Further Innovations in Diastolic Augmentation, 1968-2008
His two attempts to implant his first LVAD model in 1966 showed Kantrowitz that a truly successful permanent implant would require much further work. He decided to focus instead on developing a temporary ventricular assist device that could be placed within the aorta to provide counterpulsation. He believed that such a device might prevent death from cardiogenic shock following a heart attack, and allow the damaged part of the heart muscle to heal. One in five heart attack victims goes into shock--rapidly falling blood pressure and insufficient circulation triggered by the trauma to the heart--and the already-damaged heart suffers further as it tries to keep the circulation going. In the late 1960s, about 85 percent of such patients--an estimated 100,000 per year--died of cardiogenic shock.
Several other investigators working in the early 1960s had been able to augment circulation in dog studies using long thin balloon pumps inserted into the aorta, but problems with materials and methods discouraged their pursuit of the work. Kantrowitz's team designed an intraaortic balloon pump (IABP) of non-distensible polyurethane inflated with helium. The uninflated balloon and its air tube were threaded up the femoral artery and into the thoracic aorta. The tube was connected to an automatic pump, which received signals from the patient's EKG monitor. Just after the heart contracted, forcing blood into the aorta, the EKG signaled the pump to inflate the balloon. The expanding balloon forced blood back toward the heart and into the coronary arteries, and gave an extra push to blood going out the aorta to the rest of the body. The balloon then deflated until just after the next heart contraction. When the patient recovered from shock and the heart could take over circulation, the balloon could be withdrawn through the incision in the femoral artery.
By early 1967, successful animal experiments encouraged Kantrowitz to proceed to clinical trials on a small number of patients suffering from cardiogenic shock. His first patient was stabilized after seven hours on the balloon pump, recovered from her heart attack and was discharged. The second two attempts failed; in one case the balloon couldn't be inserted, due to an aortic aneurism, and in the other, the pumping was successful, but the patient went into cardiac arrest when they tried to reposition the pump. During the next year, Kantrowitz used the IABP in twelve more cases; in five of these the patients recovered and were discharged. In all the cases the device reversed the cardiogenic shock, even if the heart was too damaged to recover.
His publications and presentations on these initial trials drew many inquiries from colleagues eager to try the IABP. In 1969, Kantrowitz began planning a multi-institutional cooperative clinical study to evaluate the device. The research committee at Maimonides Hospital however, refused to approve the cooperative study protocol for further clinical trials there, expressing doubt about the IABP's effectiveness. This clash over the IABP study pushed the relationship between Kantrowitz and the hospital administrators to the breaking point. The trail-blazing surgeon had brought the community hospital much publicity with his attempts to implant his early pacemakers, and the first LVAD, and finally with the transplants. The administrators, perhaps weary of the high-profile risk-taking, asked Kantrowitz to find another institutional base. Offered several appointments, he chose Sinai Hospital of Detroit, which had just opened a new research facility and was planning an open-heart surgery program. He was able to take his NIH research funding and the IABP cooperative study with him. Almost all of his team from Maimonides (25 people) elected to move to Detroit with him, so he was able to reconstitute his research and surgical units there very quickly. Kantrowitz also joined the clinical faculty of Wayne State University School of Medicine, a post he held until 2008.
The cooperative study of the IABP, comprising 87 cases, finished in 1973, and demonstrated the efficacy of the device for some cases of cardiogenic shock. The survival statistics were not especially positive; in many cases the heart attack had caused too much damage for the IABP to improve the patients' outcome. Only about 20 percent of heart attack patients had enough viable heart muscle left to recover their ventricular function, but in these cases the IABP worked very well. Though not an outstanding tool for saving heart attack patients, Kantrowitz's IABP has since the 1980s been widely adopted for supporting patients with unstable angina, and for weaning patients from heart-lung bypass after cardiac surgery.
The IABP inspired the design of Kantrowitz's second-generation LVAD, which he called the "dynamic aortic patch." It consisted of an elliptical silicone rubber chamber covered with Dacron fabrics, attached to an inflation tube. It was inserted into the aorta, then sutured into the aortic wall. Internal EKG leads and the inflation tube ran out through the skin to an external power unit, which inflated the patch during diastole to push extra blood to the coronary arteries and the rest of the body, just as the IABP did. After several years of animal experiments, Kantrowitz tried the device in three patients bedridden with heart disease. The first patient received the LVAD in August of 1971 and improved enough to go home and pursue normal activities for several months. He died from an infection contracted through the LVAD access site; the LVAD was found to be free of clots or other problems. A second patient survived 64 days, but also died of an infection acquired via the access site. Although the LVADs performed well, the infection problem was discouraging. Kantrowitz stopped clinical trials and resumed animal studies.
Working with researchers at the University of Michigan, the Kantrowitz team spent many years refining the dynamic aortic patch and developing a percutaneous access device (PAD) that would prevent infection by providing a mechanical bond and a biological seal between the access port and the surrounding tissue. They did this by culturing specialized skin cells from the intended patient, then growing them onto a specially prepared port. Once implanted, the device surface merged with the patient's dermal layer, creating a barrier to fluids and microbes, and preventing the skin's epidermal layer from interfering with the site. The PAD design also reduced mechanical stress that could disrupt the tissue-device seal. They tested several variations of the PAD on miniature Yucatan pigs (chosen for their close similarities to human skin); though there were problems with infection and the structure of the device, three of the cell-coated PADs remained intact in the pigs for over five years with no sign of infection. Between 1997 and 2007, Kantrowitz did a small feasibility study of his latest LVAD (the Kantrowitz Cardio-VAD) using the PADs with good results on terminally ill patients. In 2008, he obtained FDA approval for expanded clinical trials. Unlike most other LVADs, the Kantrowitz devices are valveless and "non-obligatory," i.e., they can be turned on and off as the patient requires. Continuous-flow LVADs, such as those developed by Michael DeBakey and Robert Jarvik, require the pump to be working constantly; if it malfunctions, the patient's heart might or might not re-start on its own. Both types of LVAD can be used to sustain patients waiting for heart transplants.
Kantrowitz died on November 14, 2008, of congestive heart failure, having devoted much of his life and his enormous energy to revolutionizing the treatment of cardiac disease.