JMSA JOURNAL VOL. 5 NO. 1
Japanese Medical Society of America
M. Adachi, M.D., Sc.D. and J. Furuyama, D.D.S. (Editors)
Heart Transplantation, Artificial Heart, and Device Lag
Hiroo Takayama, M.D., Ph.D., Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Medical Center
Heart failure (HF) remains one of the most common causes of death in the United States. The 2005 ACC/AHA guidelines introduced a comprehensive and systematic method of assessing and managing patients with risk factors and those with HF. The suggested staging system is ambitiously inclusive, covering a wide range of patients with cardiovascular problems. It categorizes patients into Stages A (at high risk for HF but without structural heart disease or symptoms of HF) to D (refractory HF requiring specialized interventions). Medical treatment is extremely limited for HF patients in Stage D. Among the available surgical interventions for HF, left ventricular assist device (LVAD) is distinct from the others in that it, at least partially, replaces the pump function of the failing heart, similar to heart transplantation. Unlike heart transplantation, however, it does not rely on a human donor supply, which is a well-known limiting factor. As technological advances have accrued, LVAD has evolved into a reliable and well-described treatment option.
Mechanical support of the cardiopulmonary system was first clinically introduced by John Gibbon in 1953, when he first successfully employedcardiopulmonary bypass for the repair of an atrial septal defect in the US.In 1963, DeBakey, the legendary US cardiac surgeon, implanted the first VADin a patient who suffered cardiac arrest following aortic valvereplacement. The patient subsequently died on postoperativeday 4. The National Heart, Lung and Blood Institutebegan funding initiatives to pursue thedevelopment of more advanced LVADs and a total artificial heart. This led to continuing advancesin the development of LVADs.
Early survival data of patients undergoing LVAD insertion revealed greater than 30% hospital mortality. Advancements in perioperative care and technology have led to improvements in outcomes, and this culminatedin FDA approval of an LVAD as a bridge therapy for heart transplantation in 1994. Newer generation LVADs have been developed to overcome the limitations of the first generation pumps. These pumps are characterized by continuous flow driven by a rotary pump. These continuous-flow second and third generation pumps generate low grade pulsatility as opposed to the first generation ‘pulsatile’ pumps with volume displacement. Outcome of device therapy on HF patients made tremendous forward step with continuous-flow LVAD technology. LVAD implantation is now the standard therapy for end-stage HF. Among various continuous-flow LVADs, HeartMate II LVAD (Thoratec, Inc., Pleasanton, CA) has the largest track record of clinical use. Since its first use in 2000 in Israel, over 10,000 patients received this pump worldwide. This device was approved for clinical use in 2005 in Europe (CE Mark) and in 2009 in the USA (FDA).
To our disappointment, there was a long delay in gaining approval for the use of this device in Japan despite the fact that it was the standard therapy in the western world. This phenomenon is called ‘device lag’. Above being said, two devices with similar technology were finally approved for clinical use at the end of 2011, and these devices have been gaining in popularity. Until then, patients with end-stage heart failure who would have received implantable continuous-flow LVAD in the western countries, had to either die or receive a first generation LVAD which comes with heavy apparatus and mandates hospital stay. Patients with this first generation LVAD are tethered to the apparatus all the time. The device lag in Japan very likely resulted in loss of many lives and major loss of quality of life. Approval of a new medical device requires clinical trial and application for the Pharmaceuticals and Medical Devices Agency: PMDA. Since the PMDA plays a major role in all three steps, one could easily blame the Japanese bureaucratic system for the ‘device lag’.
The following are thought to be the main reasons for ‘device lag’:
1. Conducting a clinical trial is difficult in Japan:
a. Japanese market is becoming smaller compared to those of other countries.
b. Manufacturers have to cover the expense.
c. Manufactures’ and medical providers’ concern for the law suit for PL and medical error.
d. Very low recognition and appreciation of clinical trials in Japanese society.
2. At approval:
a. Bureaucratic system
b. Conservative system
c. Heavy blame from the society at occurrence of clinical complications related to new device even if they may have been unexpected.
I would like to point out the role of the ‘society’ in device lag. The Japanese society in general has minimal tolerance for mistakes. For example, in the U.S. when one is trying to establish a phone connection at one’s new house through a telephone company, it takes a long time to get it done. The workers in the company do not answer your call appropriately, do not show up at the appointment in time, and frequently have not much idea about the situation even if they show up. And they are rude! They will say ‘I wasn’t there’ or ‘I didn’t say that. We all get annoyed by the poor work ethics and the irresponsible attitude of the some of the U.S. workers. The Japanese workers, on the other hand, put the customers above themselves all the time (at least in public), and try to take the responsibility even when the problem has nothing to do with what they are supposed to do. The Japanese society, made up of diligent people, is a very tight social space, whereas the US society is much looser. In the “tight” Japanese environment, blame is always put on someone for their mistakes, and this I believe is one of the main reasons for ‘device lag’. Should Japanese society request resolution of device lag, we need to accept the idea of ‘to err is human’ and recognize the fact of ‘no risk, no gain.’