Dick Cheney's 30-year CHD odyssey approaches transplantation crossroad

March 31, 2011

Washington, DC - "Many of the opportunities I've had would never have come to me at all were it not for steady advances in the practice of cardiology," said the former US congressman, secretary of defense, and vice president[1].

Former Vice President Dick Cheney

"I guess what I'm saying is that, for those who wish Dick Cheney had called it quits a long time ago, they can blame it all on you."

Addressing cardiologists and other vascular-disease specialists, donors, and dignitaries in 2009 at an annual dinner sponsored by the Baylor Health Care System Foundation, Richard B Cheney described—with humility and humor—a battle with heart disease over more than three decades that had included four heart attacks, the first striking when he was only 37.

Weapons brought to bear against his coronary disease over the years, at least those known to the public, included coronary stents, bypass surgery, external cardioversion, and implantable cardioverter-defibrillators.

While specifics have seldom if ever been detailed for the public, Cheney was in all probability sustained through the decades by an evolving state-of-the-art medical therapy aimed at, among other things, his sky-high serum cholesterol and progressively stormy renin-angiotensin system.

Less than a year after his Dallas speech, a version of which was published in the July 2009 Baylor University Medical Center Proceedings, Cheney would suffer a fifth heart attack, described for the public as "mild" but possible a turning point in his clinical course. His heart failure worsening, punctuated by acute exacerbations, Cheney—one of the most powerful and controversial figures in recent US history—would in the summer of 2010 be implanted with a continuous-flow ventricular assist device (VAD) that had only months before been approved by the FDA for destination therapy, the HeartMate 2 (Thoratec).

In late January of this year, days before his 70th birthday, Cheney—appearing fairly healthy despite looking considerably thinner than when he was in office—opened up about his VAD for the media and announced that he was still contemplating whether he would pursue what is seen as the definitive therapy for heart disease as advanced as his: transplantation.

A deserving candidate

Dr Mandeep R Mehra

"Dick Cheney's history displays the entire continuum of cardiovascular disease. His story is a classic reflection of how one goes from risk factors to the interim sequela of structural heart disease, to the ultimate sequela of cardiac failure, to the opportunity for restorative therapies," observed Dr Mandeep R Mehra (University of Maryland School of Medicine, Baltimore) for heartwire .

Mehra, a recent past president of the International Society for Heart & Lung Transplantation, said given the limits of what is publicly known about Cheney's history, assuming he isn't diabetic or has other major contraindicating comorbidities, "I really think he would be a very deserving candidate for cardiac transplantation at this point."

 
Age has to be rethought as a contraindication for cardiac transplantation. Many of us now believe that with an aging society, absolute cut offs for age are irrelevant.
 

His two main options are "let him stay with the VAD as palliative therapy, which used to be called destination therapy, or bridge him to transplantation," he said. "Bridging to transplantation would be wise, except that he has just crossed the age of 70, and most of us become a bit leery of offering transplantation once the person has crossed the age of 70."

But there's no absolute age cutoff for placement on a wait list, Mehra observed. "Age has to be rethought as a contraindication for cardiac transplantation. Many of us now believe that with an aging society, absolute cutoffs for age are irrelevant. What should be relevant is the ability to functionally contribute to society and have a meaningful life after transplantation."

Dr Randall C Starling

Still, age is "probably the hot button" with Cheney's case, agreed Dr Randall C Starling (Cleveland Clinic, OH), who is head of heart failure and cardiac transplant medicine and medical director of his institution's Kaufman Center for Heart Failure. It's hard to pin down the age limit for transplantation at any one center, he observed for heart wire , but it's possible to look up how many patients over age 65 are transplanted at any given center. "Most of the large centers now probably have 10% to 15% of their [heart-transplant] patients over age 65," Starling said.

"I would say that most centers look at age as another risk factor and start to get nervous when patients are over 65 or 70." When such patients are transplanted, survival goes down, he said. "His age would be a component of his overall profile and would enter into a center's evaluation of his options. If you asked me, have we transplanted patients who are over age 70 here [at the Cleveland Clinic], the answer would be yes. I don't think that age as an individual variable would close the door at most transplant centers."

A defining moment

It's difficult to know where Cheney was clinically when he received the VAD, but there are indications he had been in heart failure for many years. It was a top story in the summer of 2001 when—a few months after becoming vice president, a bout of unstable angina, and subsequent coronary stenting—he underwent electrophysiologic testing followed by implantation of his first ICD.

"That was a bit of a defining moment, as it indicated that his ejection fraction had to be in the 35% range or lower," Starling said.

Cheney's heart and circulation were occasionally big news throughout his term: likely chronic heart failure possibly with some bouts of decompensation in 2006, treatment for deep-venous thrombosis in March 2007 soon followed by ICD replacement, and cardioversion for AF in November 2007 and October 2008.

 
He most certainly got the best medical care, and so I consider him a striking success of heart failure therapy.
 

But there wasn't a lot of public news about a decline in health from the end of his term in January 2008 until he was implanted with an LVAD, except for a "minor heart attack" in February 2010. "So I was a little surprised that he had progressed to that point," Starling said.

"It always amazes me, the severity of heart disease that patients have when we drill down on their case, despite the relatively normal degree of activity they can maintain. Patients can have very low ejection fractions and abnormal hemodynamics and still feel like they're getting by pretty well. But the next little thing that comes along, whether it's an arrhythmia, another little heart attack, or whatever—it takes almost nothing to tip them over the edge. I suspect he was probably more in that situation."

Another possibility, Mehra speculated, is that "he was probably sicker than we were all led to believe while he was in office. They never truly outlined his severity of illness or how symptomatic he was. But my suspicion is that he had been sicker because after he left office, his condition quickly progressed to needing an LVAD."

"A striking success" for heart-failure therapy

Dr Barry H Greenberg

Also speculating for heart wire , Dr Barry H Greenberg (University of California, San Diego) said the drugs Cheney took were not discussed much publicly but he was likely on excellent medical therapy the entire time. Noting that he held a series of high-profile, exceptionally stressful positions as he fought heart disease throughout half his lifetime, Greenberg said that it appears "the curve of the natural history of his disease was altered significantly by all the interventions that were done, up to and including placement of the HeartMate 2."

Greenberg, who directs the advanced heart-failure treatment program at his center, observed that Cheney "was a vigorous public figure for many years. . . . He most certainly got the best medical care, and so I consider him a striking success of heart-failure therapy."

He would want to know Cheney's renal function and comorbidities, Greenberg said, but otherwise, "if he walked into my office, I certainly would not exclude the opportunity for transplant for him just based on his age."        

Prospects on a VAD

"Now that he's had an LVAD in for about eight or nine months, he's sort of reaching the phase of LVAD therapy where the thromboembolic risk is high and a decision must be made," according to Mehra. The annualized risk of disabling stroke in NYHA class 3 heart failure is only about 1%, but in patients with the latest generation of VADs it is "somewhere in the realm of 12%," he noted. That makes VAD support more appealing for short-term support if transplantation is at least a possibility.

"On a HeartMate 2 we can count survival to two years, which is about 58%, or we can count survival to three or four years, even, with a device change. But the fact is that nothing right now has the track record of cardiac transplantation, which has a median survival of 10 years," he said. "If we do not consider transplantation in him, right now his chances of a meaningful five-year survival are almost nil."

 
At age 70, the rigors of going through the posttransplant period have got to be less appealing than they'd be for someone who is 35.
 

On the other hand, based on data from the manufacturer, Starling speculated that the HeartMate 2 pump itself could potentially last five or 10 years or more in a patient, if all else goes well. And, "barring a breach in the patient's therapy, Coumadin or other forms of anticoagulation," once the patient gets past the first year or so, the risk of the worst potential complications like thromboembolic stroke or intracranial hemorrhage may go down.

"It's not unheard of that people get a HeartMate 2 with the intention of progressing to the transplant list, and they find that the lifestyle that's afforded by [VAD support] seems acceptable to them," according to Greenberg. "Transplantation is very rigorous. You're put on very potent immunosuppressant drugs that increase the likelihood of opportunistic infections; cancers are more common because of this immunosuppression. At age 70, the rigors of going through the posttransplant period have got to be less appealing than they'd be for someone who is 35."

Indeed, Cheney's current eligibility for transplantation depends on whether he is free of major comorbidities, Greenberg noted. "Has he developed significant renal problems? Has he developed significant pulmonary problems?"

Possible bars to transplantation

Mehra pointed out some red flags in Cheney's history that could influence how suitable he'd be for transplantation. He apparently has some form of genetic hypercholesterolemia—in his Baylor speech, Cheney notes that when evaluated after his first heart attack, he had "a cholesterol reading above 300." And previously, his grandfather "had a sudden heart attack, and he didn't make it."

 
20% to 30% of patients that receive an LVAD with an intention of chronic therapy wind up on a transplant list.
 

"Specific attention would have to be paid to ensuring that he doesn't have peripheral vascular disease, say in the aorta, his cerebrovascular system, or in his limbs. I think those would be important issues to investigate. We don't know how his kidneys are behaving, and we don't know what his lung pressures are," Mehra said. After Cheney's fifth heart attack and subsequent hospitalization for heart failure, "I do know that the decision to proceed with a VAD was based in the setting of significant renal dysfunction."

If Cheney received the VAD for palliation because comorbidities rendered him ineligible for transplantation—and he's now considering transplantation—it's possible that VAD support has somewhat reversed his clinical deterioration.

"You'll see that 20% to 30% of patients that receive an LVAD with an intention of chronic therapy wind up on a transplant list," according to Starling.

VAD use on the prospect of converting transplant ineligibility to eligibility would be considered "bridge to eligibility" or "bridge to decision," relatively new terms.

"Bridge to decision is typically entertained in patients with severe pulmonary hypertension or in those with at least moderate-stage renal dysfunction," Mehra said. "Because many of those patients do recover."

Mehra discloses receiving consulting fees from St Jude Medical, Medtronic, and Geron; he has previously disclosed receiving research grants or consulting fees from XDx. Starling r eport s receiving research support from Thoratec , being a member of the clinical adjudication committee for the HeartWare destination therapy trial ENDURANCE , consulting or speaking for Medtronic, and being an unpaid board member for United Network of Organ Sharing . Greenberg has participated in speaker ' s bureaus for GlaxoSmithKline, Novartis, and Merck and served as a consultant or advisor for GlaxoSmithKline, Novartis, and Sanofi-Aventis.

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