Sudden Cardiac Death in Young People: More Answers

When tragedy strikes, physicians are often asked to answer two questions.  The first is the how question. How did this happen? Long illnesses provide time for patients and family members alike to come to terms with a diagnosis and prognosis. Not always, and not easily, but the time is there.  In the case of sudden cardiac death in a young person, there is no time. Sudden cardiac death is a condition that feels out of place in 2016. That a healthy person can be alive and then, simply, not, feels wrong to modern sensibilities. Nevertheless, the incidence of sudden cardiac death, about 1 per 100,000 young people per year is similar across multiple countries and cultures. Now a manuscript appearing in the New England Journal of Medicine attempts to shed light on how sudden cardiac death can happen. For the video version of this post, click here.

The researchers examined literally every case of sudden cardiac death occurring in individuals less than age 35 in Australia and New Zealand from 2010 to 2012 in a prospective fashion. With each of the 490 cases, they examined autopsy and toxicology reports to determine how the death occurred. While 60% of the cases were explainable by conditions like coronary artery disease and hypertrophic cardiomyopathy, a disturbing 40% had no revealing findings.

So they expanded the search, in a subset of that 40%, the researchers performed advanced genetic sequencing to look for gene mutations that could predispose to sudden death. They found mutations of that type in 27% of the otherwise unexplained cases. While the gap of understanding was narrowed a bit, the how question remained unanswered for many individuals.

Now I should mention that identifying disease-causing mutations is not as easy as it sounds. Most of the mutations identified were classified as “probably pathogenic”. Basically, that means that the mutations are predicted to do harmful things to the protein they affect, but we don’t know for sure at this time.

To take the analysis a step farther, the researchers examined family members of the deceased to screen for the presence of heritable cardiac conditions. In 12 of 91 families screened, such a condition – like long QT syndrome – was found.

So what we have here is a great example of a well-conducted, methodical, and meticulous study that has moved us incrementally towards greater understanding. For some of the families who suddenly lost a loved one – the answer to “how did this happen” is now clear.

Of course that’s only one of the two questions we get asked.  The other is “why did this happen”? And that’s a question that no methodology, no matter how advanced, can answer.

Statins to prevent acute kidney injury after cardiac surgery

Statins, is there anything they can’t do? These agents, granted blockbuster status more than 20 years ago, are potent weapons in our fight against cardiovascular disease. But beyond their cholesterol-lowering effects, we’ve seen studies where statins act as anti-inflammatories, improve immune function and even stave off dementia.  Could the wonder-drugs prevent acute kidney injury, a dreaded complication after cardiac surgery, associated with more than a three-fold increase in mortality?

For the video version of this post, click here.

Full disclosure: I research acute kidney injury, or AKI. So welcome to my world, statins – a world where positive clinical trials are as rare as an epidemiologist at a Mr. Personality contest.

The trial, out of Vanderbilt university hospital appeared in JAMA and enrolled 617 individuals undergoing cardiac surgery. The treatment group got 80mg of atorvastatin prior to surgery, and 40mgs a day after that. The placebo group got, well, placebo. As you might imagine, the majority of patients (400) were already taking a statin.  In that case, if you were randomized to placebo, you only got placebo for the day of surgery and the day after. After that, you were back on your home statin dose.

And to boil the results down to a word: nothing. The rate of AKI was 21% in the statin arm and 20% in the placebo arm. Looking at secondary outcomes, there were no differences in rates of death, dialysis, delirium, stroke, or stay in the ICU.

This might be expected in the group that was already on statins – after all, skipping two days of the drug might not be enough to make a real difference. But if we look at the statin-naïve group, the rate of AKI was 22% in the statin group and 13% in the placebo group. This was not statistically significant but the trend here is clearly in the wrong direction. In fact, if we look at absolute creatinine change –where higher levels are worse- those on the statin had a small, but statistically significant increase in creatinine compared to those on placebo.

But take these numbers with a grain of salt. The data safety and monitoring board forced the study authors to stop recruitment of statin-naïve patients about 2/3rds of the way through the study. They did this because they saw a signal of harm from statins in that group. So the fact that we see harm may be biased by the DSMBs choice to stop that part of the study early.

Now, would I have stopped the study if I were on the DSMB?  Probably. The odds that continuing to recruit would show a benefit of statin were really low, and you don’t want to expose patients to potential harm. But despite that, we can’t accept the results of an early-termination arm of a trial with the same gusto that we would had the trial continued to completion.  In short, the jury is still out as to whether statin use is actually harmful in terms of AKI. But I can say for now I’m pretty convinced it ain’t helping anybody.