Topolog : News and views from Eric J. Topol http://blogs.theheart.org/topolog Eric J. Topol editor in chief of theheart.org and Dean of Scripps School of Medicine, translate clinical research in cardiology to daily practice. Cardiologist, Dr Eric Topol, Editor-in-chief, theheart.org and Director, Scripps Translational Science Institute, translates clinical research in cardiology to daily practice. en-us theheart.org theheart.org info@theheart.org http://blogs.theheart.org/images/topolog/rss_banner_url.jpg Cardiologist, Dr Eric Topol, Editor-in-chief, theheart.org and Director, Scripps Translational Science Institute, translates clinical research in cardiology to daily practice. http://blogs.theheart.org/topolog Taking point-of-care genetic testing closer to mainstream Topolog info@theheart.org The first rapid point-of-care genotyping randomized clinical trial in cardiology--although small--demonstrated striking results and is another indication of the future role of genetic testing in cardiovascular practice.<img src="http://feeds.feedburner.com/~r/Topolog/~4/BwUcYv_Qu5M" height="1" width="1"/> The first rapid point-of-care genotyping randomized clinical trial in cardiology—although small—demonstrated striking results and is another indication of the future role of genetic testing in cardiovascular practice.

What are your thoughts?

See also:

RAPID GENE: Point-of-care genetic test singles out clopidogrel nonresponders

Roberts JD, Wells GA, Le May MR, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): A prospective, randomised, proof-of-concept trial. Lancet 2012; DOI:10.1016/S01406736(12)60161-5. Available at: http://www.thelancet.com.

]]> Wed, 11 Apr 2012 09:27:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/BwUcYv_Qu5M/taking-pointofcare-genetic-testing-closer-to-mainstream http://blogs.theheart.org/topolog/2012/4/11/taking-pointofcare-genetic-testing-closer-to-mainstream http://blogs.theheart.org/topolog/2012/4/11/taking-pointofcare-genetic-testing-closer-to-mainstream#comments Topolog http://blogs.theheart.org/images/thumbnails/taking-pointofcare-genetic-testing-closer-to-mainstream.jpg 4 http://blogs.theheart.org/topolog/2012/4/11/taking-pointofcare-genetic-testing-closer-to-mainstream Statins and diabetes: A hard look at the data Topolog info@theheart.org The data are clear: in primary prevention, when comparing the benefit in preventing heart attack, stroke, and death vs the risk of diabetes, the trade-off is very slim--and the dangers, very real.<img src="http://feeds.feedburner.com/~r/Topolog/~4/YX9o5AJnrac" height="1" width="1"/> The data are clear: in primary prevention, when comparing the benefit in preventing heart attack, stroke, and death vs the risk of diabetes, the trade-off is very slim—and the dangers, very real.

See also:

FDA adds warnings to statin label

The Diabetes Dilemma for Statin Users

The creative destruction of medicine: How the digital revolution will create better healthcare

Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011; 305:2556-2564. Abstract.

Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359:2195-207. Abstract.

Sattar N, Preiss D, Murray H, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375:735-742. Abstract.

Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial. Lancet 2002; 60:7-22. Abstract.

]]> Thu, 01 Mar 2012 17:25:00 -0500 http://feedproxy.google.com/~r/Topolog/~3/YX9o5AJnrac/statins-and-diabetes-a-hard-look-at-the-data-2 http://blogs.theheart.org/topolog/2012/3/1/statins-and-diabetes-a-hard-look-at-the-data-2 http://blogs.theheart.org/topolog/2012/3/1/statins-and-diabetes-a-hard-look-at-the-data-2#comments Topolog http://blogs.theheart.org/images/thumbnails/statins-and-diabetes-a-hard-look-at-the-data-2.jpg 43 http://blogs.theheart.org/topolog/2012/3/1/statins-and-diabetes-a-hard-look-at-the-data-2 Talking about a (healthcare) revolution: The digital age ushers in precision medicine Topolog info@theheart.org The digital age is revolutionizing the healthcare paradigm by replacing an archaic and wasteful population-based model with precision medicine.<img src="http://feeds.feedburner.com/~r/Topolog/~4/Q2-DhStMA-o" height="1" width="1"/> The digital age is revolutionizing the healthcare paradigm by replacing an archaic and wasteful population-based model with precision medicine. Technology now enables us to digitize the human being. Is the medical community flexible enough to accept change? What are your thoughts?

See also:

Mirnezami R, Nicholson J, Darzi A. Preparing for precision medicine. N Engl J Med 2012; DOI:10.1056/NEJMp1114866. Available here. 

The creative destruction of medicine: How the digital revolution will create better healthcare

Combining wireless sensors and genomics for CVD prevention?

 

]]> Wed, 25 Jan 2012 11:25:00 -0500 http://feedproxy.google.com/~r/Topolog/~3/Q2-DhStMA-o/talking-about-a-healthcare-revolution-the-digital-age-ushers-in-precision-medicine http://blogs.theheart.org/topolog/2012/1/25/talking-about-a-healthcare-revolution-the-digital-age-ushers-in-precision-medicine http://blogs.theheart.org/topolog/2012/1/25/talking-about-a-healthcare-revolution-the-digital-age-ushers-in-precision-medicine#comments Topolog http://blogs.theheart.org/images/thumbnails/talking-about-a-healthcare-revolution-the-digital-age-ushers-in-precision-medicine.jpg 9 http://blogs.theheart.org/topolog/2012/1/25/talking-about-a-healthcare-revolution-the-digital-age-ushers-in-precision-medicine An important miscue in clopidogrel pharmacogenomics Topolog info@theheart.org Dr Matthew Price joins Dr Eric Topol to counter the paper published by Dr Holmes and colleagues, which questions clopidogrel platelet-function testing and genotyping and their relationship with clinical outcomes.<img src="http://feeds.feedburner.com/~r/Topolog/~4/Eaw2Ez95hPI" height="1" width="1"/> In the December 28, 2011 issue of the Journal of the American Medical Association, Holmes and colleagues publish what they label as a "systematic review and meta-analysis" of clopidogrel CYP2C19 genotyping, platelet function, and cardiovascular events [1]. There has been no shortage of meta-analyses of clopidogrel platelet-function testing and genotyping and their relationship with clinical outcomes [1,2,3].

But the current one is remarkably misleading. While it reviews data from 32 studies in over 42 000 patients, the conclusion is that "there was no significant association of genotype with cardiovascular events." This conclusion is directly contradicted by the data presented, showing a significant and highly consistent excess of stent thrombosis in patients with a loss-of-function CYP2C19 allele. The absolute increase of stent thrombosis was 14 per 1000 individuals. With over one million patients undergoing coronary stenting per year in the US, this extrapolates to over 14 000 stent-thrombosis events per year.

Stent thrombosis results in either death or heart attack. In a prior meta-analysis by Mega and colleagues who studied 9685 patients undergoing coronary stenting, the stent thrombosis hazard ratio among carriers of a loss-of-function CYP2C19 allele was 2.67 and for homozygotes it was 3.97. Beyond stent thrombosis, there was also a significant excess of death, MI, and stroke for either carriers or homozygotes [2]. Similarly, in an analysis by Hulot and colleagues among 4905 patients who had coronary intervention, there was an odds ratio of 3.45 for stent thrombosis for individuals carrying a loss-of-function CYP2C19*2 allele [3].

Accordingly, a critical flaw of the analysis by Holmes and colleagues was the lack of testing for heterogeneity among patients who underwent stenting as compared with those treated medically. No data for a genotype-by-treatment (medical vs stenting) interaction was provided. The analysis includes a large number of patients from trials that had nothing to do with coronary stenting (eg, atrial fibrillation or STEMI patients treated with thrombolytics) and assess outcomes where the benefit of clopidogrel itself is dubious (eg, target vessel revascularization). Instead of acknowledging the prior extensive body of work that unequivocally documents the stent thrombosis liability for patients who do not metabolize clopidogrel normally, the authors ignored this and homogenized the data, resulting in an erroneous and sweeping conclusion. In fact, all of the prior work on clopidogrel pharmacogenomics has demonstrated the CYP2C19 loss-of-function variants to be important only in coronary stenting patients and does not show up in those medically treated.  It makes perfect sense that a metal implant in a coronary artery would pose a particular vulnerability to inadequate platelet suppression.

At Scripps, Vanderbilt, Pitié-Salpetrière in Paris, and other centers, the use of genotyping and platelet function testing for patients receiving clopidogrel is restricted to those undergoing stenting. We and others in the genomic medicine community consider this practice to represent the prototype of pharmacogenomics for several key reasons. First, we have long known that the pharmacologic response to clopidogrel, as reflected by platelet suppression, is particularly heterogeneous. Second, the only consistent DNA sequence variants that have been demonstrated to be associated with the heterogeneous response are localized to the principal cytochrome involved in clopidogrel's metabolism—CYP2C19. Third, the risk of a stent thrombosis with even one loss-of-function variant is high, consistently two- to threefold across all of the studies that have focused on this end point; similar risks have been observed with platelet-function testing. Fourth, since almost all patients with stent thrombosis will either die or have a heart attack as a result, it is vital to prevent these events. Fifth, the genotypic data are particularly actionable—using alternative dosing regimens of clopidogrel [4] or alternative P2Y12-receptor antagonists, either prasugrel or ticagrelor, both of which are commercially available and bypass the CYP2C19 metabolic–pathway concerns. And sixth, the response of clopidogrel for individualizing the treatment regimen can be corroborated and titrated with bedside platelet-function testing.

The accompanying editorial to the paper by Holmes et al concludes that "physicians should use CYP2C19 or platelet-reactivity testing rarely, if ever" and that there has been "overzealous adoption" [5]. The editorialist advocates a large randomized controlled study. While such trials would always be useful, it unfortunately is a fantasy: it would require tens of thousands of patients, there is no entity that would support such a trial, and the reality is that we have both compelling data and millions of patients who are undergoing coronary stenting around the world each year. Moreover, the era of individualized medicine needs to transcend megatrials of populations, which are not only unsustainable but also crowd out the benefits that can be exceptionally important and validated for the individual patient [6]. All best efforts to prevent stent thrombosis need to be implemented in clinical practice. Refinements that are actively being pursued include point-of-care genotyping to make this much more rapid and inexpensive, along with more complete definition of genomic markers defined by exome and whole-genome sequencing.

Eric J Topol MD

Paul S Teirstein MD

Matthew Price MD

Scripps Clinic, La Jolla, CA

Dan Roden MD

Vanderbilt University, Nashville, TN

Gilles Montalescot MD

Hôpital Pitié-Salpetrière, Paris, France

References:

1.    Holmes MV, Perel P, Shah T, et al. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events. JAMA 2011; 306:2704-2714.

2.    Mega JI, Simon T, Collet JP et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI. JAMA 2010; 304:1821-1830. Available here.

3.    Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk of clopidogrel treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pimp inhibitor coadministration: A systematic meta-analysis. J Am Coll Cardiol 2010; 56:134-143. Available here.

4.    Mega JL, Hochholzer W, Frelinger AL, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect of platelet reactivity in patients with stable cardiovascular disease. JAMA 2011; 306:2221-2228. Available here.

5.    Nissen SE. Pharmacogenomics and clopidogrel. JAMA 2011; 306:2727-2728.

6.    Topol EJ. The Creative Destruction of Medicine; New York: Basic Books, 2012.

See also:

]]> Tue, 27 Dec 2011 16:00:00 -0500 http://feedproxy.google.com/~r/Topolog/~3/Eaw2Ez95hPI/miscue-in-clopidogrel-pharmacogenomics http://blogs.theheart.org/topolog/2011/12/27/miscue-in-clopidogrel-pharmacogenomics http://blogs.theheart.org/topolog/2011/12/27/miscue-in-clopidogrel-pharmacogenomics#comments Topolog http://blogs.theheart.org/images/thumbnails/miscue-in-clopidogrel-pharmacogenomics.jpg 13 http://blogs.theheart.org/topolog/2011/12/27/miscue-in-clopidogrel-pharmacogenomics Big-time progress in cardiovascular genomics Topolog info@theheart.org Two important recent studies--pertaining to Sporadic Thoracic Aortic Aneurysms and Dissections (STAAD) and hypertension--point to remarkable progress in the realm of genomic research.<img src="http://feeds.feedburner.com/~r/Topolog/~4/ejq_MQep0Hc" height="1" width="1"/> Two important recent studies--pertaining to Sporadic Thoracic Aortic Aneurysms and Dissections (STAAD) and hypertension--point to remarkable progress in the realm of genomic research and pave the way to better understanding of cardiovascular disease and improved treatment options.

How do you think this genomic research will add to our understanding of CV disease?

See also:

 

]]> Tue, 11 Oct 2011 13:05:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/ejq_MQep0Hc/cardiovascular-breakthroughs-in-genomics http://blogs.theheart.org/topolog/2011/10/11/cardiovascular-breakthroughs-in-genomics http://blogs.theheart.org/topolog/2011/10/11/cardiovascular-breakthroughs-in-genomics#comments Topolog http://blogs.theheart.org/images/thumbnails/cardiovascular-breakthroughs-in-genomics.jpg 1 http://blogs.theheart.org/topolog/2011/10/11/cardiovascular-breakthroughs-in-genomics Novel anticoagulants: Is this the best we can do? Topolog info@theheart.org Despite being a positive and significant trial, ARISTOTLE demonstrated the benefit of apixaban compared with warfarin in only 29 patients out of 1000. What about the remaining 971 people?<img src="http://feeds.feedburner.com/~r/Topolog/~4/Mp9T4dWel5k" height="1" width="1"/> Despite being a positive and significant trial, ARISTOTLE demonstrated the benefit of apixaban compared with warfarin in only 29 patients out of 1000. What about the remaining 971 people?

In an era of healthcare crisis and prolonged economic uncertainty, does the small margin of benefit shown in trials such as ARISTOTLE, RE-LY, and ROCKET-AF justify their cost?

What are your thoughts on the role of mega trials? Have you adopted the new oral factor Xa inhibitors in your practice?

See:

]]> Mon, 12 Sep 2011 11:45:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/Mp9T4dWel5k/novel-anticoagulants-is-this-the-best-we-can-do-2 http://blogs.theheart.org/topolog/2011/9/12/novel-anticoagulants-is-this-the-best-we-can-do-2 http://blogs.theheart.org/topolog/2011/9/12/novel-anticoagulants-is-this-the-best-we-can-do-2#comments Topolog http://blogs.theheart.org/images/thumbnails/novel-anticoagulants-is-this-the-best-we-can-do-2.jpg 3 ESC 2011 ESC 2011 http://blogs.theheart.org/topolog/2011/9/12/novel-anticoagulants-is-this-the-best-we-can-do-2 What purpose does the IMT measurement serve? Topolog info@theheart.org As the measurement of intima-media thickness gathers traction, it's time to ponder whether this test is really worthwhile.<img src="http://feeds.feedburner.com/~r/Topolog/~4/pV_6_nBW2cs" height="1" width="1"/> In their exemplary recent study published in the NEJM Polak et al conclude that IMT measurement makes a statistically significant improvement to risk classification. But as the measurement of intima-media thickness gathers traction, it's time to ponder whether this test is really worthwhile.

What are your thoughts on measuring IMT?

See:

Polak J, Pencina M, Pencina K, et al. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med 2011; 365:213-221. Abstract.

Internal carotid IMT slightly improves risk classification

]]> Tue, 09 Aug 2011 16:00:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/pV_6_nBW2cs/what-purpose-does-the-imt-measurement-serve http://blogs.theheart.org/topolog/2011/8/9/what-purpose-does-the-imt-measurement-serve http://blogs.theheart.org/topolog/2011/8/9/what-purpose-does-the-imt-measurement-serve#comments Topolog http://blogs.theheart.org/images/thumbnails/what-purpose-does-the-imt-measurement-serve.jpg 21 http://blogs.theheart.org/topolog/2011/8/9/what-purpose-does-the-imt-measurement-serve AliveCor app transforms your iPhone into an ECG: Watch my demo! Topolog info@theheart.org Revolutionary new technology--developed by Dr David Albert and pending FDA approval--brings heart monitoring closer to home and onto your iPhone. See how easy it is to use, and watch as I take the device for a test drive.<img src="http://feeds.feedburner.com/~r/Topolog/~4/UUn2eT9XT44" height="1" width="1"/> Revolutionary new technology—developed by Dr David Albert and pending FDA approval—brings heart monitoring closer to home and onto your iPhone. See how easy it is to use, and watch as I take the device for a test drive.

Disclosure: I have no relationship with AliveCor.

See:

Dr David Albert's demo on YouTube

AliveCor

]]> Wed, 22 Jun 2011 10:15:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/UUn2eT9XT44/alivecor-app-transforms-your-iphone-into-an-ecg-watch-my-demo http://blogs.theheart.org/topolog/2011/6/22/alivecor-app-transforms-your-iphone-into-an-ecg-watch-my-demo http://blogs.theheart.org/topolog/2011/6/22/alivecor-app-transforms-your-iphone-into-an-ecg-watch-my-demo#comments Topolog http://blogs.theheart.org/images/thumbnails/alivecor-app-transforms-your-iphone-into-an-ecg-watch-my-demo.jpg 26 http://blogs.theheart.org/topolog/2011/6/22/alivecor-app-transforms-your-iphone-into-an-ecg-watch-my-demo Why has dabigatran uptake been disappointing? Topolog info@theheart.org With strong evidence to support the use of the drug, what explains its relatively poor uptake? What are your reasons for not prescribing dabigatran?<img src="http://feeds.feedburner.com/~r/Topolog/~4/TXUktj2aSEk" height="1" width="1"/> Researchers worked for decades to find a replacement for warfarin—that drug that we love to hate—until dabigatran arrived on the scene and caused widespread excitement. With strong evidence to support the use of the drug, what explains its relatively poor uptake? What are your reasons for not prescribing dabigatran?

See:

Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011; 123:2562-2570. Available here.

Avorn J. The relative cost-effectiveness of anticoagulants. Obvious, except for the cost and the effectiveness. Circulation 2011; 123:2519-2521. Available here.

Dabigatran cost-effectiveness in AF tied to patient stroke and bleeding risks

]]> Thu, 09 Jun 2011 09:30:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/TXUktj2aSEk/why-aren-t-you-prescribing-dabigatran http://blogs.theheart.org/topolog/2011/6/9/why-aren-t-you-prescribing-dabigatran http://blogs.theheart.org/topolog/2011/6/9/why-aren-t-you-prescribing-dabigatran#comments Topolog http://blogs.theheart.org/images/thumbnails/why-aren-t-you-prescribing-dabigatran.jpg 25 http://blogs.theheart.org/topolog/2011/6/9/why-aren-t-you-prescribing-dabigatran Recognizing the legendary accomplishments of Dr Arthur Moss Topolog info@theheart.org A master clinician, teacher, and researcher, Dr Moss's numerous accomplishments--worthy of wide recognition--have helped advance cardiology for over 50 years.<img src="http://feeds.feedburner.com/~r/Topolog/~4/uj0ULwfrWoE" height="1" width="1"/> Dr Arthur Moss: MADIT and much more
Dr Arthur Moss: MADIT and much more

Few individuals have contributed to the field of cardiovascular medicine as Dr Arthur Moss has. A master clinician, teacher, and researcher, Dr Moss's numerous accomplishments--worthy of wide recognition--have helped advance cardiology for more than 50 years.

See:

MADIT-CRT: Resynchronization therapy cuts heart-failure risk in patients with only mild disease

To view Dr Arthur Moss's page at the University of Rochester, click here.

To read the commencement address for University of Rochester School of Medicine and Dentistry, click here.

]]> Thu, 19 May 2011 11:10:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/uj0ULwfrWoE/recognizing-the-ongoing-accomplishments-of-dr-arthur-moss-2 http://blogs.theheart.org/topolog/2011/5/17/recognizing-the-ongoing-accomplishments-of-dr-arthur-moss-2 http://blogs.theheart.org/topolog/2011/5/17/recognizing-the-ongoing-accomplishments-of-dr-arthur-moss-2#comments Topolog http://blogs.theheart.org/images/thumbnails/recognizing-the-ongoing-accomplishments-of-dr-arthur-moss-2.jpg 2 http://blogs.theheart.org/topolog/2011/5/17/recognizing-the-ongoing-accomplishments-of-dr-arthur-moss-2 Medical errors: Still made in one out of four hospitalized patients Topolog info@theheart.org The April edition of Health Affairs tackles the issue of error in medical practice, which is estimated to cause the death 100 000 patients and cost $17 billion annually, despite a decade of quality initiatives. How can we stop medical error?<img src="http://feeds.feedburner.com/~r/Topolog/~4/sckt8o7NdOc" height="1" width="1"/> The April edition of Health Affairs tackles the issue of error in medical practice, which is estimated to cause the death 100 000 patients and cost $17 billion annually, despite a decade of "quality" initiatives. As a healthcare professional, do these statistics shock you? Or do they seem plausible based on your practice? What are your recommendations for stopping medical error? Is the hospital still the antechamber to the tomb?

See:

Dentzer S. Still crossing the quality chasm—or suspended over it? Health Aff 2011; 30:4554-4555. Available here.

Landrigan CP, Parry GJ, Bones CB, et al. Temporal trends in rates of patient harm resulting from medical care. N Engl J Med 2010; 363:2124-2134. Available here.    

]]> Tue, 19 Apr 2011 13:50:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/sckt8o7NdOc/medical-errors-still-present-in-1-out-of-4-consults http://blogs.theheart.org/topolog/2011/4/19/medical-errors-still-present-in-1-out-of-4-consults http://blogs.theheart.org/topolog/2011/4/19/medical-errors-still-present-in-1-out-of-4-consults#comments Topolog http://blogs.theheart.org/images/thumbnails/medical-errors-still-present-in-1-out-of-4-consults.jpg 18 http://blogs.theheart.org/topolog/2011/4/19/medical-errors-still-present-in-1-out-of-4-consults Colleagues, do we need to order 20 million echocardiograms a year? Topolog info@theheart.org As the economic crisis continues, we cardiologists should be reigning in costs and helping to reduce spiraling healthcare expenses. Do you need that echocardiogram?<img src="http://feeds.feedburner.com/~r/Topolog/~4/QC8y-rGaMVw" height="1" width="1"/> As the economic crisis continues, we cardiologists should be reigning in costs and helping to reduce spiraling healthcare expenses. Do you need that echocardiogram?

 See:

Echo system in your pocket: Rich in potential, niche uses for now

Extraordinary use of nuclear scintigraphy

]]> Wed, 16 Mar 2011 11:25:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/QC8y-rGaMVw/colleagues-do-we-need-to-order-20-million-echocardiograms-a-year http://blogs.theheart.org/topolog/2011/3/16/colleagues-do-we-need-to-order-20-million-echocardiograms-a-year http://blogs.theheart.org/topolog/2011/3/16/colleagues-do-we-need-to-order-20-million-echocardiograms-a-year#comments Topolog http://blogs.theheart.org/images/thumbnails/colleagues-do-we-need-to-order-20-million-echocardiograms-a-year.jpg 32 http://blogs.theheart.org/topolog/2011/3/16/colleagues-do-we-need-to-order-20-million-echocardiograms-a-year Creating cardiac diseases in a dish using pluripotent stem cells Topolog info@theheart.org Fascinating research using induced pluripotent stem cells has effectively allowed researchers to create "diseases in a dish." The medical implications are exciting and far-reaching: What are your thoughts?<img src="http://feeds.feedburner.com/~r/Topolog/~4/lHUpGgBeSIQ" height="1" width="1"/> Fascinating research using induced pluripotent stem cells has effectively allowed researchers to create "diseases in a dish". The medical implications are exciting and far-reaching: creating a means for researchers to recapitulate diseases and design appropriate therapies that match biologically.

What are your thoughts on this new trend for cardiovascular medicine?

See:

Itzhaki I, Maizels L, Huber I, et al. Modelling the long QT syndrome with induced pluripotent stem cells. Nature. 2011 Jan 16. Abstract.

Moretti A, Bellin M, Welling A, et al. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med. 2010 Oct 7;363(15):1397-409. Abstract.

Yazawa M, Hsueh B, Pasca AM, et al. Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature. 2011. 2011 Feb 9. Abstract.

]]> Mon, 21 Feb 2011 12:24:00 -0500 http://feedproxy.google.com/~r/Topolog/~3/lHUpGgBeSIQ/creating-cardiac-diseases-in-a-dish-using-pluripotent-stem-cells http://blogs.theheart.org/topolog/2011/2/21/creating-cardiac-diseases-in-a-dish-using-pluripotent-stem-cells http://blogs.theheart.org/topolog/2011/2/21/creating-cardiac-diseases-in-a-dish-using-pluripotent-stem-cells#comments Topolog http://blogs.theheart.org/images/thumbnails/creating-cardiac-diseases-in-a-dish-using-pluripotent-stem-cells.jpg 1 http://blogs.theheart.org/topolog/2011/2/21/creating-cardiac-diseases-in-a-dish-using-pluripotent-stem-cells Extraordinary use of nuclear scintigraphy Topolog info@theheart.org Ten million nuclear heart scans are performed per year: why are we exposing our patients unnecessarily to such a high dose of radiation?<img src="http://feeds.feedburner.com/~r/Topolog/~4/XrACCupIEec" height="1" width="1"/> A study on the use of myocardial perfusion imaging showed that patients underwent a median of 15 procedures involving radiation exposure, of which a third received cumulative doses. On the other hand, a NEJM paper showed that in a large, national registry, only 38% of patients without known heart disease who underwent elective invasive angiography had obstructive coronary artery disease.

Ten million nuclear heart scans are performed per year: why are we exposing our patients unnecessarily to such a high dose of radiation?

See:

Einstein AJ, Weiner SD, Bernheim A, et al. Multiple testing, cumulative radiation dose, and clinical indications in patients undergoing myocardial perfusion imaging.  JAMA 2010 ;304:2137-2144.

Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med 2010; 362:886-895. 

More data linking cardiac imaging to high radiation exposure

Noninvasive testing adds little to risk-factor screening for predicting obstructive CAD

]]> Fri, 07 Jan 2011 13:29:00 -0500 http://feedproxy.google.com/~r/Topolog/~3/XrACCupIEec/new-post-3-2 http://blogs.theheart.org/topolog/2011/1/7/new-post-3-2 http://blogs.theheart.org/topolog/2011/1/7/new-post-3-2#comments Topolog http://blogs.theheart.org/images/thumbnails/new-post-3-2.jpg 17 http://blogs.theheart.org/topolog/2011/1/7/new-post-3-2 Symplicity: A key to treating severe resistant hypertension Topolog info@theheart.org Impressive results from the Symplicity HTN-2 trial, which sought to treat severe resistant hypertension with renal nerve denervation, point to a new mainstay of therapy and pose a number of stimulating questions.<img src="http://feeds.feedburner.com/~r/Topolog/~4/AJXykEd8to8" height="1" width="1"/> Impressive results from the Symplicity HTN-2 trial, which sought to treat severe resistant hypertension with renal nerve denervation, point to a new mainstay of therapy and pose a number of stimulating questions: Who will perform this operation? How much will it cost? Can the (partially blind) procedure be tweaked and improved? Might treatment also be appropriate for patients with milder hypertension?

What are your thoughts on renal denervation to treat hypertension?

See:

A revolutionary road for resistant hypertension? Renal denervation in Symplicity HTN-2

Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010. Published Online: 17 November 2010. Abstract.

]]> Fri, 03 Dec 2010 11:20:00 -0500 http://feedproxy.google.com/~r/Topolog/~3/AJXykEd8to8/symplicity-a-key-to-treating-severe-resistant-hypertension-2 http://blogs.theheart.org/topolog/2010/12/3/symplicity-a-key-to-treating-severe-resistant-hypertension-2 http://blogs.theheart.org/topolog/2010/12/3/symplicity-a-key-to-treating-severe-resistant-hypertension-2#comments Topolog http://blogs.theheart.org/images/thumbnails/symplicity-a-key-to-treating-severe-resistant-hypertension-2.jpg 2 AHA 2010 AHA 2010 http://blogs.theheart.org/topolog/2010/12/3/symplicity-a-key-to-treating-severe-resistant-hypertension-2 67 stents, 28 coronary angiograms, and a crippled healthcare system Topolog info@theheart.org A recent case report in JACC of Cardiology of a 56-year-old patient with 67 stents and a history of 28 coronary angiograms is symbolic of a healthcare system that is barreling out of control fueled by outrageous costs and unbridled use of procedures.<img src="http://feeds.feedburner.com/~r/Topolog/~4/5fAp4K2P8Qo" height="1" width="1"/> A recent case report in the Journal of the American College of Cardiology of a 56-year-old patient with 67 stents and a history of 28 coronary angiograms is symbolic of a healthcare system that is barreling out of control fueled by outrageous costs and unbridled use of procedures.

Is this an example of appropriate standard of care? Should we be concerned that this case is indicative of a system that has lost its way?

See:

Khouzam RN, Dahiya R, and Schwartz R. A heart with 67 stents. J Am Coll Cardiol. 2010;56;1605. Abstract.

]]> Mon, 01 Nov 2010 14:20:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/5fAp4K2P8Qo/67-stents-28-coronary-angiograms-and-a-crippled-healthcare-system http://blogs.theheart.org/topolog/2010/11/1/67-stents-28-coronary-angiograms-and-a-crippled-healthcare-system http://blogs.theheart.org/topolog/2010/11/1/67-stents-28-coronary-angiograms-and-a-crippled-healthcare-system#comments Topolog http://blogs.theheart.org/images/thumbnails/67-stents-28-coronary-angiograms-and-a-crippled-healthcare-system.jpg 12 http://blogs.theheart.org/topolog/2010/11/1/67-stents-28-coronary-angiograms-and-a-crippled-healthcare-system PARTNER triumph takes TAVI to the next level Topolog info@theheart.org In the history of cardiovascular trials, it's rare to see an improvement in rates of survival as remarkable as those shown in the PARTNER trial, which showed a 45% reduction in death in patients randomized to transcatheter aortic-valve implantation. . .<img src="http://feeds.feedburner.com/~r/Topolog/~4/DFD_jMH6pHU" height="1" width="1"/> In the history of cardiovascular trials, it's rare to see an improvement in rates of survival as remarkable as those shown in the PARTNER trial, which showed a 45% reduction in death in patients randomized to transcatheter aortic-valve implantation (TAVI) compared with those randomized to balloon valvuloplasty plus medical therapy. These momentous results will have far-reaching implications for cardiovascular medicine and point to a bright future for TAVI, one in which patients who are candidates for aortic-valve surgery may also be candidates for the transcatheter aortic-valve approach.

What do you think about the PARTNER trial? Could TAVI become a truly viable alternative to aortic-valve surgery?

See:

Transcatheter valves slash deaths, hospitalizations vs standard care: PARTNER

Transcatheter aortic-valve implantation (TAVI): What does the future hold?  Chaired by Dr Marty Leon

]]> Thu, 23 Sep 2010 08:35:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/DFD_jMH6pHU/partner-triumph-takes-tavi-to-the-next-level http://blogs.theheart.org/topolog/2010/9/22/partner-triumph-takes-tavi-to-the-next-level http://blogs.theheart.org/topolog/2010/9/22/partner-triumph-takes-tavi-to-the-next-level#comments Topolog http://blogs.theheart.org/images/thumbnails/partner-triumph-takes-tavi-to-the-next-level.jpg 0 TCT 2010 TCT 2010 http://blogs.theheart.org/topolog/2010/9/22/partner-triumph-takes-tavi-to-the-next-level Robotic surgery is going mainstream: Watch for healthcare costs to skyrocket Topolog info@theheart.org In their paper, Drs Barbash and Glied pose a fundamental question: why adopt new technologies that have not been validated by randomized clinical trials, appear to offer no advantage to patient outcomes, and are more expensive than existing procedures?<img src="http://feeds.feedburner.com/~r/Topolog/~4/c4w5EONCWVo" height="1" width="1"/> In their recent paper, Drs Gabriel I Barbash and Sherry A Glied report on an important rise in healthcare costs due to the increasing adoption of robotic surgery. They pose a fundamental question: why adopt new technologies that have not been validated by randomized clinical trials, appear to offer no advantage to patient outcomes, and are more expensive than existing procedures?

What are your thoughts on robotic surgery? Important trail-blazing technology or unnecessary, not yet validated, and a driver of healthcare costs?

See:

Barbash GI, Glied SA. New technology and health care costs: The case of robot-assisted surgery. N Engl J Med 2010; 363:701-704. Available here.

Clinicians use robot to perform EP diagnostics and ablate atrial flutter

]]> Wed, 25 Aug 2010 09:35:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/c4w5EONCWVo/robotic-surgery-is-going-mainstream-watch-for-healthcare-costs-to-skyrocket-3 http://blogs.theheart.org/topolog/2010/8/25/robotic-surgery-is-going-mainstream-watch-for-healthcare-costs-to-skyrocket-3 http://blogs.theheart.org/topolog/2010/8/25/robotic-surgery-is-going-mainstream-watch-for-healthcare-costs-to-skyrocket-3#comments Topolog http://blogs.theheart.org/images/thumbnails/robotic-surgery-is-going-mainstream-watch-for-healthcare-costs-to-skyrocket-3.jpg 2 http://blogs.theheart.org/topolog/2010/8/25/robotic-surgery-is-going-mainstream-watch-for-healthcare-costs-to-skyrocket-3 Complex trait genomics, or why common gene variants don't fully explain disease Topolog info@theheart.org A landmark new study by Dr Robert A Hegele's team explores common and rare variants for hypertriglyceridemia and shows that a combination of multiple rare variants of common genes can help to explain heritability of disease.<img src="http://feeds.feedburner.com/~r/Topolog/~4/dl09tY_C9iU" height="1" width="1"/> A landmark new study by Dr Robert A Hegele's team at the University of Western Ontario explores common and rare variants for hypertriglyceridemia and shows that a combination of multiple rare variants of common genes can help to explain heritability of disease.

What are your thoughts on this study and the role of complex trait genomics in cardiovascular medicine?

See:

Unique study reveals "mosaic" model for triglyceride genetics 

Johansen Christopher T, Wang Jian, Lanktree Matthew B, et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nature Genetics. 25 July 2010. Abstract. 

]]> Mon, 26 Jul 2010 16:00:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/dl09tY_C9iU/complex-trait-genomics-or-why-common-gene-variants-don-t-fully-explain-disease http://blogs.theheart.org/topolog/2010/7/26/complex-trait-genomics-or-why-common-gene-variants-don-t-fully-explain-disease http://blogs.theheart.org/topolog/2010/7/26/complex-trait-genomics-or-why-common-gene-variants-don-t-fully-explain-disease#comments Topolog http://blogs.theheart.org/images/thumbnails/complex-trait-genomics-or-why-common-gene-variants-don-t-fully-explain-disease.jpg 2 http://blogs.theheart.org/topolog/2010/7/26/complex-trait-genomics-or-why-common-gene-variants-don-t-fully-explain-disease Clopidogrel, genotyping, coronary stenting, and guidelines Topolog info@theheart.org When we know that simple testing can tell us a lot about patient risk and there is a substantial data set to support testing, why do policy makers continue to ignore the importance of individualized medicine?<img src="http://feeds.feedburner.com/~r/Topolog/~4/WyQpR7r-jt8" height="1" width="1"/> In the same week that Hulot et al published a meta-analysis reporting a high risk of events for CYP2C19*2 carriers taking clopidogrel, the ACC/AHA published guidelines stating that routine genetic or platelet-function testing is not recommended when using antiplatelet therapy. When we know that simple testing can tell us a lot about patient risk and there is a substantial data set to support testing, why do policy makers continue to ignore the importance of individualized medicine? 

Disclosure: I serve as an advisor to Sanofi-Aventis, Daiichi Sankyo, and Quest Diagnostics.

See:

New meta-analysis: CYP2C19*2 carriers at higher risks of events on clopidogrel

Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor co-administration. A systematic meta-analysis. J Am Coll Cardiol 2010; 56:134-143.

No routine genetic or platelet-function testing for clopidogrel nonresponsiveness: ACC, AHA

Holmes DR, Dehmer GJ, Kaul S, et al. ACCF/AHA clopidogrel clinical alert: Approaches to the FDA "boxed warning." J Am Coll Cardiol 2010; DOI: 10.1016/j.jacc.2010.05.013. Available at: http://content.onlinejacc.org.

]]> Thu, 08 Jul 2010 14:15:00 -0400 http://feedproxy.google.com/~r/Topolog/~3/WyQpR7r-jt8/clopidogrel-genotyping-coronary-stenting-and-guidelines http://blogs.theheart.org/topolog/2010/7/8/clopidogrel-genotyping-coronary-stenting-and-guidelines http://blogs.theheart.org/topolog/2010/7/8/clopidogrel-genotyping-coronary-stenting-and-guidelines#comments Topolog http://blogs.theheart.org/images/thumbnails/clopidogrel-genotyping-coronary-stenting-and-guidelines.jpg 2 http://blogs.theheart.org/topolog/2010/7/8/clopidogrel-genotyping-coronary-stenting-and-guidelines