org/article/1048055.do). The main issue seems to be that the JAMA study did not examine more SNPs, particularly those for Lp(a), or low frequency SNPs.

So what are your views? Is genetic testing either for directing drug therapy or to predict risk a little premature? Should we be smarter in our searches? Are low frequency SNPs the flecks of gold in the dark mysterious river of risk factors?

Automatic For The People - Cardiac CT Reads Without Human Interaction?

One of the challenges of using cardiac CT to rule out coronary artery disease is the availability of suitably qualified people to read the studies, especially outside of the working day. Researchers from Beth Israel Deaconess Medical Center, Boston, MA recently described an automated software approach to CT reads, and presented the results at the 2009 RSNA meeting (http://www.theheart.org/article/1030325.do).

They trialled the COR Analyzer (Rcadia Medical Imaging, Auburndale, MA, http://www.rcadia.com/), a cardiac CT analyzing system that works without human input from the raw data. The study involved CT datasets from 115 patients at low to intermediate risk of CAD imaged in the ER. Of the 100 analyzable studies, compared to two expert CT readers, the algorithm’s negative predictive value was 98%, its sensitivity was 83% and specificity was 82%. The ‘black’ box’ correctly identified only 5 of the 6 patients with significant obstructive coronary disease; a result which to me means that further refinements to the algorithm must be made.

The same system was also tested in a different population of patients in a study published in November 2009 in European Radiology (http://www.springerlink.com/content/aml5708k1147r547/). This time, an X-ray coronary angiogram was used as the gold standard. A population with either chest pain or an abnormal nuclear perfusion study was chosen. The COR Analyzer pulls out from the CT dataset curved MPRs for all four main coronary arteries and highlights those where stenosis is suspected, or where it believes there has been a technical failure of acquisition or processing. Results were similar to the RSNA study; high negative predictive values at the patient level, but of note the system missed ⅔ significant stenoses of the left main coronary artery.

Considering these findings, the algorithm in its current form seems best placed to aid ruling out of CAD in patients a with low likelihood of disease. Do you agree?

What do you think of computer aided diagnostics? We’ve seen it applied in other areas of medicine - EKG reads, CT colonography and for automatic detection of pulmonary emboli on CT.

Do you use this kind of technology in your practice?

Would you be happy to ‘hand-over’ diagnostics to a black box?