Distinctive Dozen: 12 Developments from 2016 Likely to Reshape Cardiovascular Practice

Experts weigh in on key advancements from the past year

The past year saw more than a few advancements and other developments that will leave a lasting mark on cardiovascular practice.

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Leaders of Cleveland Clinic’s Miller Family Heart & Vascular Institute identified a dozen of the most significant developments of 2016, with a focus on those where Cleveland Clinic staff can comment from direct involvement in the advancement itself. Here’s to an equally dynamic 2017!

Growing recognition of the heart benefits of newer diabetes drugs

In December 2016, the FDA approved the SGLT2 inhibitor empagliflozin for reducing the risk of cardiovascular death in adults with type 2 diabetes and cardiovascular disease on the basis of the EMPA-REG OUTCOME trial. In July, the LEADER study showed the GLP-1 analogue liraglutide to significantly reduce rates of cardiovascular death and nonfatal MI and stroke relative to placebo among patients with type 2 diabetes. These developments exceeded the expectations of those who called on the FDA a decade ago to conduct cardiovascular outcome trials for new diabetes drugs. “We hoped these drugs would lower blood sugar and do no harm, but also reduce cardiovascular events,” says Cleveland Clinic’s Steven Nissen, MD, who led the call for outcome trials. “Our dream came true. Both drugs lower cardiovascular morbidity and mortality. In the wake of these studies, cardiologists should be talking to endocrinologists about drug choice for diabetic patients with cardiovascular disease.” For more, see this post.

TAVR expands its reach to lower-risk populations

August saw the FDA approve two valves for use in transcatheter aortic valve replacement (TAVR) among a sizable new group of patients — those at intermediate surgical risk. Expansion of the TAVR indication beyond just high-risk surgical patients came on the heels of the final two-year report out of the PARTNER 2A randomized trial finding TAVR at least as safe and effective as surgical AVR among 2,032 patients at intermediate risk of surgical complications. “It’s important to note that PARTNER 2A was a multicenter trial and that individual high-volume centers have surgical success rates that compare very well with TAVR success rates,” says Lars Svensson, MD, PhD, one of the lead PARTNER 2A investigators. “For instance, Cleveland Clinic’s surgical AVR mortality over the past five years is less than 0.5 percent. Expert centers’ ability to offer strong outcomes like this with both TAVR and surgical AVR means these centers’ heart teams can now direct patients to the best approach for their individual circumstances.” And such choice may be on the horizon for low-risk patients as well, with the ongoing PARTNER 3 trial assessing TAVR with the SAPIEN 3 valve versus surgical AVR in aortic stenosis patients at low surgical risk. For more, see this post.

Robot-assisted mitral valve repair makes a claim on standard of care

When researchers presented Cleveland Clinic’s experience across its first 1,000 robotically assisted mitral valve surgery cases at the AATS meeting in May, they revealed a mortality rate of just 0.1 percent (1/1,000) and a procedural success rate exceeding 99 percent. “Despite reports documenting the safety and efficacy of robotically assisted mitral valve repair, it hasn’t become the standard of care for managing mitral valve disease,” says lead researcher A. Marc Gillinov, MD. “These results may help change that, as we’ve shown that robotic surgery enables mitral valve repair with high procedural success and low morbidity and mortality.” What’s more, the study showed that procedural safety and effectiveness improved with increasing experience and the application of algorithm-driven patient selection. For more, see this post.

First transcatheter tricuspid valve replacement

Percutaneous heart valve replacement expanded to a new front in November when a Cleveland Clinic team successfully performed the world’s first implantation of a transcatheter tricuspid valved stent. The recipient was a 64-year-old woman with severe tricuspid regurgitation, which invariably leads to lethal right heart failure. The patient was faring well 30 days after the procedure. “This is a step forward in the minimally invasive treatment of tricuspid regurgitation,” says cardiac surgeon Jose Navia, MD, who led the team. “The hope is to provide a device that is able to capture the diseased tricuspid valve annulus, which has been enlarged inordinately by the ravages of functional tricuspid regurgitation, causing reverse flow of venous blood from the right heart that should go to the lungs.” The novel device, based on a stent technology platform developed at Cleveland Clinic, features a diffuser that enables it to be easily threaded through the vasculature to reach atrioventricular valves and avoid protrusion into adjacent chambers. For more, see this post.

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PRECISION upends assumptions on NSAIDs and the heart

Data from the long-awaited PRECISION trial released in November showed that despite concerns to the contrary, the sole remaining selective COX-2 inhibitor in the U.S., celecoxib, doesn’t confer excess cardiovascular (CV) risk compared with two widely used nonselective NSAIDs. In fact, celecoxib was associated with fewer CV adverse events than both naproxen and ibuprofen in the 24,000-patient multicenter study and appeared to have lower rates of GI and renal adverse events and all-cause mortality. “PRECISION shows unequivocally that CV risk with celecoxib was not greater than with the older nonselective NSAIDs naproxen and ibuprofen,” says Cleveland Clinic’s Steven Nissen, MD, who chaired the study. “In fact, celecoxib was arguably the safest of the three NSAIDs studied.” He adds that while the trial has broad implications, it was limited to individuals taking chronic daily prescription-strength NSAIDs for at least 18 months and did not address occasional use of over-the-counter NSAIDs. For more, see this post.

Leadless pacing comes into its own

2016 witnessed FDA approval of the first leadless pacemaker — Medtronic’s Micra™ — in April, and approval of another leadless pacemaker — St. Jude Medical’s Nanostim™ — is anticipated shortly as well. At the Heart Rhythm Society meeting in May, investigators with the LEADLESS II clinical trial of Nanostim presented an analysis comparing acute and mid-term adverse event rates from LEADLESS II with those observed with transvenous pacemakers from a large U.S. insurance database. They found that patients receiving the leadless device in the trial had significantly fewer infectious and lead-related complications than did patients implanted with transvenous pacemakers in real-world practice. “This analysis debunks the argument that leadless pacing is unnecessary because complications with transvenous systems are very low across the board,” says Cleveland Clinic’s Daniel Cantillon, MD, a LEADLESS II investigator (Cleveland Clinic has been a leading center in trials of the Micra device as well). “Leadless pacing can potentially eliminate the most common sources of complications — the surgical pocket and the lead.” For more, see this post.

Sex-specific clinical and exercise risk scores improve mortality prediction

A new risk-scoring tool that accounts for patient gender raised the bar in 2016 for predicting mortality risk for patients undergoing exercise treadmill testing. The scoring system (available via a free online calculator) was developed at Cleveland Clinic to address shortcomings of established instruments like the Duke Treadmill Score and the Lauer nomogram. “Our aim was to develop comprehensive sex-specific risk scores to estimate all-cause mortality in a more inclusive and contemporary population,” explains cardiologist Leslie Cho, MD, who led the effort. She and colleagues retrospectively analyzed a cohort of 60,000 Cleveland Clinic patients undergoing symptom-limited treadmill testing to derive and validate separate risk scores for men and women. External validation was done in a 49,000-patient cohort from Detroit’s Henry Ford Hospital. As reported in JAMA Cardiology in October, validation studies in both cohorts showed the new sex-specific scores to offer significantly superior risk stratification compared with the older Duke and Lauer instruments, with particular advantages in identifying patients at highest risk of death. “Our data support considering a sex-specific approach when assessing the prognosis of patients undergoing exercise testing,” says Dr. Cho. For more, see this post.

COMMENCE completion heralds new era in valve prostheses

The end of 2016 marked the primary completion date of the multicenter prospective COMMENCE trial, which is evaluating a leaflet treatment technology that promises to revolutionize biological valve treatments. The leaflet tissue treatment platform is based on a method developed at Cleveland Clinic and now used in a pair of investigational bioprosthetic valves being studied in COMMENCE. The trial has enrolled more than 750 adults requiring replacement of a diseased or damaged native or prosthetic aortic or mitral valve. Follow-up through postoperative year 5 aims to see if the new prosthesis technology extends valve life by thwarting valve deterioriation and complications. “These new valves hold the promise of better long-term durability in younger patients,” says Cleveland Clinic’s Lars Svensson, MD, PhD, a principal investigator for COMMENCE. Results are expected within the next year or so.

First bioresorbable stent for CAD makes it to market

The FDA’s approval of the Absorb™ device in July brought the first fully bioresorbable stent to the U.S. market for treatment of coronary artery disease. While the dissolvable device’s combination of transient vascular scaffolding and local drug delivery is an exceptional technical accomplishment, enthusiasm for it has been tempered by clinical trial findings that so far have shown noninferiority — but not superiority — to permanent drug-eluting metal stents. And three-year results of the ABSORB II trial, released in November, showed a signal for higher rates of target vessel MI with the bioresorbable stent than with its drug-eluting metal comparator. So the cardiology community awaits the next report from the 2,000-patient ABSORB III trial, which continues through 2019. “The payoff from bioresorbable scaffolds, if there will be one, is going to be late,” says ABSORB II co-principal investigator Stephen Ellis, MD, of Cleveland Clinic. “We’re looking carefully to see what happens to patients as they go beyond two to three years.” For more, see this post.

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Abundant advances in aortic arch repair

Frozen elephant trunk repair combines open surgical techniques (and the advantages of durability and controlled brain protection) with less-invasive endovascular stentgraft techniques to address the complexities of repairing the aortic arch. Cleveland Clinic surgeons have been leaders in developing these techniques, and 2016 saw three important developments. One is progress toward a more simplified strategy for this extended operation in patients with acute type A dissection — i.e., the B-SAFER (Branched Single Anastomosis Frozen Elephant trunk Repair) technique — which is being presented at the Society of Thoracic Surgeons 2017 annual meeting in Houston. This operation combines direct delivery of a stentgraft device into the downstream aorta with creation of a branched stentgraft into the left subclavian artery during open surgical aortic repair. Second, Cleveland Clinic cardio-aortic surgeons were the first in the U.S. to use an investigational commercial device designed for frozen elephant trunk repairs (Thoraflex™, Vascutek). Finally, enrollment in several studies of new endovascular devices continued apace at Cleveland Clinic in 2016. “The devices are designed with built-in branches — some single- and some double-branched — to accommodate all or portions of the aortic arch in patients with arch disease at high risk from open or hybrid repair,” says Cleveland Clinic Aorta Center Surgical Director Eric Roselli, MD, who is leading the trials with Matthew Eagleton, MD, Aorta Center Interventional Director.

PCSK9 inhibitors continue to impress despite lingering cost concerns

Results from the multicenter GLAGOV trial unveiled in November showed that PCSK9 inhibitors continue to demonstrate unprecedented lipid-lowering potency, raising hopes for their clinical outcome trial results, due in 2017. In GLAGOV, the first intravascular ultrasound study of a PCSK9 agent, evolocumab produced unequivocally greater atheroma reductions than placebo in coronary artery disease patients receiving optimized background statin therapy. After 18 months of therapy, mean LDL cholesterol was 36.6 mg/dL in evolocumab recipients versus 93.0 mg/dL in placebo recipients. “No one’s ever reached levels that low in a clinical trial,” notes Cleveland Clinic’s Steven Nissen, MD, who chaired the study. The LDL levels were associated with a reduction in percent atheroma volume for evolocumab but not placebo and with significantly more patients showing plaque regression in the evolocumab group. “While we await the definitive outcome trials of evolocumab, this study provides strong evidence that reducing LDL cholesterol to unprecedentedly low levels can reverse disease progression,” says Dr. Nissen. At the same time, adoption of the new PCSK9 inhibitor agents was sluggish throughout 2016 — in no small part because their wholesale acquisition cost remains above $14,000 a year. For more on GLAGOV, see this post.

Glycemic and cardiac benefits of bariatric surgery confirmed out to five years

When five-year data from the STAMPEDE trial were presented at ACC.16 in March, the news was good: The beneficial effects of bariatric surgery on glycemic control in obese patients with type 2 diabetes endured to at least five years, and surgery’s advantage over intensive medical therapy appeared to widen over time. These final results from the randomized trial of 150 Cleveland Clinic patients confirmed those from earlier STAMPEDE reports. What’s more, use of both cardiovascular medications and glucose-lowering drugs was significantly reduced among surgery patients relative to medical therapy patients. Several biomarkers associated with heightened cardiovascular risk were also reduced in surgery patients. “Our findings show continued durability of glycemic control after metabolic surgery plus persistent weight loss and reductions in diabetes and cardiovascular medications at five years,” says lead researcher Philip Schauer, MD. For more, see this post.