Sudden Cardiac Death in Young Athletes

Editor’s Note:  This post originally appeared on the blog of Dr. Howard J. Luks. Dr. Luks  wrote this blog entry in collaboration with HCM expert Dr. Srihari S. Naidu of New York’s Westchester Medical Center. You can find the original post here.  You can find both Dr. Luks and Dr. Naidu on Twitter @hjluks and @SrihariNaiduMD.

Sudden cardiac death in young athletes continues with alarming frequency.  The most common cause of sudden death in the young athlete is hypertrophic cardiomyopathy or HCM.  Simply put, HCM means the heart muscle is bigger.  Many of us believe that bigger muscle means stronger muscle.  That is not always the case with the heart.  The heart is a mechanical pump with a complex arrangement of chambers which store the blood. How that pump works is controlled by a very complex electrical system.  Hypertrophic cardiomyopathy can interfere with one or both of these critical functions of the heart and lead to sudden cardiac death.

This weekend we witnessed an athlete collapse in the middle of a basketball  game.  After playing a good portion of the first half, Tyvoris Solomon was on the bench and suddenly collapsed.  One person began fanning him, and the coach knelt down in prayer, luckily, others began chest compressions.   Mr Solomon’s heart was restarted and he was brought to a local hospital for further evaluation.

How does HCM lead to death in athletes?

Sudden cardiac arrest usually is due to extremely fast heart rates. This is called an arrhythmia.  An arrhythmia can occur because the electrical wiring in the heart is affected by the excessive muscle growth in HCM patients.  The most lethal forms of abnormal heart beating is coming from the bottom chambers of the heart. It is called ventricular tachycardia or ventricular fibrillation.  In essence, the heart is going too fast to actually pull blood in and then move blood forward.  The body, getting no blood, begins to shut down, starting with the brain, which is why athletes collapse.  If not addressed quickly, our organs begin to die one by one, in a matter of minutes.

What is the cause of sudden death in athletes?

The majority of cases of sudden death in athletes are due to a heart muscle condition called hypertrophic cardiomyopathy, where the heart muscle is too thick.  Despite thickening, the heart can function quite normally for many years.  This explains why many of these kids are high performance athletes. HCM is usually an inherited disorder.  It is estimated to affect 1 in 500 people.  Not all athletes who have HCM will die because of it.  There are varying degrees of severity.

What are the symptoms of HCM?

Not all athletes with HCM will first present with sudden death.  Athletes of any age who complain of shortness of breath, lightheadedness, fainting or exercise intolerance should be evaluated by a cardiologist.  One or many of these signs might be present in athletes who suffer from HCM.  A heart suffering from HCM is very irritable… that means that its electrical system prone to develop these fast heart rates, often out of the blue but usually during or right after heavy exercise.

Can we screen for HCM?

Yes.  Any athlete with a family member who died at a young age, possible due to sports should be tested for HCM.  There are genetic screening tools as well as other tests that can be performed.  Not everyone who carries the genes in their DNA will develop HCM.  That ‘s why it is important to see a Cardiologist if you are concerned.  They will perform a physical exam, EKG and possible and ECHO.  A cardiac echo is an ultrasound that shows the heart. It can show you if part of the wall of the ventricles of heart are enlarged.

What you can do immediately after an athlete collapses

Proper training is critical. Sudden death is common enough that every school should have a protocol in place to deal with these situations.  Athletic Trainers are often very well versed in treating athletes who collapse on the court.  Every school must have a charged, and readily accessible AED or Automatic Electrical Defibrillator.   These devices will access the athletes heart rhythm and deliver the necessary shock to restart the heart.  Every Athletic Trainer should know precisely where their AED is when the games begin.

If you witness an athlete collapse, you should immediately assess their pulse. If absent you should immediately start CPR.  Every coach and parent of an athlete should have CPR training.  Do not stop CPR until personnel with an AED arrive on the scene.

Other causes of sudden cardiac death in athletes

Other causes include other types of heart muscle problems that don’t involve thickening. Generally these diseases involve inflammation or diffuse weakness of the heart muscle, called dilated cardiomyopathies.  Some of these are new problems due to a viral illness, while others may have existed for years but only now are causing symptoms.  In addition to these, there might be abnormal electrical circuits in the heart present at birth, abnormal heart arteries which could get compressed during exercise, and sudden traumatic impacts to the chest – the latter a more obvious cause to the spectator watching the action.

Future strategies to decrease risk of sudden death in our athletes

To prevent some of these arrests, some countries have put forth more aggressive screening programs including a 12-lead electrocardiogram (EKG) or even an ultrasound (echocardiogram), before each playing season.  These would pick up hypertrophic cardiomyopathy in 90% of cases, and probably most cases of the dilated cardiomyopathy and some of the electrical problems.  It’s not perfect, but it’s a start.  While the American Heart Association does not advocate for these screening programs, largely due to cost analyses, inconvenience, or that it’s hard to prove they work, they still make sense.

Since hypertrophic cardiomyopathy is the majority cause, we need to do a better job of raising awareness about this disease, find the people at risk for sudden cardiac arrest, during athletics or otherwise, and get them to centers of excellence for this disease.  Dr. Srihari S. Naidu runs the HCM program at Westchester Medical Center (WMC).   WMC serves the New York and tri-state area, and beyond, and is committed both raising awareness of HCM, how it impacts people who may not even know they have it, and how to treat it before it becomes a problem.

Dr Naidu’s words are worth noting.

“It’s time we took control, so we are not shocked and bewildered next time (an athlete collapses) and instead (we) know exactly what we’re dealing with and what to do.”

This article was written with the assistance of Dr. Srihari S. Naidu.  He is one of the top experts in the field of HCM in athletes and I thank him for his valuable contributions.

HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT, PART IV

Editor’s Note:  This is the 4th of 4 blog entries which summarizes the presentations given at the recent International HCM Summit VI in Boston.  The presenter and their hospital affiliation are noted below, along with the topic of their presentation.  When possible, you may access the presenters’ slides via hyperlink by clicking on the name. (Note that not all presenters made their slides available).

To see Part I of this series of highlights from the HCM Summit VI, click here, to see Part II of this series click here, and to see part III of this series. click here.

Dr. Martin Maron, Tufts Medical Center, Boston, MA – A New Drug For Obstructive HCM

  • Mavacamten, formerly known as MYK-461, is being tested as a treatment for heart failure symptoms in HCM. It works by decreasing the power of the heart’s contraction. On average, both ejection fraction and left ventricular outflow tract gradient decreased by 15% in the recently completed Stage II trial.
  • Not all patients who took the drug showed improvement in symptoms and functional capacity.  The percentage of patients showing clinical improvement on mavacamten was similar to that seen with disopyramide.
  • Currently it is unclear what the long term effects of the drug will be.  This may become clearer after the upcoming Stage III trials.

Dr. Iacopo Olivotto, Careggi University Hospital, Florence, Italy spoke about the sudden termination of the clinical trial of the Gilead drug eleclazine.  A link to the HCMBeat story about this can be found here. 

Dr. Steven Heitner, Oregon Health & Science University, Portland, OR spoke about gene editing in HCM and described the recent work done with CRISPR at his institution.  A link to the HCMBeat story about this research can be found here.

Dr. Benjamin Levine, Southwestern Medical Center, Dallas, TX spoke about exercise in HCM. While the risk of sudden death in young athletes may have suggested that a more sedentary lifestyle was appropriate for HCM patients, the recent RESET-HCM trial has challenged this, finding that moderate exercise is safe for patients with HCM.  (Click here for a HCMBeat interview with the principal investigators of this study, Drs. Sara Saberi and Sharlene Day).

Dr. Levine also mentioned that high-intensity interval training (HIIT) in animal models of HCM show that HIIT may be protective against myocardial disarray.

Dr. Euan Ashley, Stanford University Medical Center, Palo Alto, CA spoke about the potential ways that personalized medicine might impact HCM care in the future.  Genetic mutations may influence the tendency toward arrhythmia, age of diagnosis, and exercise capacity.  New technologies like photoplethysmography which detects blood volume changes may provide data which can be helpful in personalizing treatments.

THIS CONCLUDES THE SUMMARIES OF THE PRESENTATIONS OF THE 2017 HCM SUMMIT.  To see Part I of this series of highlights from the HCM Summit VI, click here, to see Part II of this series click here, and to see part III of this series. click here.

 

HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT VI, PART III

**Because so much HCM information was presented at the Summit, this is the third of multiple blog entries.  Stay tuned to HCMBeat for more highlights from the HCM Summit.  To see Part I of this series of highlights from the HCM Summit VI, click here and to see Part II of this series click here.**

The symposium was organized by long time HCM expert Dr. Barry Maron and his son, Dr. Martin Maron.  Both Marons are now affiliated with Tufts Medical Center’s Hypertrophic Cardiomyopathy Center.

What follows are summaries from selected talks presented at the meeting.  The presenter and their hospital affiliation are noted below, along with the topic of their presentation.  When possible, you may access the presenters’ slides via hyperlink by clicking on the name. (Note that not all presenters made their slides available).

Continue reading “HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT VI, PART III”

Exercise Testing Important for HCM Patients

According to a recent study by doctors at Tufts HCM Center in collaboration with colleagues in Italy, exercise testing is an invaluable tool in the assessment of hypertrophic cardiomyopathy patients.

In particular, two types of exercise testing are most valuable for HCM patients:

  • Exercise Echocardiogram:  These tests are valuable in determining whether a patient has obstruction.  It provides a physiological way to measure whether or not a patient has an obstructed left ventricular outflow tract and hence, may potentially be in need of an invasive procedure to treat the obstruction.  According to the article, approximately 1/3 of HCM patients have latent obstruction which may only be seen during or after exercise.  This obstruction is not always apparent from their resting echocardiogram.

and

  • Cardiopulmonary Exercise Testing:  These tests help determine functional capacity and provide a quantifiable indicator of heart failure symptoms.  This test  can identify patients in need of more aggressive treatment options, or who are potentially in need of transplant.  A particularly valuable piece of data from this test is the “VO2 max” score, which is a measure of the maximum rate of oxygen consumption during exercise which reflects the cardiorespiratory fitness level of a person.

*Editor’s note – Exercise testing was particularly informative and important in my own HCM treatment.  It was only after my doctors performed an exercise echo that the extent of my obstruction became apparent.  The symptoms I had been suffering appeared to be out of proportion to what was visualized on my resting echo.  The exercise echo helped my doctors understand the cause of my symptoms which made the next step, in my case a myectomy, much clearer.

You can read my full story here .

 

 

HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT VI, PART I

**Because so much HCM information was presented at the Summit, this will be the first of multiple blog entries.  Stay tuned to HCMBeat for more highlights from the HCM Summit.  You will find Part II of this series by clicking here.**

The 6th International HCM Summit was held October 27, 28 and 29th in Boston, Massachusetts.  This symposium brings together HCM professionals from around the world who are there to learn about and discuss the latest developments in the treatment of HCM.

The symposium was organized by long time HCM expert Dr. Barry Maron and his son, Dr. Martin Maron.  Both Marons are now affiliated with Tufts Medical Center’s Hypertrophic Cardiomyopathy Center.

What follows are summaries from selected talks presented at the meeting.  The presenter and their hospital affiliation are noted below, along with the topic of their presentation.  When possible, you may access the presenters’ slides via hyperlink by clicking on the name. (Note that not all presenters made their slides available).

Continue reading “HIGHLIGHTS FROM THE INTERNATIONAL HCM SUMMIT VI, PART I”

More is Needed for Women With HCM

A recent study published in the European Heart Journal by doctors from the Mayo Clinic showed that women with hypertrophic cardiomyopathy (HCM) have a statistically reduced rate of survival as compared to men with HCM.

Continue reading “More is Needed for Women With HCM”

A Risk Calculator for Sudden Death -Results of HCM-EVIDENCE Study

The HCM Risk–SCD Score

In 2014, the European Society of Cardiology (ESC) introduced a numerical predictor (the “HCM Risk–SCD score”) to assist physicians in identifying those patients at highest risk for sudden cardiac death who would benefit from the implantation of a prophylactic implantable cardioverter-defibrillator.

Using an algorithm generated by the answers to a series of questions, the tool estimates the 5-year risk of sudden cardiac arrest for any particular patient.  You can find the tool online here.

Continue reading “A Risk Calculator for Sudden Death -Results of HCM-EVIDENCE Study”

Multiple Mutations in HCM

A recent paper by researchers in Australia, published this week in Circulation: Cardiovascular Genetics, found more than one rare HCM gene in 4% of patients in a 758 patient sample group.

The researchers found that those patients with multiple rare HCM genes tended to present with HCM at a younger age, were more likely to experience cardiac arrest or death from other causes, and were more likely to require a heart transplant.

In general, few patients have multiples of mutations commonly associated with HCM.  See this Canadian study from April of this year which found that multiple mutations were less prevalent and harmful than previously thought.

Encouraging Results for MyoKardia HCM Drug

MyoKardia’s stock prices jumped today after their recent Stage II trial of the experimental drug mavacamten (formally known as MYK-461)  demonstrated a statistically significant reduction to left ventricular outflow tract gradients as well as improvement to aerobic capacity in patients with obstructive hypertrophic cardiomyopathy.  

Of the 10 patients who completed the study, 8 saw their gradient reduced to normal levels after 12 weeks on the drug.  The study also showed improvements in both peak oxygen consumption (peak VO2) and New York Heart Association classifications:  7 patients moved up one NYHA class while 2 patients improved by two classes.

The drug seemed to have mild to moderate side effects, though one patient was forced to drop out of the trial due to a recurrence of atrial fibrillation which necessitated discontinuation of mavacamten and a return to anti-arrythmic drugs which had been discontinued due to participation in the trial.

MyoKardia hopes to enroll between 200 and 250 patients in its next phase trial (Explorer HCM) which it plans to begin before the end of 2017.

MyoKardia also plans a clinical trial of mavacamten in non-obstructive HCM patients in the second half of 2017.

For more information on MyoKardia and  recent drugs being developed for HCM read these past blog entries:

MyoKardia HCM Drug Has Success in Cats

End of the Road for Eleclazine and Liberty HCM Study

HCM Drug Trial Advances to Next Round

Drug for Non-Obstructive HCM Moves Along

CRISPR Eliminates HCM Gene !

Scientists, in a follow up to three earlier, less successful, Chinese experiments, have for the first time used a recently developed gene editing process known as “CRISPR” to remove a genetic defect from a human embryo.  The specific defect that the scientists targeted was a mutation in MYBPC3, a common genetic cause of hypertrophic cardiomyopathy (HCM).

What Happened in the Study?

The study authors consisted of a multi-national team of geneticists, cardiologists, fertility experts and embryologists.  Led by Dr. Shoukhrat Mitalipov of Oregon Health Sciences University, in collaboration with researchers at the Salk Institute in La Jolla, CA, China and South Korea, the researchers were able to largely remove the HCM gene MYBPC3 from very early stage human embryos.

Their research involved using eggs from 12 healthy female donors, and sperm from a male HCM patient with the MYBPC3 gene.  When gene-editing components were introduced to the egg along with the sperm, prior to fertilization of the egg, approximately 3/4 of the embryos repaired themselves using the DNA blueprint provided by the normal, non-mutated copy of the gene from the unaffected female.  This was somewhat surprising to researchers, who had theorized that cells would replicate using a blueprint from the repaired paternal gene – not the healthy gene of the mother.

Ultimately, genes were corrected in 42 of 58 embryos, constituting 72.4% of the total, a higher proportion than expected, and far more than any correction shown in previous experiments.

Implications for the Future

This technique is still far from general usage and will require further study and refinement.  And, currently it is not legal in the United States since the Food & Drug Administration currently prohibits medical gene editing which would impact future generations.

However, it would be possible for this technique to be used alongside current technology to assist families with genetic diseases like HCM.  If used in conjunction with pre-implantation genetic testing and in-vitro fertilization (PGD), the technique could repair the large proportion of embryos (roughly 50%) which must be discarded due to genetic defectiveness.

While there are critics who say that this technology will lead to “designer babies” and that it creates troubling ethical issues for society, most HCM patients believe that it provides a ray of hope, so that hopefully one day, in the not-too-distant-future, our children and grandchildren will be free of the affliction that has permeated our lives, as well as the lives of our siblings, our parents, our aunts and uncles, our cousins, our grandparents, and our great-grandparents.

Story Links:

As this story was reported by all major news sources, links to many of the articles can be found below.

Nature

The Atlantic

New York Times

Washington Post.

NPR

LA Times

Los Angeles Times – Q&A video clip with lead study author Shourkhrat Mitalipov

The Guardian

USA Today

MIT Technology Review

Gizmodo

Boston Herald

LA Times article regarding ethics -response to first article

NOTE THAT APPROXIMATELY A MONTH AFTER THE PUBLICATION OF THIS ARTICLE, THE RESULTS HAVE BEEN CALLED INTO QUESTION BY OTHER SCIENTISTS.

See this article in MIT Technology Review, this article in Science Magazinethis article in Nature, and this article in The Scientist, all of which cite this article in BioRxiv which poses alternative theories for the results claimed by the original paper.