COMMENTARY

Mandrola's Top 10 Cardiology Stories of 2017

John Mandrola, MD

Disclosures

December 20, 2017

2017 might be called the year of the medical reversal.

1. ORBITA: Stent vs Sham

A medical reversal occurs when a superior clinical trial contradicts current practice. Reversals serve two purposes: one is progress, but the other more vital effect is to tamp down hubris.

Hubris has no greater foe than the sham control. Before Dr Rasha Al-Lamee (Imperial College London, UK) presented findings of the ORBITA trial,[1] PCI in patients with stable coronary artery disease had been relegated to angina relief alone. The 2007 COURAGE trial[2]—and its substudies—had shown that stenting coronary lesions did not reduce MI or prolong life.

In patients with single-vessel disease, ORBITA found that fixing lesions (that few operators would walk away from) did not significantly improve exercise capacity or angina symptoms compared with a sham procedure. These findings sparked disbelief among the interventionalists, who swarmed Twitter with critical appraisal. In a letter in Eurointervention, Drs Al-Lamee and Francis addressed the major criticisms, including the ethical responsibility to do sham controls.[3] ORBITA may be the biggest cardiology story in a decade.

2. Failure to Accept the BVS Failure

The fall of the bioabsorbable stent made last year's top-10 list. I'm adding it to this year's list as well for two reasons: Not only did bioresorbable vascular scaffold (BVS) look worse over time (the opposite of its promise), but also because of the failure of some key opinion leaders to let it go and admit error. It should not be lost in this lesson that thousands of humans received a clearly inferior device.

At the ACC meeting in the spring, 2-year results of the ABSORB-3 trials reported a 3.1% higher rate of target lesion failure in in the BVS group vs a regular drug-eluting stent (Xience, Abbott Vascular). That news brought a warning letter from the FDA. No matter: Dr Stephen G Ellis (Cleveland Clinic, OH) said patients in the Xience arm did "somewhat better." And Dr Roxanna Mehran (Mt Sinai, New York) was "somewhat comforted" that event rates were not extremely high in the BVS arm.

Two months later, Dutch investigators, publishing in the New England Journal of Medicine, reported that the most feared PCI complication—stent thrombosis—was nearly fourfold higher with BVS vs metallic stents.[4] At the TCT meeting, 1-month after Abbott halted sales of BVS, Dr Ellis presented the 3-year results of ABSORB-3, and again BVS performed poorly against Xience, with a 3% higher rate of target lesion failure and a threefold higher rate of device thrombosis. [5]

Instead of saying BVS didn't work, and that we and the FDA erred, ABSORB investigators published a quasi meta-analysis of BVS trials looking at operator technique[6] and an editorial in the field's most prominent journal was titled "Can the vanishing stent reappear?"[7]

Trust is hard won and easily lost.

3. The Great Fat Debate

Speaking of trust, earlier this year, a motivated middle-aged man riddled with atherosclerosis asked me a simple question: "Doc, what's the absolutely best diet? I will do it. Just tell me."

And the crazy thing is that I, an experienced cardiologist, have no idea.

Should I give him the advice prescribed from the 2017 Presidential Advisory From the American Heart Association, which reiterated the danger of saturated fat?[8] Or, should I proclaim allegiance to Dr Salim Yusuf, senior author of the massive PURE study, which observed (key verb, as this was an observational study) the association between fat intake, even saturated fat, and lower cardiovascular events and mortality?[9]

The low-fat camp can cite Dean Ornish's work[10] and Dr Esselstyn's anecdotes of CAD reversal.[11] The fat-friendly camp can cite the PREDIMED randomized controlled trial[12] and The Basement Tapes from Malcolm Gladwell's Revisionist History podcast. This 2017 episode tells the poignant story of how missing files from the Minnesota Coronary Experiment (MCE) finally got published.[13] Conducted from 1968 to 1973 in institutionalized adults, the double-blind MCE study found that replacement of saturated fat with vegetable oil rich in linoleic acid led to reduced serum cholesterol levels but higher rates of death. Pause on the magnitude of that reversal for a moment.

4. Renal Protection Not Protective

Two randomized controlled trials published this year reversed belief in three practices thought to protect against contrast-induced nephropathy.

In AMACING, preprocedure IV saline proved noninferior to no treatment in high-risk patients (estimated glomerular filtration rate [eGFR] 30–59 mL per min/1.73 m2).[14] Symptomatic heart failure occurred in 4% of the saline group vs none in the no-treatment group.

In PRESERVE, neither sodium bicarbonate nor oral acetylcysteine proved beneficial in a slightly higher-risk group of patients (eGFR 15-45 mL per min/1.73 m2).[15]

Less sure seems like more when it comes to prevention of contrast nephropathy.

5. Clot Sucking Flops in Veins and Arteries

The benefits of debulking thrombus by mechanical means once again did not stand up to scrutiny in a clinical trial. The ATTRACT trial found that adding pharmacomechanical catheter-directed thrombolysis to anticoagulation did not reduce the risk of the postthrombotic syndrome but did result in a higher risk of major bleeding in patients being treated for acute proximal deep venous thrombosis.[16]

These findings mirror the results of TASTE[17] and TOTAL[18] and a meta-analysis[19] that found that routine thrombus aspiration during primary PCI did not improve clinical outcomes in patients with STEMI.

Clot sucking makes the top-10 because I still hear colleagues say they do it—because they "know it works."

6. Opioid Epidemic Reaches Cardiology

It's sad to have to include this topic in a cardiology recap.

The organ reserve and resilience of young people stands in stark contrast to the elderly.

This is not the case for the young people ravaged by opioids. Cardiologists and cardiac surgeons now routinely see young people who simply cannot be fixed.[20] Aortic abscesses, septic emboli to the brain and kidney, and overdoses after discharge are all common causes of death of these young people.

It's not unusual to see people return for their second or third heart surgeries. I've had to learn new pacing techniques because of the rising tide of endocarditis.

One of our surgeons recently expressed something you almost never hear from a surgeon: hopelessness. "John, I don't think I've saved even one of these youngsters. They all go back to drugs. I think they all die."

7. Hypertension Guidelines

At 283 pages and 367 references, the new blood-pressure guideline document[21] garnered controversy because it lowered the threshold for diagnosing hypertension (130/80 mm Hg) and greatly expanded the number of people with a labeled disease.[22] Also controversial was its endorsement of a cardiovascular risk-based decision algorithm. Most experts agreed with the emphasis on accurate blood-pressure measurement, call to consider ambulatory blood-pressure readings, and strong nod to lifestyle measures.

Nine other professional organizations endorsed the AHA/ACC hypertension guidelines. But not the American Academy of Family Physicians. In a press release, the AAFP gave multiple reasons for dissent. Among them: the majority of recommendations were not based on a systematic review, assessments of individual studies were not provided, and the authors gave too much weight to the SPRINT trial.[23]

We should be thankful for the AAFP's skepticism. Indeed, high blood pressure is a serious risk factor, but labeling almost half the population with a disease warrants caution. The influential Stanford epidemiologist John Ioannidis recently wrote in JAMA that "guidelines are typically the final step to justify illness-by-committee and treatment overuse." [24]

The guideline was published in November 2017; it will take most of 2018 to absorb its implications. I already think a lot more about ideal blood pressure and its measurement. Thinking more seems like a positive side effect of the document.

8. Inflammation and Heart Disease

We think inflammation plays a pivotal role in atherosclerosis. What's been missing in this theory is an anti-inflammatory treatment that reduces heart disease.

Enter canakinumab, a human monoclonal antibody against interleukin-1β, which is already FDA-approved for its anti-inflammatory effects in rare immune disorders.

The CANTOS trial tested three doses of canakinumab in patients optimally treated with statins who had previous MI and a high-sensitivity C-reactive protein levels ≥2 mg/L.[25] And it worked. Canakinumab reduced inflammation (lowered hs-CRP) and the 150-mg dose (medium dose) resulted in a statistically significant reduction in a composite end point of nonfatal MI, nonfatal stroke, and cardiovascular death, albeit with a statistically higher rate of fatal infections.

I see two frames for CANTOS. Scientifically, the potential discovery of an inflammatory target for atherosclerosis, one that is independent of LDL-lowering, could be huge. Future docs may look back on this trial as the beginning of a new chapter. Clinically, however, the drug's modest benefit in nonfatal events, presumed high cost, and higher rate of fatal infections will impede its clinical utility. Canakinumab's most promising effect may be as an anticancer drug.[26]

9. MRI Safety and Cardiac Devices

Few things aggravate me more than nonsense inhibiting good patient care. That we withhold MRI from patients with cardiac devices under the guise of safety is utter nonsense. This year, two publications back me up on this.

First was the publication of the MagnaSafe Registry in the New England Journal of Medicine. This was a prospective multicenter study involving more than 1200 patients with non–MRI-conditional pacemakers or ICDs who underwent approximately 1500 scans. Using a standardized protocol, no deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI.[27]

The second publication lending credence to the safety of MRI scanning of essentially any patient with any cardiac device was the HRS expert consensus statement.[28] Yes, I was an author on this document, and yes, it's always good to be skeptical of expert statements. But I challenge you to review the references and recommendations in this document and then make an argument that an appropriate MR scan done under careful monitoring does not meet any reasonable definition of safe.

10. Noninvasive Catheter Ablation

Destroying myocardium in a controlled way is the core idea of catheter ablation. This process now involves human operators invading the body with catheters—for both mapping and ablation.

Investigators from Washington University in Saint Louis reported the first series of noninvasive mapping combined with external radiation to reduce ventricular tachycardia burden.[29] The procedure—which successfully lessened VT—averaged 14 minutes, required no sedation, and resulted in no obvious complications. This work builds on preclinical work in animal models from a Mayo Clinic group.[30]

I concede that it's hard to make a case report of five patients a top story of the year. But so much of the progress in cardiology and electrophysiology in recent years has been painfully incremental. If this technology pans out it could usher in a new era.

Readers, please feel free to disagree and suggest your ideas for top stories. For example, maybe you thought a $14,000/year drug that required a trial of more than 27,000 patients to show a 1.5% reduction in nonfatal events should have been included😉.[31]

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