NEJM article on HCM w/obstuction... information to KNOW

[Lisa Salberg]

Posted below is simply an abstract not the complete article. I suspect that this will create a bit of concern for some of you and some additional thought to your treatment plan may be in order. Please note that this is refering to those with gradients of 30mm or greater at rest. This may support the idea that reducing gradient is beneficial and may suggest that earlier intervention can be concidered in selected patients. forward note by Lisa

Effect of Left Ventricular Outflow Tract Obstruction on Clinical Outcome in Hypertrophic Cardiomyopathy

Martin S. Maron, M.D., Iacopo Olivotto, M.D., Sandro Betocchi, M.D., Susan A. Casey, R.N., John R. Lesser, M.D., Maria A. Losi, M.D., Franco Cecchi, M.D., and Barry J. Maron, M.D.

Cardiomyopathy/Myocarditis
Heart Failure
Related Chapters at Harrison's Online

ABSTRACT

Background The influence of left ventricular outflow tract obstruction on the clinical outcome of hypertrophic cardiomyopathy remains unresolved.

Methods We assessed the effect of outflow tract obstruction on morbidity and mortality in a large cohort of patients with hypertrophic cardiomyopathy who were followed for a mean (±SD) of 6.3±6.2 years.

Results Of the 1101 consecutive patients, 273 (25 percent) had obstruction of left ventricular outflow under basal (resting) conditions with a peak instantaneous gradient of at least 30 mm Hg. A total of 127 patients (12 percent) died of hypertrophic cardiomyopathy, and 216 surviving patients (20 percent) had severe, disabling symptoms of progressive heart failure (New York Heart Association [NYHA] functional class III or IV). The overall probability of death related to hypertrophic cardiomyopathy was significantly greater among patients with outflow tract obstruction than among those without obstruction (relative risk, 2.0; P=0.001). The risk of progression to NYHA class III or IV or death specifically from heart failure or stroke was also greater among patients with obstruction (relative risk, 4.4; P<0.001), particularly among patients 40 years of age or older (P<0.001). Age-adjusted multivariate analysis confirmed that outflow tract obstruction was independently associated with an increased risk of both death related to hypertrophic cardiomyopathy (relative risk, 1.6; P=0.02) and progression to NYHA class III or IV or death from heart failure or stroke (relative risk, 2.7; P<0.001). The likelihood of severe symptoms and death related to outflow tract obstruction did not increase as the gradient increased above the threshold of 30 mm Hg.

Conclusions In patients with hypertrophic cardiomyopathy, left ventricular outflow tract obstruction at rest is a strong, independent predictor of progression to severe symptoms of heart failure and of death.



Source Information

From the Division of Cardiology, Tufts–New England Medical Center, Boston (M.S.M.); the Regional Referral Center for Myocardial Diseases, Azienda Ospedaliera Careggi, Florence, Italy (I.O., F.C.); the Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University of Naples, Naples, Italy (S.B., M.A.L.); and the Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis (S.A.C., J.R.L., B.J.M.).

Address reprint requests to Dr. Barry Maron at the Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, 920 E. 28th St., Suite 60, Minneapolis, MN 55407, or at [email protected].

[Lisa Salberg]

Jan 22, 2003
LV outflow tract obstruction predicts death, progression to heart failure in HCM patients

Boston, MA - A new study confirms that the presence of left ventricular outflow tract obstruction, occurring in about a quarter of patients with hypertrophic cardiomyopathy (HCM), is a "strong, independent" predictor of progression to severe symptoms of heart failure and death in these patients. The report appears in the January 23, 2003 issue of the New England Journal of Medicine.[1]

Although symptoms relating to LV outflow tract obstruction are relieved by treatments aimed at reducing obstruction, the long-term significance of resting obstruction has never been described, said first author Dr Martin S Maron (Tufts-New England Medical Center, Boston).

"For the first time we've actually shown that obstruction is a marker for progression to worsening heart failure and heart failure death, which is important," Maron told heartwire.

Murmur 1 of the earliest known features of HCM
The murmur created by LV outflow tract obstruction was part of the first clinical descriptions of HCM, Maron said. In some patients with the disease, the anterior leaf of the mitral valve touches the septum, causing a dynamic outflow tract obstruction and causing a gradient between the left ventricle and the aorta. Several therapeutic interventions have been introduced to relieve the disabling symptoms of the obstruction, including a surgical procedure called ventricular septal myectomy, currently the gold-standard treatment. Newer procedures include percutaneous alcohol septal ablation and dual-chamber pacing, the researchers write.

However, what has not been completely clear is what effect having this subaortic gradient has on clinical outcome over the long term, Maron said. "The inference was that it was potentially a bad thing, because when patients were really symptomatic, we would do either surgery or ablation to help relieve that obstruction and they would feel better, but no one had actually looked at whether or not over the long haul those patients actually develop worse heart failure, worse heart failure death, or for that matter, sudden death."

To find out, Maron and colleagues (including senior author Dr Barry J Maron [Minneapolis Heart Institute Foundation, MN], Maron's father), studied 1101 consecutive HCM patients from the Minneapolis Heart Institute Foundation and 2 centers in Italy, Azienda Ospedaliera Careggi, Florence, and Federico II University of Naples.

Of these patients, 273 had obstruction of left ventricular outflow at rest, defined as a peak instantaneous gradient of at least 30 mm Hg. Patients were followed for a mean of 6.3 + 6.2 years.

Burden of risk increases over time?
Of the overall group, 127 (12%) died of HCM and 216 (20%) of surviving patients had severe, disabling symptoms of progressive heart failure, graded as NYHA classes 3 and 4.

The researchers found that the overall probability of death and the risk of progression to NYHA class 3 or 4 or death from heart failure or stroke was significantly higher among patients with outflow tract obstruction.



Risk of death or heart failure progression in HCM patients with outflow tract obstruction vs those without

Outcome
Relative risk
p

Death
2.0
0.001

Progression to NYHA class 3 or 4 or death from heart failure or stroke
4.4
<0.001




This increased risk was particularly evident among patients who were 40 years of age or older (p<0.001). "When you look on the curves, the patients who were older than 40 in class 2 did worse with obstruction than all the other subgroups, and I think that's reflective of the amount of time that they were living with obstruction," Maron said. "It takes an overall effect eventually."



Multivariate age-adjusted risk of death or heart failure progression in HCM patients with outflow tract obstruction vs those without

Outcome
Relative risk
p

Death
1.6
0.02

Progression to NYHA class 3 or 4 or death from heart failure or stroke
2.7
<0.001


To download tables as slides, click on slide logo below


Currently, the standard of care is to use major nonpharmacologic interventions to reduce outflow tract obstruction only when patients are in the later stages of heart failure and are completely refractory to medical management, Maron said. "The question is, then, is it reasonable to intervene at an earlier stage, such as perhaps late class 2, when it looks like patients are progressing despite maximal medical management?" he said. While their study obviously cannot answer this question, he added, "It could be a reasonable inference at this point, based on these data."

This information could be gleaned only from a randomized trial, perhaps of early vs later intervention, but such a trial could be difficult in this group of patients. HCM patients are often very young and symptomatic in their 30s and 40s, so follow-up of very long periods of time would be required. It would not perhaps be impossible, but "it's certainly not in the works right now," he said.

[Robert Hartwell]

Thanks Lisa, what a great article. One thing that they don't mention is the affect of an obstruction on the mitral valve. When I spoke with Dr. Lytle prior to my surgery, he told me that with each heartbeat, my mitral valve was impacting on the septal wall and could eventually lead to the need for a valve replacement.

Folks may start to consider whether they should advance their treatment from medication to something more, even though their symptoms are not very bad. Consult with your specialist!

Bob

[Tim Stewart]

HEADLINE: Disorder Deadlier Than Thought...

Copyright 2003 Newsday, Inc.

Newsday (New York, NY)

January 23, 2003 Thursday NASSAU AND SUFFOLK EDITION

SECTION: NEWS, Pg. A29

LENGTH: 482 words

HEADLINE: Disorder Deadlier Than Thought;
Study looks at heart obstruction

BYLINE: By Delthia Ricks. STAFF WRITER

BODY:

New research has ended a 50- year-old controversy over how to identify the
most serious cases of a type of heart disease best known as the No. 1 killer of
young athletes.

The disorder has a tongue twister of a name: hypertrophic cardiomyopathy, or
HCM for short, and it is the leading genetic cause of heart disease in the
United States, doctors say. The disorder affects 1 in 500 people and its
signature symptom is thickening of the heart.

The disorder often remains undetected until it has caused death, usually in a
young athlete. In older people, the disease is typified by shortness of breath,
chest pain and blackouts. An echocardiogram can spot the disease.

Doctors first described the disorder in the 1950s, noting two distinct forms,
a type characterized only by thickened muscle, and another with thickened muscle
and an obstruction in the heart's left ventricle. Since the '50s, doctors have
been divided over whether the obstructive form, which can hinder blood flow, is
a predictor of more serious disease and death.

"There was reasoning behind this," said Dr. Martin Maron, a cardiology fellow
at Tufts-New England Medical Center in Boston. "There are a lot of patients who
lived and did well despite the obstruction."

Now, in a report in today's New England Journal of Medicine, Maron and an
international team that studied 1,101 patients for more than six years concluded
that the obstructive form is a definite predictor of worsening symptoms.

Researchers studied the flow of blood through patients' hearts. For those
with the worst forms of the disease, the obstruction severely impeded blood flow
even while patients were resting.

Former defense secretary Les Aspin died at age 56 in 1995 from a stroke
linked to the disorder. In 1999, a 7-foot-tall University of Kentucky basketball
recruit collapsed and died of the disease during a high school game.

Maron said only 25 percent of people diagnosed with the disease have the
obstructive form. Currently, doctors treat the condition with several types of
medication, such as beta blockers, which reduce the heart's workload, or
implanted defibrillators. But Maron added that more aggressive treatment, such
as surgery, may be in order.

Dr. Mark Sherrid, director of the HCM program at St. Luke's- Roosevelt
Hospital Center in Manhattan, said the new study advances knowledge about the
disease.

"This is very important because it resolves a long-standing controversy as to
whether obstruction increases mortality or not. Certainly, it will make doctors
more likely to treat the obstruction."

Sherrid added that thickening of the heart muscle is not unusual in athletes.
However, those with the trait can experience unusual thickening. "A small degree
of thickening, up to 14 millimeters, is normal in athletes... " Sherrid said.
"The thickening that occurs in HCM is ... from say, 15 to 40 millimeters."

LOAD-DATE: January 23, 2003

[Dee]

how are classes defined?

This article mentions 4 classes - I was wondering how these "classes" are defined?

Forgive me if it was mentioned in the article and I just missed it - my eyes and brain start to glaze over when I'm reading this stuff and it's a bit of a struggle to get thru it!

[Lisa Salberg]

Heart patients are classified as "New York Heart Class" 1-2-3-4
1 = someone who has no symptoms (walk up and down stairs fine)
2= mild symptoms (gets a little winded)
3= more sever symptoms (has a hard time walking up stairs)
4= extremely sever symptoms (what me walk up stairs - not)

That is not the medical book definition - but I think you get the picture.

Lisa

[Dee]

Thanx!

Thank you Lisa! You ROCK! :P

[Reenie]

Lisa,

Here's one you might have to struggle to explain to me:
You know my husband was first diagnosed in Japan with their test, their parameters, and then translated into English. The initial translated report's cover sheet said IHSS, Severe, Maroon, Type III. Do you have any idea what that meant, or was it maybe something that meant something to the Japanese that doesn't mean diddly to us?

Reenie

[Lisa Salberg]

I remember you mentioned that before - No I have no idea - its Japanese to me

lisa

[Reenie]

Thanks. I couldn't remember if I had asked before or not. Oh, well. Guess I wasn't meant to know that one!

Reenie

[Janis Grant]

Article on hocm

Lisa,
You really do rock! Great info---when do you have time for yourself.
You are right knowledge is power!!! Thanks for all you do for us! I am beginning to find my way around the new sight. Takes a little longer for this old folk.

[Lisa Salberg]

Janis... thanks! I find time for me... in many ways others would not think is "me" time....
I do find so much personal happiness in finding all of you finding each other, it is not work it is so much more.
I will be taking up a few new interests in the coming years to "clear" my head of my heart a little. I think much of that will be close to home and "in my genes".. UFF DA! a bit cryptic eh
Lisa

[Robert Hartwell]

Lisa,

As I re-read this information, I am now wondering....

Did the study done by Dr. Maron look at HOCM patients who continued to live with an outflow trac obstruction and gradient, or does this group also include patients whos obstruction was removed and gradient lowered?

Bob Hartwell

[mtlieb]

Hi Bob,

That worried me as well, and i asked <edit doctor's name> that exact question yesterday when i spoke to him on the phone. As i understand it, the study group did include patients who had received treatment for their obstruction, as well as those who had not, but in all cases the patient's gradient remained above 30mm, and eventually progressed as noted in the study. He told me that if my medication was successful in relaxing my obstruction and the gradient was reduced, that those statistics would no longer apply to me.

I was also very interested in knowing what the mean age of death was within that group but did not get an answer on that one. LOL. Hey, if it eventually does kill me, i'd at least like to have a ballpark figure

I have to admit the article really threw me for a loop when i read it. None of my doctors or specialists have ever told me that there were specific health risks associated with having a high gradient due to obstruction, even when asked directly. It's been my understanding that my high gradient was more of a nuisance than a real health threat.

Jim

[Sarah]

gradient

So the moral of the story is, get your gradient down and keep it there. And as long as your gradient is under 30 (regardless of how it got there), then you can breath a little easier.

Jim, statistics are statistics--not people! Just because the average age of morality is 50 or 60 or whatever, it _doesn't_ mean that when you hit that age your heart is going to go off like a kitchen timer. I think it is counter-productive (and wrong) to think that you only have X-number of years according to 1 study about 1 factor. The reality is that YOU could beat that number by a long, long time or you could have a stroke tomorrow. You just never know.

My two cents about mortality. No one can tell you when you are going to go.

S