Introduction

Valvular Heart Disease (VHD) comprises rheumatic heart disease, calcific aortic valve disease, and degenerative mitral valve disease. It affects more than 75 million people worldwide and accounted for over 573,000 or 2.9 % of deaths from Cardiovascular disease according to the latest Global Burden of Cardiovascular Diseases and Risks study, 2022. ^, Rising concern due to the strong association between VHD and the rapid aging of populations worldwide has led to VHD being described as the ‘next cardiac epidemic’. Rheumatic Heart disease remains the most common VHD however calcific aortic valve stenosis is a concern with a prevalence of 9 million worldwide and symptomatic patients facing a mortality rate of about 25 % per year. Congenital heart defects, of which bicuspid aortic valves are the most common, found in approximately 0.5–0.8 % of the global population, are a major indication for early aortic valve surgery after developing symptoms secondary to regurgitation or stenosis. The limited access to VHD diagnostic techniques likely results in a significant underreporting of aortic valve stenosis and congenital heart defects, especially in low- or middle-income/resource-poor countries like Pakistan, despite it having one the greatest burdens of VHD in Asia.

Surgical Aortic Valve Replacement

Aortic valve replacement (AVR) is the most effective treatment for severe Aortic Stenosis and regurgitation. Surgical aortic valve replacement (SAVR) works by removing the native aortic valve and implanting a prosthesis of appropriate size based on the patient’s body surface area. SAVR is indicated for symptomatic patients with aortic regurgitation, aortic stenosis, bicuspid aortic valves, and Left Ventricular Outflow Tract calcification. The process is done on-pump (a heart-lung machine takes over for your heart and lungs during your surgery) and under general anesthesia via median sternotomy where the diseased valve is removed and a new valve is implanted. Mandatory transesophageal echo [TOE] is performed after weaning off of bypass to confirm the patency of the valve and proper placement, after which the incision is closed. For over 50 years, this treatment has been the gold standard due to significant improvement in symptoms with operative death rates as low as 0.5-1 %, and favorable long-term outcomes in patients with longer life expectancy. Common risks associated with SAVR are bleeding and infection and it is an invasive procedure with long recovery time. Patients who have received a mechanical valve require anticoagulation therapy for a lifetime.

Transcatheter Aortic Valve Implantation

For patients deemed inoperable or at high risk for SAVR, transcatheter aortic valve replacement (TAVR) or implantation (TAVI) has become a highly recognized treatment option. Somewhat similar to placing a stent in an artery, the TAVI approach delivers a fully collapsible replacement valve to the valve site through a catheter which when expanded pushes the old valve leaflets out of the way, and the tissue in the replacement valve takes over the job of regulating blood flow. This procedure is available for people with symptomatic severe aortic stenosis who are at low, intermediate, or high risk for standard valve replacement surgery. Current American and European guidelines share similar details on candidates for TAVI with only a minor patient age difference. Patients at high risk or deemed non-operable are considered for TAVI aged > 65- 75 and TAVI is the only option for patients aged >75-80 years. In general, patients with the Society of Thoracic Surgeons (STS) risk stratification model score of >10 % or EuroSCORE of >20 % are considered to be high risk. In the PARTNER trial which consisted of high-risk SAVR-eligible patients, the 30-day all-cause mortality was 3.4 % in the TAVI group vs. 6.5 % in the AVR group [P=0.07]. The 1-year all-cause mortality was 24.2 % in the TAVI group and 26.8 % in the AVR group respectively [P=0.44]. These data suggest that TAVI at least provides comparable benefits in high-risk patients compared to AVR and is a reasonable alternative treatment to AVR in high-risk patients particularly those with advanced age >80 years. However, in younger (particularly <65 years) high-risk patients, SAVR may be preferred given the limited evidence on the durability of TAVI beyond 5 years, high incidence of paravalvular leaks, patients with complex aortic root anatomy as well as those who require concomitant surgical procedures. ^, Adverse effects of TAVI include acute myocardial infarction, cardiac tamponade, valve embolization, device landing zone rupture, and coronary artery blockage as peri-procedural consequences. Vascular access/bleeding, mechanical valve problems, electrical conduction abnormalities, and end-organ damage are complications that can arise after the procedure.

Uptake in Pakistan

Pakistan was not the first to follow their European and US counterparts in including TAVI into their regime for high-risk patients, who are otherwise left on medical management due to high-risk or ineligibility for operation. In Asia, Singapore started the TAVI program in 2009 and in the Middle East, Turkey was the first country to start the TAVI program followed by Iran and Saudi Arabia in 2010. Pakistan’s largest Cardiovascular institute, the National Institute of Cardiovascular Diseases (NICVD) performed its very first TAVI in 2015 with the support of foreign doctors and was the first to develop a structured TAVI program, which now runs independently. Renowned cardiovascular institutes such as The Aga Khan University Hospital performed their first TAVI in 2018, Shifa International performed its first TAVI procedure in 2020 and Peshawar Institute of Cardiology performed its first TAVI in 2022. TAVI has been proven as the treatment of choice for high-risk or inoperable patients, but the costs are extensive when compared to standard SAVR. The TAVI implant kit alone (valve, balloon, sheath) has a cost of $32,500, while the surgical valve cost is only $5,000, which in Pakistani rupees amounts to approximately PKR 9 million and 1.4 million respectively, a difference of almost 85 %. According to the WHO-CHOICE (World Health Organization-CHOosing Interventions that are Cost-Effective) project, interventions are highly cost-effective when they have incremental cost-effectiveness ratio (ICER) below the gross domestic product (GDP) per capita and not cost-effective when the ICER is >3 times the GDP per capita. Pakistan as a lower middle-income country has a GDP that is only 10 % of the ICER for TAVI. Pakistan also bears the brunt of low healthcare expenditure, with only 2.9 % being spent on healthcare according to the latest World Bank data, compared to 5 % proposed by the World Health Organization. The costs involved make the procedure very difficult to bring to a routine level, and the dedicated space and human resources required to perform this procedure in Pakistan fall short of the demand. NICVD, which is the only government-level structured TAVI program in Karachi, caters to a population of more than 20 million, with more influx from rural areas, leading to prolonged waiting times to receive treatment. ^, Due to the costs involved, even trained doctors are unable to perform the surgery due to extensive out-of-pocket payments required, unable to be met by patients in a country where now 40 % of people live below the poverty line. Furthermore, recent demographic studies of the elderly state that the 6 % of the population of Pakistan that is over the age of 60 is on the verge of rising rapidly due to reduced mortality, projected to increase to 12.4 % or approximately 43 million people by 2050. With predictions indicating an imminent rise in high-risk patients the need for TAVI will undoubtedly increase. Where on the other hand, the developed world has now been increasingly studying the effectiveness of this procedure in intermediate (STS score 4-8 %) to low-risk (STS score < 4 %) patients with promising results, ^{, ,} in Pakistan, intermediate to low-risk populations in most cases must be treated with SAVR and are unfortunately not offered TAVI but to high-risk patients due to priority. Adding to this, Pakistan faces a shortage of both general and specialized interventional cardiologists (1.12 physicians per 1000 people), and there are only 11 accredited interventional cardiology fellowship programs (0.08 per million adult population). The lack of formally trained interventional cardiologists as well as necessary technological advancements such as cardiac device support, electrophysiology procedures, and advanced cardiac imaging required for the success of this procedure has led to very limited uptake of the TAVI procedure in Pakistan. The deficiency of cardiovascular fellowship programs within Pakistan leads to many medical graduates who intend to specialize in minimally invasive subspecialties traveling abroad, of these doctors many do not return to serve within the Pakistani healthcare system, this exodus contributing to healthcare resource depletion via loss of talent to other countries.

The Way Ahead

Ever since the first TAVI procedure was carried out in the Netherlands in 2002, the field of transcatheter valve implantation for aortic stenosis has evolved to become a safe and advanced percutaneous approach for improved quality of life in patients at high risk for surgery or of very old age or both. It is an option that has proven to be lifesaving for those left on medicinal management, which has a 20 % higher 1-year mortality as compared to TAVI, as well as for those patients who may not be operable to begin with. It is necessary now to incorporate this approach as much as possible, with integrative heart team approaches encouraging inter-field cooperation and better, cost-effective treatment plans for patients. Because of its lower operative risk and its better hemodynamic profile, it is predicted that in the future TAVI might completely replace SAVR provided its durability remains comparable. Pakistan’s prospects with TAVI are hopeful but require a multi-disciplinary approach to one day make it a part of standard care. Structured training programs to meet the demand of increased cardiovascular disease burden and increasing risk factors such as smoking and hypertension are required, with satellite centers to cater to the rural population as well as to reduce the burden on urban setups and ensure proper follow-ups which may be otherwise neglected due to travel times and resource constraints. Funding by the government to establish programs like the successful NICVD program can and has proved paradigm-shifting in cardiovascular disease management in the country, providing cardiac care to patients to improve survival benefits. Foreign-trained cardiologists and competent program directors may be recruited as advisors for their support in the establishment of and supervision of new programs to make them viable for the foreseeable future until locally trained doctors take the baton, increasing both self-dependency of the country and employment opportunities for locally trained interventional cardiologists. The future of TAVI in Pakistan depends highly on decisions to be made by the concerned boards and government entities to prioritize its immediate inclusion into a standard protocol for high-risk and inoperable patients. Evaluation of its cost-effectiveness will be paramount to its integration into VHD management in Pakistan. Large-scale multi-center trials for TAVI to cater to Pakistan’s demographics in particular and collaboration with valve suppliers for subsidized rates will be a start to the process.

Contributors statement

Muddassir Syed Saleem: Bringing up the concept of the study, drafting of the work, final approval and agreeing to the accuracy of the work, also reviewed and revised the manuscript.

Nidal Bin Kamran:Drafting of the work, final approval and agreeing to the accuracy of the work.

Hafsa Kaleem: Drafting of the work, final approval and agreeing to the accuracy of the work.

Assistance with the study

none

Financial support and sponsorship

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