Category Archives: Sudden Cardiac Death

Is Coronary Calcium Scanning the Mammography of the Heart?

If you have watched The Widowmaker as suggested by the skeptical cardiologist you have likely been convinced that the developers and promoters of coronary artery calcium (CAC) scans, for the early detection of heart disease, are true heroes in the cardiology world.

These members of the “calcium club” are portrayed as unbiased self-less promoters of the prevention of heart attacks and sudden death, fighting an uphill battle against the evil procedure and money-driven forces who push coronary stents-greedy interventional cardiologists and the device, hospital and insurance industries.

A constant theme in the documentary is that CAC scanning should be to the heart what mammography is to the breast. It should be done on all patients over a certain age and should be covered by insurance.

As a non-invasive cardiologist with a strong interest in prevention, I am definitely a strong proponent of CAC scans in the right population. As the skeptical cardiologist, however, I find flaws with the mammography comparison.

Let’s review some of the established science regarding CAC scans.

What Is A CAC Scan?

coronary calcium
Coronary calcium scan from a 52 year old man I was seeing for palpitations. He had had an equivocal stress test but had a strong family history of CAD. Standard risk factors were unremarkable. As shown here, he has very extensive calcium in his coronary arteries. The left anterior descending (LAD) has lots of calcium (CA, indicated by arrows). His total score was 1798 which is at the 99th percentile for caucasian men his age. This means that his score is higher than 99% of caucasian men. Such a high score for age puts him in an extremely high risk category of heart attack and death.

The CAC scan utilizes computed tomography (CT)  X-rays, without the need for intravenous contrast, to generate a three-dimensional picture of the heart. Because calcium is very apparent on CT scans, and because we can visualize the arteries on the surface of the heart that supply blood to the heart (the coronary arteries), the CAC scan can detect and quantify calcium in the coronary arteries with great accuracy and reproducibility.

A preventive cardiologist, Dr. Arthur Agatson, who is interviewed in the film (and who is also the creator of the South Beach Diet, a low carbohydrate, high fat diet), developed a method for counting up the amount of calcium in the coronary arteries (the Agatson or calcium score).

Calcium only develops in the coronary arteries when there is atherosclerotic plaque. The more plaque in the arteries, the more calcium.

What Is The Risk Of  A High CAC Score

Multiple observational studies have shown that a high versus low calcium score is indicative of high risk for heart attack and death.

For example, a large study published in 2008 (the MESA study), followed 6,814 individuals for 3.8 years. Compared with patients with a CAC score of 0, patients with a CAC score of 101-300 had a 7.7 fold increase risk of a coronary event (heart attack). CAC score of >300 conferred almost a tenfold increase risk.

Screen Shot 2015-09-06 at 8.32.02 AMBased on data from 5 large studies and almost 15,000 patients, we can put patients with CAC score in very low to high risk categories for cardiac events over the next 10 years.

What Is The Value Of A Zero Calcium Score?

Just as important as identifying patients with advanced or premature atherosclerosis who should be getting intensive therapy  for prevention of cardiac events, is identifying those patients who may not warrant therapy.

A CAC score of zero puts a patient in an extremely low risk category.  A recent study, with the provocative title of:

A 15-Year Warranty Period for Asymptomatic Individuals Without Coronary Artery Calcium

…demonstrated that a zero calcium score confers this low risk of cardiac events for up to 15 years.

Thus, many patients, who are considered intermediate risk based on standard risk factors, do not have significant plaque by CAC score and may not need otherwise indicated statin therapy.

Mammography

The comparison of mammography to CAC scanning is appropriate in that both have created considerable controversy and are at the epicenter of discussions on the value of mass screenings in the prevention of life-threatening disease.

In contrast to CAC, mammography has been widely accepted and promoted by most professional organizations. In recent years, however, the value of mammography for all women over the age of 40 has been questioned.

In 1980, a randomized controlled trial of screening mammography and physical examination of breasts in 89, 835 women, aged 40 to 59, was initiated in Canada. It was called the Canadian National Breast Screening Study.

The findings published last year were:

Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.

Recently, the Swedish Medical Board recommended that all mammography screening be phased out in that country.

The US preventive services task force draft guidelines, updated earlier this year, will recommend screening for women aged 50-74 but not in those aged 40-49 years.

Downsides of breast cancer mammography screening include:

-Over-diagnosis: finding and treating breast cancer that would not have been a threat to the patient.

-False positives: the test identifies a possible cancer which is not subsequently confirmed. False positives lead to breast biopsies, which are not needed and often cause needless anxiety and stress.

-Radiation exposure.

Is CAC Screening The Cardiac Equivalent Of Mammography?

CAC scans differ fundamentally from mammography because atherosclerosis is a continuous and diffuse arterial process, whereas breast cancer is (most often) localized, and either present or not.

The development of atherosclerosis starts with fatty streaks in multiple arterial beds fairly early in life, followed by progressive plaque development with progressive build up of calcium in the plaques.

Thus, the CAC score ranges continuously from zero up to several thousand.

The calcium score is not subject to false positives-if calcium is detected, atherosclerotic plaque is present.

A mammogram is either abnormal, suggesting cancer and requiring a biopsy, or it is normal. There is no continuous grading of risk.

The second fundamental difference in the two disease processes is that atherosclerosis can kill suddenly without warning.

As pointed out in numerous examples in The Widowmaker, an individual can seem fit and hearty one minute, and be dead the next, from a heart attack caused by a lethal abnormal rhythm.

Breast cancer deaths on the other hand, occur slowly after diagnosis, and are generally predictable.

Nuclear Stress Tests are the Mammography of the Heart

If we are looking for a cardiac test that has characteristics similar to mammography, the nuclear stress test is much closer than CAC.

With a nuclear stress test we are using a radio tracer injected intravenously, which subsequently traverses the coronary arteries into the heart muscle. Subsequent imaging of the photons emitted by the radio tracer allows assessment of the status of blood flow down the coronary arteries.

The test is designed to identify coronary arteries with flow limiting blockages (usually >70% blocked), caused by atherosclerotic plaques. Such blockages are more likely to be causing symptoms and therefore more likely to require treatment with coronary stents or bypass surgery.

Like mammography, then, nuclear stress tests are either abnormal or normal, and when abnormal they can be falsely abnormal.

Nuclear stress tests have a very high incidence of false positives. These false positives result in invasive catheterization procedures to more directly image the arteries, and may result in inappropriate coronary stenting or bypass procedures with associated risks.

It is because of the high risk of false positives and attendant harm that in the last decade, all cardiac societies recommend against the routine use of stress testing in asymptomatic patients.

As pointed out in the Widowmaker, there is no data which suggest that stress testing improves outcomes for cardiac patients.

Stress tests by design tell us nothing about the noncritical build up of atherosclerotic plaque. You can have a normal stress test and have a huge burden of plaque in your arteries.

It is this silent build up of atherosclerosis, with sudden rupture of plaque, which results in sudden death in most cardiac patients.

What Is The Breast Cancer Equivalent Of CAC?

A CAC of the breast would identify abnormal cells as soon as they began on the presumably multi-year road to becoming a full flown cancer.

To be fully equivalent to the CAC, the breast CAC would have to have a proven treatment that could be instituted once a certain stage of cell transformation had been reached.

For atherosclerosis, that treatment is statin drugs, which are recommended for those with high risk CAC scores.

For breast cancer, the treatment of choice is mastectomy.

 Would Widespread Institution of CAC Screening Save Millions of Lives?

For mammograms based on a review of all the evidence, the US PTF concluded:

Over a 10-year period, screening 10,000 women ages 50 to 59 years will result in 8 (95% confidence interval [CI], 2 to 17) fewer breast cancer deaths, and screening 10,000 women ages 60 to 69 years will result in 21 (95% CI, 11 to 32) fewer deaths.

To scientifically determine how many lives are saved by CAC screening, we would need an extremely large randomized controlled trial lasting for at least 6 years.

Individuals with low or intermediate risk from standard risk factors for atherosclerosis would receive a standard approach to management or would undergo CAC screening with treatment determined by calcium score.

Such trials have been proposed but to date have not been funded by the NIH thus we may not have a definite answer for a long time.

Should CAC Scans Be Covered Like Mammography?

I am very conflicted on this question.

On one hand I do believe that appropriate use of CAC scans prevents heart attacks and sudden death. How many, remains to be seen. As we saw for mammography, only large scale randomized trials will tell us for sure who will benefit and how much.

On the other hand, I can see potential for abuse, and in the wrong hands, excessive downstream invasive testing, which will minimize the benefits of early detection.

If CAC scans are covered by insurance and used widely, they could become a method for unscrupulous cardiology centers and doctors to proceed to unnecessary testing that would ultimately increase the amount of inappropriate coronary stenting.

Indeed, it is quite ironic that the major theme of The Widowmaker, that of the medical-industrial stent complex suppressing CAC scan usage, is quite illogical, for widespread, injudicious use of CAC scanning would be a boon for stent inserters and makers.

The inappropriate use of CAC scan information is limited currently because most of the doctors ordering them are primarily interested in prevention, not in generating more testing and procedures.

The other limit on its use is cost. For 99% of my patients the $125 for a CAC scan at my hospital is not a limiting factor.

On the other hand, in a less affluent population, this would be a large and limiting expense; the poor would be getting a lesser standard of care.

The cases of patients in The Widowmaker who feel like a CAC scan saved their lives are very similar to those of breast cancer patients who feel mammography saved theirs.

These patients often become passionate advocates for a specific test based on their own experience. The Widowmaker, in fact, was funded by David Bobbett, an Irish millionaire who discovered that he had an extremely high calcium score and now feels like everyone should get the test.

Bobbett is convinced that the test saved his life, but all anecdotal patient stories about CAC scans “saving their life” have to be taken with a grain of salt.

After this (far too long) discussion I have to conclude that although they share many features, CAC scans are not the mammography of the heart.

uncharacteristically verbosely yours,

-ACP

The Widowmaker Documentary: A Need For Heroes and Villains Detracts From The Truth

The documentary, The Widowmaker (available on Netflix streaming)  should definitely be watched by everyone.

It presents some great information on dying suddenly from heart attacks in an entertaining way.

It makes two important points: coronary stents don’t prevent heart attacks and coronary scans can identify advanced coronary artery disease before heart attacks happen.

I am in total agreement with these two points and have made them several times in previous posts (here and here).

The film is a work of advocacy, however, and twists the truth to prove its underlying theory: that greedy doctors and hospitals are choosing to “push” expensive coronary stents that do no good until you are having a heart attack. Also, that doctors and hospitals are also somehow suppressing the use of coronary calcium scans, which could prevent millions of heart attacks and deaths.

Creating black and white heroes and villains in documentaries makes for riveting entertainment, but often at the cost of sacrificing the truth.

Let’s look at the  villains that The Widowmaker presents.

First up is Julio Palmatz. Dr. Palmatz is a vascular radiologist who invented, along with Dr. Shatz, one of the three primary stents that ultimately gained widespread clinical usage. The Widowmaker implies that Palmatz was THE stent developer, and follows Julio as he revisits the garage in Texas where he developed prototypes for the slotted tube stent.

At this point in the movie, it would be understandable if you thought Julio was going to be one of the heroes. He seems very personable as he describes the inspiration for his stent design and points out the area in the garage where his work bench stood.

However, the documentary wants, ultimately, to portray Palmatz as greedy, unconcerned about patient welfare, and in the pocket of wealthy investors.

He has done well financially because the patent on his coronary stent was eventually sold to Johnson and Johnson for millions (and he is interviewed on the grounds of his Napa Valley vineyard).

A recent scholarly analysis of the process of the development of stents differs with this portrayal of Palmatz:

“We found that the first coronary artery stents emerged from three teams: Julio Palmaz and Richard Schatz, Cesare Gianturco and Gary Roubin, and Ulrich Sigwart. First, these individual physician-inventors saw the need for coronary artery stents in their clinical practice. In response, they developed prototypes with the support of academic medical centers leading to early validation studies. Larger companies entered afterwards with engineering support. Patents became paramount once the technology diffused. The case of coronary stents suggests that innovation policy should focus on supporting early physician-inventors at academic centers.”

Although stents ultimately have become over-utilized, they represent a tremendous invention and contribution to cardiac care.

In the setting of acute heart attacks, stents are clearly life saving and thousands of patients have had their clinical angina or claudication greatly relieved when stents are utilized appropriately for blocked coronary and peripheral arteries.

Consequently, Palmatz and many of the other interventional cardiologists who developed and performed early studies on coronary stents are widely considered heroes by the vast majority of knowledgeable cardiologists.

There is no evidence that they have colluded with industry to inappropriately promote stents or to suppress utilization of methods for early diagnosis and prevention of coronary artery disease.

The documentary then switches to characterizing the world of cardiology after stents were approved by the FDA in the early 90s.

There clearly was (and is) an irrational exuberance about stents and some of this sprang from excellent reimbursement for doing the procedures.

The focus moves to Mt. Sinai Hospital in Manhattan, and arguably the busiest interventional cardiologist in the world, Samir Sharmin.

The movie implies that Mt. Sinai was going broke until it began performing lots of catheterization and stent procedures. Sharmin who does over 1500 interventions per year and apparently earns over 3 million dollars per year is interviewed and filmed performing a stent procedure.

The average viewer likely gathers from the context of the interview with Sharmin, that he is only doing these procedures to make money.

At various points during the movie, Dr. Steven Nissen, past president of the American College of Cardiology, is interviewed and referred to as “America’s top cardiologist.”

In my opinion, Nissen has been an outstanding, independent voice of reason in the world of cardiology. During the interview, he makes the very valid points that coronary calcium scans have not been embraced for routine usage because there are no outcomes data.

At one point he says, “I don’t like medical cults” in reference to those who support more widespread coronary calcium scans.

The movie leaves the uninformed viewer thinking that Nissen is part of a cabal blocking coronary calcium scans, perhaps due to his connections with industry or an inappropriate resentment of the “calcium club” pushing the scans.

Nothing could be further from the truth. I think Nissen is one of the few prominent cardiologists who are not subject to major bias of one type or another and I strongly respect his opinions.

The movie also attempts to portray the editor of Circulation, a major cardiology journal supported by the American Heart Association as inappropriately withdrawing a paper that would have endorsed coronary calcium scanning. It’s not possible to really tell what the truth is about this withdrawal, but this is a very minor episode in the history of coronary calcium scanning.

Ultimately, The Widowmaker fails its audience in presenting the truth because it desperately wants to convince us that there is a connection between the promotion of coronary stents and the failure of coronary calcium scans to be accepted by guidelines and covered by insurance.

There is no such connection. Many interventional cardiologists are enthusiastic promoters of prevention and aggressive use of coronary calcium scans. I have seen no evidence of greedy interventionists trying to  suppress coronary scans.

In Part II of this analysis, I will take a look at the “heroes” of The Widowmaker, the inventors and promoters of coronary calcium scans, and we will see if they are truly heroic.

 

 

Moogfest, the Z-pak, the QT interval and Sudden Cardiac Death


kraftwerk
The skeptical cardiologist was planning on attending Moogfest 2014 in Asheville, North Carolina last weekend. I was going with the old friend and life coach of the skeptical cardiologist (OFLCSC) and planned on taking in electronic and synthesizer legends like Kraftwerk and Keith Emerson, riding bikes and drinking lots of craft beer. Unfortunately, a very bad upper respiratory infection took hold of me, progressing to what felt like a pneumonia (shaking chills, fever, coughing up dark, thick sputum, rattling emerging from the depths of my lungs) and I had to cancel the trip.

After processing multiple factors of risk versus benefit (not to mention the contribution to resistant bacteria), I decided to start myself on a Z-pak which is commonly utilized for community acquired pneumonia (does this mean I have a fool for a doctor?)

Azithromycin (the macrolide antibiotic in the Z-pak) , due to its broad antibiotic spectrum and perceived favorable safety profile, became one of the top 15 most prescribed drugs and the best-selling antibiotic in the United States, accounting for 55.4 million prescriptions in 2012.

The time between onset of electrical activation of the ventricles (Q) and the depolarization or reset of the ventricles (T) is called the QT interval. You can be born with a prolonged QT interval or it can become prolonged due to certain conditions. Prolonged QT intervals increase risk of sudden death
The time between onset of electrical activation of the ventricles (Q) and the depolarization or reset of the ventricles (T) is called the QT interval. You can be born with a prolonged QT interval or it can become prolonged due to certain conditions. Prolonged QT intervals increase risk of sudden death from abnormal rhythms like torsades de pointes type of ventricular tachycardia

Between 2004 to 2011, the FDA received 203 reports of azithromycin-associated QT prolongation (see graphic to the left) Torsades de Pointes (graphic) ventricular arrhythmia, or, in 65 cases, sudden cardiac death.

This prompted a review of Tennessee medicaid data which was published in 2012.

tdp
Torsades Des Pointes (fancy French word  for twisting of the points: note how the deflections seem to be oscillating slowly (somewhat like a sine wave I would have heard at Moogfest) . This is felt to be the way QT prolongation from medications like the Z-pak cause sudden death.

This study found that people taking azithromycin over the typical 5 days of therapy, had a rate of cardiovascular death 2.88 times higher than in people taking no antibiotic, and 2.49 times higher than in people taking amoxicillin. Most of the risk appeared to be those patients who had a baseline high risk of cardiovascular disease and the excess risk of death resolved after the 5 days of therapy.

As a result, the FDA added a warning to the azithromycin package insert and urged health care professionals to use caution  when prescribing it to patients known to have risk factors for drug-related arrhythmias, including those with long QT intervals, either congenitally or induced by drugs, low potassium or magnesium levels, slow heart rates or on other medications drugs used to control abnormal heart rhythms (amiodarone, sotalol and dofetilde). 

I survived my 5 day brush with a three-fold increased risk of sudden death and I really think the Z-pak substantially helped me get over the bacterial lung infection I felt I had. I knew my risk factors in detail and they were low. I was totally aware of any interacting drugs that could prolong my QT interval.

You can survive too. Make sure you definitely need the drug (i.e. you have a bacterial infection not just the common cold) and be cautious if you have any of the following

  • Family history of sudden death
  • Personal history of unexplained passing out or dizziness
  • Use of other medications that prolong QT interval (PDF)
  • Low potassium or magnesium levels (not uncommon in heart failure patients who are on water pills)
  • Severe heart disease of any kind

A complete listing is available here.

Meanwhile, Enjoy a sample of whatl I missed at Moogfest: Dorit Chrysler playing the theremin