Ann Thorac Surg 2009;88:344-347. doi:10.1016/j.athoracsur.2009.02.082
© 2009 The Society of Thoracic Surgeons
Our Surgical Heritage
Bhagavant Kalke and His Pioneering Work on the Bi-Leaflet Heart Valve Prosthesis
Pankaj Saxena, MCh, DNBa,
Igor E. Konstantinov, MD, PhDa,b,*
a Department of Cardiothoracic Surgery, Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia
b Cardiac Surgery Unit, Royal Children's Hospital, Melbourne, Australia
* Address correspondence to Dr Konstantinov, Royal Children's Hospital, Parkville, Victoria, 3952, Australia (Email: igor.konstantinov{at}rch.org.au).
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Introduction
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Bhagavant R. Kalke, working with C. Walton Lillehei (1918–1999) at the University of Minnesota, designed the first bi-leaflet heart valve prosthesis in 1965. This prosthesis became known as the Kalke-Lillehei valve and was implanted clinically in 1968. Although this valve did not find further clinical application, Kalke's design laid a foundation for the development of all modern bi-leaflet prostheses. Demetre M. Nicoloff (1934–2003) subsequently used this innovative concept and perfected Kalke's original design into the modern bi-leaflet mechanical prosthesis. Today, the bi-leaflet mechanical valve is the most commonly used heart valve prosthesis in the world.
Although a number of heart valve substitutes were designed in the early 1960s, a reliable prosthetic valve was yet to be found [1, 2. This was the time when young Dr Kalke entered the scene of cardiac surgery. The details in this paper are based on a personal interview that we conducted with Dr Kalke.
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From Mumbai to Minneapolis
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Bhagavant Rajaram Kalke was born to a middle class family on November 24, 1927, in the small village of Kasheli in the Ratnagiri District, which is in the Indian state of Maharashtra. The family moved to Bombay (now Mumbai) when Bhagavant was 10 years old. Upon his graduation in 1952 from Seth Gordhandas Sunderdas Medical College, Kalke (Fig 1) continued his surgical training at Nair Hospital. Kalke developed an interest in cardiac surgery after reading about the pioneering work done by Clarence Walton Lillehei at the University of Minnesota. At that time, cardiac surgery at Nair Hospital was in its earliest stages. The hospital developed an experimental laboratory for open heart surgery, however, that caught the eye of Dr Lillehei during his visit to India in January 1964. Kalke approached Lillehei and asked if he could spend 2 years working with him. Lillehei arranged that, and Kalke arrived in Minneapolis on October 14, 1964. Soon after his arrival, Kalke assisted Lillehei for the first time. Kalke recalled that it was an aortic valve replacement with a Starr-Edwards prosthesis. This bulky prosthesis was implanted with some difficulty.
Kalke thought that it would be more convenient to use a low-profile mechanical prosthesis, particularly in children, and he based the design of a new prosthesis on the tidal floodgates of the dams in his native village in India. As the tide came up high, the floodgates closed, and as the tide receded, the gates opened and drained into the irrigation channel. At the end of 1964, Kalke showed the design of his prosthesis to Lillehei, who agreed to get the valve made at the University of Minnesota workshop. Soon, Kalke proudly brought the first prototype of his valve to Lillehei. After looking at it, Lillehei smiled and said, "Give it a try." Kalke enrolled into the PhD program at the University of Minnesota with the intention to design and test his new prosthesis in Lillehei's laboratory.
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Experimental Trial of Kalke's Valve
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Initially, four valves were made by the workshop. The basic structure of this valve consisted of two semicircular metal leaflets placed in a rigid cage formed by a metal ring. The valves for the experiments were made from stainless steel. Kalke started implanting these valves in dogs in the mitral and aortic positions. Cineangiography was performed on the second or third postoperative day. Normally, Kalke was assisted during these procedures by one of the surgical residents working in the laboratory. A laboratory technician ran the heart-lung machine.
Soon Kalke became aware of another low-profile valve—the Gott-Daggett prosthesis. Vincent L. Gott was a surgical resident who worked with Lillehei from 1953 to 1960. Upon completion of his residency in 1960, Gott became a staff surgeon at the University of Wisconsin. Together with Ronald L. Daggett, an engineer and later professor at the University of Wisconsin, Dr Gott designed a valve made of a silicon-coated Teflon disk with a central superstrut that allowed the flexible leaflets to bend and open in a butterfly fashion [2]. The Gott-Daggett valve was first clinically implanted in 1963. The area of the superstrut in the Gott-Daggett valve was the site of thrombosis, and for this reason, the valve was taken off the market in 1966 [2]. Kalke compared his valve with the Starr-Edwards and Gott-Daggett prostheses in the animal laboratory. In Kalke's valve, both leaflets moved independently, and they opened to 60 degrees, allowing unimpeded flow through the central and lateral orifices of the valve. The hemodynamic performance of Kalke's valve appeared superior to that of the other tested valves. The study was carried out in 65 animals over a period of 8 months.
In 1965, Kalke met Demetre M. Nicoloff, who completed his residency at the University of Minnesota hospital and was appointed as instructor to the Department of Surgery in 1964. Although Dr Nicoloff was interested in Kalke's design, he was never directly involved in Kalke's experiments; however, as a staff member of the Department of Surgery at the University of Minnesota, Nicoloff was appointed to the committee that read Kalke's thesis, and it was approved. Thus, Kalke fulfilled that requirement and was then allowed to present for his preliminary doctoral examination, which he passed on November 24, 1967. On May 30, 1968, Kalke presented a paper titled "Evaluation of a double-leaflet prosthetic heart valve for clinical use" at the Second National Prosthetic Heart Valve Conference in Los Angeles, California. The studies relating to the performance of this valve were published in 1968 and 1969 [3, 4.
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First Clinical Implantation of Kalke-Lillehei Valve
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In 1967, Lillehei accepted an appointment as Lewis Atterbury Stimson Professor and chairman at New York Cornell Medical Center. Lillehei invited Kalke to join his department in New York, and Kalke moved to New York on December 5, 1967.
A few prostheses were fabricated by Harry Cromie (Surgitool Company, Pittsburgh, PA) in 1968 for clinical use [2]. The prosthesis became known as the Kalke-Lillehei valve (Fig 2). Titanium was used as the material, and the sewing ring was covered with Teflon. The first prosthesis was implanted in March 1968 in the aortic position. Unfortunately, the patient died 2 days later; the cause of death was not known. It was a big setback for Lillehei and Kalke. In the meantime, the pressure on Kalke was mounting to go home to Mumbai, as his leave of absence had come to an end. On July 29, 1968, Kalke left for Mumbai. The job of further refining and patenting the valve was left to Lillehei. To some extent, enthusiasm was lost owing to the failure of its first clinical implantation. Lillehei then focused on his tilting disc prosthesis, known as the Lillehei-Kaster valve, which was first implanted clinically in 1970. Robert Kaster, an engineer and a graduate of the University of Minnesota, believed that the ideal disk material was pyrolytic carbon, and he worked with Jack C. Bokros on the fabrication of a flat disk for his valve. Approximately 55,000 Lillehei-Kaster valves were implanted, until production of the valve ceased in 1987 [2].
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Fig 2. Clinical model of Kalke-Lillehei valve with leaflets in (A) open and (B) closed position, and (C) as seen from below.
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For a few years, these events overshadowed Kalke's bi-leaflet prosthesis. Soon, however, Lillehei's interest in Kalke's work was renewed. In February 1973, Kalke received a letter from Lillehei urging Kalke to complete his doctoral degree within the next 3 months. Kalke would need to travel to the United States to complete the doctoral examination. That was not financially possible for Kalke, and he told Lillehei about his inability to travel to Minnesota to complete his doctoral degree. To his surprise, however, the Department of Cardiac Surgery at the University of Minnesota paid all the expenses for Kalke to travel to Minneapolis for his doctoral defense. The thesis submitted to the University of Minnesota was titled "Evaluation of a double-leaflet prosthetic heart valve of a new design for clinical use." Kalke's examiners were Lillehei, Nicoloff, and Jesse C. Edwards. Kalke was awarded his PhD degree in April 1973. Nicoloff was very interested in the design of Kalke's prosthesis and was helpful in reviewing his final doctoral thesis.
Pyrolytic Carbon
Pyrolytic carbon, the world's hardest manufactured substance, has been adapted from the nuclear fuel industry. In 1964, Bokros suggested to Gott the testing of pyrolytic carbon as a prosthetic material. They demonstrated that pyrolytic carbon was the most thromboresistant of all materials available [2]. Pyrolytic carbon revolutionized the mechanical heart valve industry. The fabrication of a hollow ball of pyrolytic carbon for the DeBakey-Surgitool valve in 1969 by Bokros was a landmark in mechanical valve development ([5]). By 1970, it was used for most monoleaflet valves [2]. All subsequent bi-leaflet prostheses were made of pyrolytic carbon, which determined their extraordinary strength and durability.
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Evolution of Bi-Leaflet Prostheses: From Kalke Valve to Modern Prostheses
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In 1976, Christopher Possis, an industrial engineer, and Nicoloff began to develop a prosthetic heart valve. Nicoloff and Possis approached Manuel A. Villafana for the further development of this valve model [1]. On July 4, 1976, Villafana started St Jude Medical Company. Apparently, it was Villafana's idea that the entire valve be fabricated of Bokros' pyrolytic carbon [2]. Nicoloff was an associate professor at the University of Minnesota when, on October 3, 1977, he implanted the first St Jude bi-leaflet prosthesis [6]. Although the original St Jude Medical bi-leaflet prosthesis implanted in 1977 looked very similar to the Kalke-Lillehei valve, it was not, according to Villafana, a "direct descendant" of the Kalke valve [2]. Remarkably, the original design of the St Jude prosthesis implanted in 1977 has remained virtually unchanged over the past 30 years.
In 1979, Lillehei was appointed Director of Medical Affairs at St Jude Medical, a position that he held until his death in 1999. By 1990, more than 320,000 St Jude prostheses had been implanted—more than any other heart valve. St Jude Medical had approximately 46% of the worldwide market for heart valves, and its total sales topped $175 million in 1990. In 1990, Nicoloff and Villafana once again brought back several members of their original scientific group to revisit the St Jude prosthesis, with a goal of further improving its performance. That resulted in the establishment of the Advancing The Standards (ATS) group and the development of the ATS bi-leaflet mechanical prosthesis. On May 4, 1992, Nicoloff assisted Professor Hossein Sadeghi at the University of Lausanne, Switzerland, during the implantation of the first ATS open pivot prosthesis [7].
In 1986, Bokros founded Carbomedics and began production of the Carbomedics bi-leaflet prosthesis, which was similar in design to the St Jude valve but its housing could be rotated within the sewing ring [2, 8. The first Carbomedics bi-leaflet prosthesis was implanted in Paris in 1986. In 1994, Bokros founded the Medical Carbon Research Institute (MCRI) to utilize a new pure form of isotropic carbon to develop new bi-leaflet prosthesis—the On-X prosthetic heart valve—with reduced thrombogenesis. In 2007, MCRI was renamed On-X Life Technologies, Inc. The first On-X prosthesis was implanted on September 12, 1996, by Professor Axel Lacszkovics in Bochum, Germany. Reduced anticoagulation therapy trials of the On-X prosthesis are currently being undertaken. It is not inconceivable to think that the On-X prosthesis may become the first mechanical valve that will not require anticoagulation therapy. The remarkable success story of the bi-leaflet prostheses is yet to be continued.
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Successful Oblivion or Oblivious Success?
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Kalke held the position of dean of Topiwala National Medical College (Fig 3) and was the head of the Department of Cardiovascular surgery at Nair Hospital in Mumbai until his retirement in 1985. Apart from clinical work, Kalke continued with his research work and teaching [9, 10. Upon his retirement, Kalke lived a modest life and was enthusiastically involved in charity and social work. He visited Lillihei several times (Fig 4) and corresponded with him regularly. Most cardiac surgeons had never heard of Kalke. Furthermore, in two major review articles of their results with the St Jude valve from Nicoloff's group, we found no reference to the development of the first bi-leaflet valve by Kalke [6, 11. In 2002, however, Nicoloff acknowledged Kalke's pioneering work in the following line: "In 1967, a young Dr. Kalke working in the lab of Dr C. Walton Lillehei also had a bi-leaflet design but, due to materials, was not able to develop it successfully" [7]. In 2002, St Jude Medical controlled more than 50% of the mechanical heart valve market, and its booked net sales were $1.6 billion. In 2007, St Jude Medical net sales were $3.8 billion. More than 2 million bi-leaflet prostheses have been implanted worldwide. It appears timely to acknowledge Kalke's pioneering work.
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Fig 3. Dr Kalke as Dean of Topiwala National Medical College and Nair Hospital in Mumbai, India, in 1983.
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Fig 4. Drs Kalke and Lillehei at Lillehei's home on October 23, 1988, celebrating Lillehei's 70th birthday in St Paul, Minnesota.
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Acknowledgments
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We are grateful to Dr Kalke for providing us with detailed recollections of his life and events leading to the clinical implantation of the first bi-leaflet mechanical prosthesis and for the original photographs. We are also grateful to Mrs Mamta Sinha, Mr Alok Sinha, and Mrs Alison Wallace for their kind assistance with preparation of the manuscript.
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References
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- DeWall RA, Qasim N, Carr L. Evolution of mechanical heart valves Ann Thorac Surg 2000;69:1612-1621.[Abstract/Free Full Text]
- Gott VL, Alejo DE, Camerone DE. Mechanical heart valves: 50 years of evolution Ann Thorac Surg 2003;76(Suppl):2230-2239.
- Kalke BR, Lillehei CW, Kaster RL. Evaluation of a double-leaflet prosthetic heart valve of new design for clinical useIn: Brewer LA, editor. Prosthetic heart valves. Springfield, IL: Charles C. Thomas; 1969. pp. 285-302.
- Kalke BR, Carlson RG, Lillehei CW. Hingeless double-leaflet prosthetic heart valve for aortic, mitral or tricuspid position Biomed Sci Instrument 1968;4:190-196.[Medline]
- DeBakey ME. Discussion of Braunwald NS, et al. New development in the design of fabric covered prosthetic heart valves. J Thorac Cardiovasc Surg 1971;62:673-682.[Medline]
- Arom KV, Nicoloff DM, Kersten TE, et al. Ten years experience with the St Jude medical valve prosthesis Ann Thorac Surg 1989;47:831-837.[Abstract/Free Full Text]
- Nicoloff DM, Friedberg HD, Villafana MA. Is low-intensity anticoagulant therapy possible with an open pivot valve. Analysis of its development. Artif Organs 2002;26:438-443.[Medline]
- Gillinov AM, Blackstone EH, Alster MS, et al. The Carbomedics Top Hat supraannular aortic valve: a multicenter study Ann Thorac Surg 2003;72:1175-1180.
- Kalke BR, Desai JM, Magotra R. Mitral valve surgery in children J Thorac Cardiovasc Surg 1989;98:994-998.[Abstract]
- Lillehei CW, Nakib A, Kaster RL, Kalke BR, Rees JR. The origin and development of three new mechanical valve designs: toroidal disc, pivotal disc, and rigid bileaflet cardiac prostheses Ann Thorac Surg 1989;48(Suppl):35-37.
- Emery RW, Krogh CC, Arom KV, et al. The St. Jude Medical cardiac valve prosthesis: a 25-year experience with single valve replacement Ann Thorac Surg 2005;79:776-783.[Abstract/Free Full Text]
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Introduction
From Mumbai to Minneapolis
