In India, as is happening world wide, the use of coronary interventions is likely to maintain the pace of growth seen in the past decade. This will be facilitated by better access to experienced cardiologists and catheterisation laboratories across the country. Similar growth has occurred in cardiovascular surgery despite constraints of infrastructure and affordability. Cardiovascular research established four decades ago is being carried forward with provision of indigenous technology equal to the best in the world, but tailored to local need and affordability.
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India is home to a quarter of the world’s coronary heart disease burden besides having a substantial residual prevalence of pre-transitional cardiovascular diseases (CVDs) like rheumatic fever/rheumatic heart disease.1 CVD is the greatest cause of mortality in adults in India now and an important cause of morbidity and economic loss.2–4 While prevention is the key long-term measure for curtailing such a large burden, clearly the therapeutic armamentarium needs to be as strong to provide relief for those who already have CVDs. Traditionally, the state-run health infrastructure has had few provisions to tackle chronic or acute CVD. This, however, has been changing; with the increasing requirements for cardiovascular procedures and operations, the government and private healthcare sector has grown in response to these new demands.3 This article will attempt to outline the current status of interventional cardiology and cardiovascular surgery in India.
INTERVENTIONAL CARDIOLOGY IN INDIA
The field of interventional cardiology has witnessed rapid progress in the past three decades. This has been true not just for coronary heart disease, but also non-coronary interventions in the field of heart failure, valvular and congenital heart disease, arrhythmias and electrophysiology. Whereas a decade ago India was lagging behind the West in production and consumption of these new technologies, the situation is entirely different today.
Coronary heart disease
Coronary angioplasty came to India in 1986 and coronary stenting was first performed in 1991. Since then the number of catheterisation laboratories, personnel and the volumes and complexity of cases attempted have grown rapidly.5–7 Figure 1 details the number of coronary interventions reported to Cardiological Society of India in its national registry. The actual numbers are likely to be higher as not all cardiologists have reported their data in this voluntary registry. From 2002 to 2005, the number of coronary interventions (from ∼23 000 to ∼42 100) and stent implantations (from 32 700 to 67 000) has doubled. The data provided by the industry is even higher with reportedly ∼56 000 angioplasties performed in 2005. The number of centres carrying out these procedures has also increased from 40 in 1994 to 140 by 2005. No doubt this growth has been due to advanced hardware and technology available to an interventional cardiologist today, with less reliance on on-site availability of surgical backup. Interestingly, more than half (53%) of stents implanted in 2005 were drug eluting, a number that may now have fallen, with the recent controversies about subacute thrombosis and management of stable chronic coronary artery disease. The requirement in future is going to be even higher, as it is estimated that about 3 million acute coronary events occur in India every year, and ∼1.5 million mortalities occur annually owing to these events.8 In the CREATE Registry, a multicentre study at 89 secondary and tertiary centres in 57 Indian cities for acute coronary syndrome practices, 30-day mortality rates was 7.9%, re-infarction 2.2%,9 and the overall rates of percutaneous coronary intervention 5.5% (11% in tertiary centres).9 On the other hand, the reality is that despite the presence of several large centres in big cities, most Indians do not have access to cardiac catheterisation (fig 2). This is changing, however, and many catheterisation laboratories are being set up in smaller cities.
Realising this potential, the India device market has also witnessed a boom with many stents being available today. Thus more than 15 different brands of drug-eluting stents (DES) are available in India today, with some of these stents not having any efficacy/safety data or even approval in their country of production.10 This is because unlike the USA or Europe, there is no specific organisation looking into the regulatory approval of devices in India. In the absence of any regulatory framework, this function is carried out by the Drug Controller General of India (DCGI) at present. With the recent spate of controversies surrounding the use of DES, however, a panel has been appointed by the DCGI to look into the topic. In a recent nationwide survey, members of the Cardiological Society of India were sent a questionnaire about their attitudes and practices for DES.11 Of 2590 cardiologists mailed, 16% responded, 44% of whom were active interventional cardiologists. General usage of all available stents was approved by only 1% of respondents. Twenty-six per cent agreed to usage of FDA or CE approved stents without any further scrutiny, while 66% felt that an indigenous regulatory board should be instituted and only stents approved by them should be used.
Over the past decade, we have witnessed increasing commitment of Indian companies to indigenous research and development for medical devices, especially stents. In 1996, two indigenous metallic coil stents were developed in India, one by the author (BB)12 and another at the Defence Research Laboratories, Hyderbabad (the Kalam–Raju stent).13 No major clinical trials were performed with these stents and they gradually disappeared from use like other coil stent designs. Subsequently, slotted tube stents were developed by collaboration of the All India Institute of Medical Sciences, New Delhi and Care Hospitals, Hyderabad with the medical industry. Three indigenous stents were available, Matrix (Sahajanand Medicals, Surat, India), Prostent (Vascular Concepts, Bangalore, India) and Legend (Relisys, Hyderabad, India). These stents are cost effective and are even exported, but have not been investigated in randomised clinical trials. After their inception in 2002, DES (Cypher and Taxus) were soon available in India. The high cost of these DES in India motivated the local industry to use the existing infrastructure and expertise to develop local alternatives. Three indigenous DES were made available: Infinnium (Sahajanand Medicals, Surat, India), Pronova (Vascular Concepts, Bangalore, India) and Release-T (Relisys, Hyderabad, India). All these stents have now undergone single or multicentre studies14–16 and there are plans for randomised controlled trials against the first-generation DES (Cypher, Taxus). Sahajanand Medicals has also developed a sirolimus coated stent on their Matrix platform, Supralimus, and it has undergone extensive animal and human evaluation at the Sri Chitra Institute, Trivandrum and at the All India Institute of Medical Sciences, New Delhi.17 Problems with the earlier DES including late stent thrombosis led us to develop non-polymeric nanocarbon coated DES with drug coated directly onto the nanocarbon film. Subsequently, the first animal evaluation of this paclitaxel-coated nanocarbon stent was carried out and showed excellent results.18 This led to the start of the first Indian investigator-driven multicentric clinical trial on this nanocarbon coated non-polymeric stent study (Corel-C Study approved by the DCGI, Government of India). The cost of this stent is less than half that of the international medicated stents.
With ready access to a large number of trained cardiologists, academic institutions, and a growing population potentially targeted for coronary interventions, India is also becoming a destination for international clinical research, especially for the newer stents. Thus several trials are being carried out and registries set up at multiple centres.10
Non-coronary interventions for valvular and congenital heart diseases are equally important in a country like India owing to its large population and high prevalence of rheumatic heart disease. Indian researchers have contributed significantly to the science and evidence base for percutaneous balloon mitral valvuloplasty/percutaneous transvenous mitral commissurotomy as the preferred procedure for treatment of rheumatic mitral stenosis.19 20 Close to 8000 percutaneous transvenous mitral commissurotomies were carried out in India in 2005 (fig 3) across 71 centres. Higher expertise with the procedure and the safe reuse of the expensive Inoue balloon21 has resulted in this procedure being offered to most patients with severe mitral stenosis, even those with traditionally “unsuitable morphology”, at a fraction of the cost for undergoing open mitral commissurotomy or valve replacement. Overall mortality for this procedure in 2005 was 0.2% while 1.4% required mitral valve replacement. Similarly, rheumatic tricuspid stenosis is being safely treated with balloon valvuloplasty. Declining incidence has meant that only 45 such procedures were done in 2005 as compared with 62 in 2002, with no complications reported. Aortic valve balloon dilatation (AVBD) for severe aortic stenosis was done at 32 centres in India, mostly for bicuspid aortic valve as the results for aortic stenosis of rheumatic aetiology have not been encouraging. Close to 500 pulmonary valve balloon dilatations (PVBDs) were also carried out at 42 centres in India in 2005 (fig 3), one of the most successful and safe procedures in interventional cardiology. Indian researchers have also taken part in international studies investigating the feasibility of percutaneous valve replacement.
Interventions for congenital heart diseases too are increasingly becoming common. Figure 4 shows the trends in interventions for congenital heart diseases in India. Percutaneous closure of patent ductus arteriosus (PDA) was done in more than 1000 patients at 46 centres in 2005. Over half of these were with coils, a less expensive option than with PDA closure devices. There is increasing trend for percutaneous atrial septal defect closure as well, though the high cost of the devices is still a concern. Ventricular septal defect closures are also being done in more than 15 centres across India, though the overall numbers are much less, reflecting the trend world wide. Again the numbers of dilations for coarctation of the aorta have remained static over the years; however, there is increasing use of stents with 21% of all patients with coarctation of the aorta undergoing stenting in 2005. Several other interventional procedures like balloon atrial septostomy, coil embolisation of aortopulmonary collateral arteries, inferior vena cava filter insertion, and pulmonary artery angioplasty are carried out routinely in tertiary centres in India. With widespread surgical procedures, interventional cardiology is also proving useful in dealing with certain postoperative conditions like blocked aortopulmonary shunts, conduit obstruction, residual ventricular septal defects, etc. Newer procedures like PDA stenting and atrial septal stenting are also being done in some Indian centres.
Electrophysiology and arrhythmic devices
History of pacemaker implantation started in the late 1960s in India. The first indigenous temporary pacemaker and defibrillator were developed in 1970s by eminent Indian cardiologist Professor Khalillulah, at GB Pant Hospital, New Delhi along with Mendez, an engineer entrepreneur.25 Subsequently, the early 1990s saw the development and implantation of the first indigenous permanent pacemaker. It was developed by Sri Pacetronix, who are still the only Indian company making pacemakers. In 2002, more than 8000 pacemakers were implanted across India and industry sources put the number at about 12 000 for 2006.
The first implantable cardioverter-defibrillator (ICD) implanted in India was in 1995. In 2002 more than 60 ICDs were implanted; however, since then the numbers have increased considerably. With increasing evidence base and advances in technology, biventricular pacing and defibrillator pacing combo devices are being implanted increasingly and India is no exception to this. Although there are no registries for pacemaker and other arrhythmia devices, according to industry resources, more than 12 000 conventional pacemakers, 450 ICDs, 400 cardiac resynchronisation therapy devices, and 80 combination defibrillator- resynchronisation therapy devices were implanted in India in 2006.
Invasive electrophysiology took a new turn in India with the first direct current ablation performed in 1988 and this was followed soon after by radiofrequency ablation. Today, more than 40 government and private centres in India offer radiofrequency ablation for a variety of tachyarrhythmias. As compared with 800 ablations in 1995, today more than 3000 ablations are performed in India, including their use for new indications such as atrial fibrillation.26 Important research related to atrial fibrillation in rheumatic heart disease and its control has been conducted in the country.27
The future seems to be exciting and promising for interventional cardiology, and this is true not just for coronary interventions. As is happening world wide, the use of coronary and other non-coronary interventions are likely to maintain the pace of growth seen in the past decade. This will be facilitated by better access to experienced cardiologists and catheterisation laboratories across the country. The legacy of cardiovascular research established four decades ago with the first high-altitude catheterisation laboratory,28 is being carried forward with provision of indigenous technology equal to the best in world, but tailored to local need and affordability.
CARDIOVASCULAR SURGERY IN INDIA
Heart surgery in India has grown at a steady pace and has paralleled the growing incidence of cardiovascular diseases and an increase in the number of diagnostic and interventional procedures. In the 1960s and 1970s, facilities for open heart surgery were limited to a few centres in the southern part of India and cardiothoracic and vascular surgery practice consisted primarily of thoracic operations and closed mitral valvotomies. Since then, however, the growth has been phenomenal and there are now fully equipped centres in all parts of India which offer surgery for almost all types of diseases affecting the heart. Presently more than 60 000 open heart operations are performed annually in India and most of these procedures are for coronary and valvular heart disease.29 About 5000 operations are performed annually for congenital heart disease in a few centres. Table 1 lists the leading public centres performing more than 500 open heart operations annually in India. This list is by no means exhaustive and a great number of private institutions perform a large number of procedures. Notable among these are Escorts Heart Institute and Research Centre, New Delhi, Narayana Hriduyalya, Bangalore Madras Medical Mission, Chennai and Amrita Institute of Medical Sciences, Cochin. Our centre, the All India Institute of Medical Sciences (AIIMS) is an apex tertiary level referral centre and caters to a large majority of the population from not only India but also from the surrounding countries. Table 2 shows the trend in the number of surgical procedures performed at our centre in the past few years. Table 3 shows the spectrum of surgeries performed at the AIIMS annually; other large centres in India have a similar profile, though the numbers would be smaller than at the AIIMS. The miscellaneous group in table 3 consists of the most complex neonatal repairs of truncus arteriosus, anomalous origin of the left coronary artery from the pulmonary artery, interrupted aortic arch, etc.
The detailed report of the National Cardiac Surgical Registry (2004)30 was published in the year 2006 (data contributed by 14 centres across India). Fourteen centres in India contributed data for this registry. More and more centres are now contributing their data to this registry. An analysis of the registry data shows that nearly 70% of the operated patients were male. Female patients comprised almost 40% of the patients undergoing surgery for valvular and congenital heart disease, but only 12% of operations for ischaemic heart disease. Of all the procedures performed, 39% were for ischaemic heart disease, 35% were for congenital heart disease, 25% were for valvular heart disease and 1% were for other diseases. Nearly 44% of isolated coronary artery bypass grafting (CABG) procedures were performed without the use of cardiopulmonary bypass. Re-operations comprised <1% cases. It was felt that there was a need to develop a standard nomenclature system to correctly categorise the surgical procedures like the Society of Thoracic Surgeons, US database and to encourage more centres to participate more actively in developing this database.
Status and problems of heart surgery in India
Most of the centres performing open heart surgery are located in the major cities and patients have to travel long distances for treatment. The current state of heart surgery in India and the problems faced are similar to those in any developing country.31 There are problems of logistics and developing an infrastructure at every step, thus surgeons have evolved indigenous techniques and improvisations. Many times they have to use resterilised equipment to cut down the costs. Also, there are limited facilities for state-of-the art paediatric cardiac surgery and postoperative care in India and fewer than 15 hospitals are equipped to carry out complex neonatal and infant heart surgery.32 In a large majority of the centres paediatric cardiac care derives funds from a busy adult programme. Most of the cardiac centres prefer to invest time, money and manpower in the treatment of adults with coronary artery disease since it is lucrative and financially viable.33 The pharmaceutical industry shows little interest in the development of a paediatric cardiology infrastructure. At present, paediatric cardiac care is provided by a few government institutions and mostly by private, semiprivate and charitable institutions. These institutions can cater only for a tiny fraction of the affected population.
Performing operations free of cost is not a viable proposition in the long run as the invested resources rapidly become exhausted and programmes run the risk of cutting down their work or even closing down. The cost of the most commonly performed procedures (atrial septal defect, ventricular septal defect, and tetralogy of Fallot) at most centres exceeds the annual family income of a vast majority of the Indian population. In the absence of state health insurance, the cost burden has to be borne by the government/charitable organisations or, mostly, by the patients themselves. Often the parents of a child with congenital heart disease prefer not to seek surgery for their critically ill child but prefer to have another child rather than resort to desperate measures to generate the necessary finances, especially when the children are female.30 34
Coronary artery surgery
At present, coronary artery surgery is the most common cardiac operation performed in India. A large majority of these procedures are performed without the use of cardiopulmonary bypass and gratifying results have been reported. There has recently been interest in performing these procedures with robotic assistance35 and facilities for this are available at our institution and at Escorts Heart Institute, New Delhi and at Care hospital, Hyderabad.
Valvular heart surgery
Valvular heart surgery is the second most common cardiac operation in India owing to a large population of patients with rheumatic heart disease. We believe that it is better to perform valve reconstruction rather than replacement wherever feasible at it avoids the hazards of long-term anticoagulation, preserves ventricular function, improves survival and is more cost effective and improves the quality of life, particularly in young patients.36 Many of the techniques developed for valve repair are indigenous and good results have been obtained and detailed follow-up has been reported. Similarly, a homograft valve bank has been established at our centre and at a few other centres and techniques for homograft valve implantation and the Ross procedure have been practised with good results.37–39 At the Sree Chitra Institute of Medical Sciences, Trivendrum, the TTK-Chitra valve was designed and it is produced in India much more cheaply than the currently available heart valve substitutes; good results have been reported.40
Congenital heart surgery
As detailed above, complex congenital heart surgery is performed at only a few selected centres. However, at centres where it is practised, nearly all procedures are carried out and good early and long-term results have been reported. Indigenous techniques of pulmonary artery banding for sick neonates have cut down the costs tremendously.41 Circuits for modified ultrafiltration have been developed42 and indigenous techniques of off-pump superior-cavopulmonary anastomosis have cut down the costs and improved results (Talwar S, Choudhary SK. Oral presentation at 8th annual conference of the Pediatric Cardiac Society of India, 2006).
The first successful human heart transplant in India was carried out at AIIMS, New Delhi in 1994. Since then 22 patients have undergone cardiac transplant: 20 of these had dilated cardiomyopathy and two had ischaemic cardiomyopathy. Their ages ranged from 19 to 52 years. There were two early deaths. The follow-up has ranged from 1 month to 125 months with more than 5 years’ follow-up in five patients. One death occurred owing to late rejection. The problems we encountered were donor organ scarcity and for patients who had received a transplant, infection was the major factor responsible for morbidity and mortality. Overall, about 40 cardiac transplants have been performed in India, including those at AIIMS.
Stem cell transplantation
There has been growing interest in stem cell transfer as a method of improving prognosis of heart failure. At our hospital, we use autologous bone marrow cells for this purpose. Patients with coronary artery disease undergoing CABG who have reduced LV function with an area of non-viable myocardium are considered as candidates for this procedure.
At our institute, 43 patients have undergone combined CABG and stem cell transplantation between February 2003 and October 2006.43 The mean (SD) NYHA class improved significantly from a baseline of 2.9 (0.7) to 1.25 (0.6). On echocardiography at last follow-up, the LV end-diastolic and end-systolic dimensions were found to have remained stable and the LV ejection fraction had improved in nearly 50% of the patients; none had deteriorated. On Holter evaluation at follow-up, no significant arrhythmias were noted. Therefore, bone marrow derived stem cell transplantation during CABG is feasible and safe, and the bone marrow obtained from sternum at the time of CABG provides an adequate number of stem cells. Our early data suggest that this procedure may be beneficial in patients with scars/recent infarct in the left ventricle. However, further studies are needed to confirm this. More recently, we have published the results of our study on the percutaneous use of autologous stem cells in idiopathic dilated cardiomyopathy. As far as we know, this is the first published study of its kind in this subset of patients, who are showing promise.44 For the future stem cell transfer is a promising technique in India for a large number of patients.
Cardiovascular surgery in India has grown at a steady pace and mirrors the growth world wide. The biggest problems facing a cardiovascular surgeon in India today are those of infrastructure costs and affordability of the procedure by the patient. This has not deterred the establishment of world-class cardiovascular surgery centres in India, which provide treatment to people all over the world as well as developing indigenous techniques that match the resources of the Indian population.
Competing interests: None.
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