First AbioCor Trial Patient Dies
Robert Tools, who was the first patient in the trial of the AbioCor, the world’s first totally implantable heart, died November 30, 2001, after uncontrollable bleeding that led to multi-organ failure. The physicians at the University of Louisville, Ky, who implanted the heart in Mr Tools, age 59, on July 2, 2001, said they had had problems maintaining Mr Tools’ anticoagulation status almost from the beginning of his disease.
Mr Tools, who suffered from serious heart failure after sequential heart attacks, as well as diabetes, was 59 when he underwent the experimental procedure. He lived almost 5 months on the artificial pump. However, the problems with gastrointestinal bleeding began early and continued. On November 11, 2001, Mr Tools suffered a stroke because doctors were unable to continue his anticoagulation medication as a result of continued gastrointestinal bleeding. Surgeons said that malfunction or complications from the artificial heart were not to blame for Mr Tools’ death, which they attributed to the comorbid conditions from which he suffered.
The sixth patient to receive the implantable heart died of uncontrollable bleeding on November 29, 2001, within a day of receiving the artificial organ at St Luke’s Episcopal Hospital, Houston, Tex. Surgeon O.H. Frazier, MD, said the death resulted from coagulopathy related to the patient’s longstanding heart failure and cardiac surgery that required anticoagulant treatment.
If nothing else, the 2 deaths demonstrate that much remains unknown about the place such devices will take in the armamentarium of weapons against heart disease. In the past, artificial hearts and ventricular assist devices have been limited to use as a “bridge to transplantation,” for those patients who qualify for a donated human heart but whose illnesses put them at risk of dying before they receive a heart.
The AbioCor trial was an attempt to use such devices permanently in patients who are not transplantation candidates. It is an all-or-nothing attempt because the individual’s native heart is totally replaced, and there is nothing available to take up pumping once the artificial organ fails.
The total artificial heart and ventricular assist devices have had waxing and waning fortunes since the 1960s, when the first implantations of such devices were performed. Problems with blood clots, power sources, and reliability have taken their toll as researchers have doggedly continued their research into determining which device would be best.
Now, perhaps, each type will find a place benefiting a specific set of patients, said Dr Frazier during a discussion at the 2001 Scientific Sessions of the American Heart Association in Anaheim, Calif. “It won’t be this or that,” he said.
Niacin-Simvastatin Combination Benefits Patients With Coronary Artery Disease
Patients with coronary artery disease benefited from the LDL level–lowering effects of simvastatin and the HDL level–increasing effects of niacin in a study published in the November 29, 2001, issue of the New England Journal of Medicine (N Engl J Med. 2001;345:1583–1592). The authors were led by B. Greg Brown, MD, PhD, of the Division of Cardiology at the University of Washington School of Medicine in Seattle and were affiliated with that school, the Oklahoma Medical Research Foundation in Oklahoma City, Okla, and the departments of Pathology and Laboratory Medicine at the University of British Columbia in Vancouver, Canada.
In the study, 160 people with coronary artery disease and low HDL levels were randomized to 1 of 4 groups that received one of the following: niacin and simvastatin; antioxidants alone; niacin and simvastatin plus antioxidants; or placebo. The effects of the treatment were evaluated according to the amount of coronary artery stenosis, blood cholesterol levels, and the frequency of cardiovascular events such as myocardial infarctions or strokes.
The LDL and HDL levels in the antioxidant and placebo groups were unaltered. The average stenosis increased by 3.9% with placebo and 1.8% with antioxidants. In the simvastatin-and-niacin group, the LDL levels went down 42% and the HDL levels increased 26%. The stenosis levels increased 0.7% in those patients who received simvastatin, niacin, and antioxidants. However, stenosis regressed 0.4% in the group that took simvastatin and niacin alone.
In the placebo group, 24% of patients suffered heart attacks or stroke, and 21% of those in antioxidant group suffered a similar fate. However, only 3% of the group receiving simvastatin-niacin and 14% of the group receiving simvastatin-niacin plus antioxidants reached the clinical end points.
The results for the groups receiving placebo or antioxidant alone were not surprising, but the results for the group receiving niacin, simvastatin, and antioxidant were. “When antioxidants were combined with simvastatin and niacin, arterial and clinical benefits tended to diminish as compared with those achieved with simvastatin and niacin alone,” the authors wrote. “The adverse interaction between these 2 therapeutic strategies was significant in terms of the angiographic end points but not in terms of the clinical end points. This interaction appears to result from substantial and specific blunting by these vitamins of the expected increase in the level of the protective HDL2 subfractions—an effect that has been found with the potent nonvitamin antioxidant probucol.”
Folate Reduces Homocysteine Levels and Lowers Rate of Restenosis
Treating coronary angioplasty patients with folic acid, vitamin B12, and pyridoxine reduces homocysteine levels significantly and lowers the rate of restenosis and the need for repeat revascularization, according to the authors of a study that appeared in the November 29, 2001, issue of the New England Journal of Medicine (N Engl J Med. 2001;345:1593-1600).
A total of 205 patients were randomized to treatment with 1 mg folic acid, 400 μg of vitamin B12, and 10 mg pyridoxine (called folate treatment) or to placebo for 6 months. The researchers were led by Guido Schnyder, MD, of the Cardiology Division of the University of California at San Diego Medical Center in California; others who participated in the study included physicians and scientists from the Swiss Cardiovascular Center at the University Hospital in Bern, Switzerland, and the Kardiologische Praxis in Bremen, Germany.
The primary clinical end point was restenosis within 6 months, and a secondary end point was one of a combination of major adverse cardiac events. The study was an attempt to address the problems presented when 10% to 40% of patients who undergo percutaneous coronary angioplasty suffer restenosis within 6 months. In a previous study, researchers said they had associated reduced homocysteine levels with reduced rates of restenosis. In this study, they attempted to determine if they could reduce the incidence of reclogging when they reduced homocysteine levels with the use of medication.
They found that that folate treatment significantly reduced homocysteine levels from 11.1 to 7.2 μmol/L. The minimal luminal diameter of the target artery was significantly larger in the group assigned to the folate treatment, as well (1.72 mm in the treatment group versus 1.45 mm in the placebo group). The degree of stenosis was also less severe in the treatment group compared with the placebo group (39.9% versus 48.2%).
In addition, the rate of restenosis was lower in patients assigned to folate treatment—19.6% in the treatment group versus 37.6% in the placebo group. They recommended consideration of the inexpensive treatment, which has minimal side effects, in patients undergoing coronary angioplasty.