Mending hearts

It has been almost five decades since Andreas Grüntzig revolutionised the world of cardiology by first successful balloon angioplasty of the proximal left anterior descending artery. The history of structural heart interventions however surprisingly predate this remarkable event. The first percutaneous closure of atrial septal defect was done in 1974, whereas the first balloon mitral valvulotomy was performed in 1984. The idea that a structural defect in the heart could be accessed with minimally invasive interventions and repaired without the trauma of an open-heart surgery with much lesser bleeding, shorter recovery time and improved postoperative pain was an intriguing and delighting one. Although cardiac surgery often remains the standard of care for these defects, in some selected anomalies, minimally invasive interventions are at par or have even eclipsed surgical procedures. Many patients have risk factors that render them ineligible for surgery, where transcatheter interventions remain a viable alternative. Within the past two decades, we have witnessed an exponential growth of novel percutaneous transcatheter therapies for the treatment of valvular and congenital heart disorders.

Transcatheter aortic valve replacement (TAVR) emerged around 20 years ago and has changed the landscape of structural interventions. With time, it has evolved into a safe and effective procedure for the treatment of severe symptomatic aortic stenosis (AS) in all adults regardless of their estimated surgical risk. Surgical aortic valve replacement (SAVR) has been the traditional treatment for severe symptomatic AS, and it has been shown to improve symptoms, quality of life and survival. However, 30%–40% of patients are deemed unsuitable for SAVR because of multiple comorbidities, which increase their periprocedural mortality risk. In 2011, PARTNER B (Placement of Aortic Transcatheter Valve Trial) used SAPIEN heart valve in patients with prohibitive surgical risk. The group that received TAVR had significantly reduced all-cause mortality, repeat hospitalisation for valve or procedure-related complications except higher risk of stroke and major vascular events. PARTNER A trial compared the results of TAVR vs SAVR in high-risk surgical candidates. TAVR was associated with similar all-cause mortality compared with SAVR at 1 year. Five-year outcomes of this trial published in 2015 continued to show no mortality benefit between TAVR and SAVR. Simultaneously, 5-year outcomes of the self-expanding Medtronic ‘Core Valve’ in similar high-risk patients demonstrated similar survival rates and stroke rates and increased rates of aortic regurgitation (AR) when compared with SAVR. The patients with intermediate surgical risk were then studied with the SAPIENS XT valve in the PARTNER 2 trial and the ‘Core Valve’ in the SURTAVI trial. In both studies, TAVR was shown to be noninferior to SAVR with respect to all-cause mortality and disabling strokes. At 5-year follow-up of PARTNER 2 trial (published in 2020), primary end point was maintained, although there was higher rate of paravalvular leak in the TAVR arm. Subsequently, ‘SAPIEN 3’ and ‘Evolut’ valves were designed to minimise the AR with the use of a sealing skirt. These newer generation valves were used in the PARTNER 3 trial and Medtronic Evolut trial in 2019, which found that even in low-risk patients, TAVR had definite beneficial effect on the composite outcome of death, stroke and rehospitalisation at 1 year. TAVR also resulted in a lower risk of stroke and shorter hospital stay. Based on the PARTNER 3 and Medtronic trial results, the US Food and Drug Administration (FDA) has expanded the TAVR indication to include low surgical risk patients as well, although data on the long-term outcomes with the SAPIEN 3 or Evolut valves are not available.

The mortality rate for TAVR is lower than that for SAVR. TAVR is also associated with a lower risk of stroke, major bleeding and atrial fibrillation, as well as a shorter hospital length of stay, less pain and more rapid return to normal activities.¹ Although when compared with SAVR, TAVR resulted in higher rates of vascular complications, paravalvular regurgitation, permanent pacemaker implantation and valve intervention, the benefits often outweigh these disadvantages. Most trials with TAVR had a mean age of mid-70s with very few patients aged <65 years, so the evidence base cannot be extrapolated to these patients. Also, in younger patients, the durability of the valve is a major concern as maximum available follow-up is just 5–6 years, so it cannot be presently recommended to patients below 65 years of age. Although numerous valves are available in the market, FDA has approved only three companies, namely, Edwards Lifesciences (SAPIEN, SAPIEN XT, SAPIEN 3 and SAPIEN 3 Ultra), Medtronic (Core Valve, Evolut R, Evolut PRO, Evolut PRO+) and Boston Scientific (LOTUS Edge). The SAPIEN valve has been discontinued, and the ‘Core Valve’ is in the process of being gradually phased out. One indigenous valve—‘MyVal’—has made a significant impact in the Indian market by virtue of its design, advanced delivery system and lower cost. Our own experience has shown that TAVR can be performed safely under conscious sedation with excellent postoperative gradient reduction across the valve, minimal para valvular leak (especially with skirted valves), acceptable rates of patient prosthetic mismatch, early ambulation and discharge and low perioperative mortality rates.² Recently specialised dedicated valves have been made for the treatment of pure native AR such as the Jena valve and the J. Valve (JC Medical). Also, certain nondedicated valves such as the Core Valve, Evolut R (Medtronic), SAPIEN 3, Lotus valve and ACURATE neo (Boston Scientific) have been applied successfully in severe AR.

Mitral regurgitation (MR) is one of the most frequently encountered mitral valve (MV) diseases, and its prevalence increases significantly with age, with over 9% of patients aged ≥75 years having significant MR. MR can be divided into primary or degenerative MR, which is caused by structural abnormalities of the MV leaflets or chordae, and secondary or functional MR, which results from abnormalities of the papillary muscles, left ventricle (LV) or MV annulus. Older symptomatic patients with severe MR and reduced LV function with significant comorbidities are often considered inoperable due to high perioperative mortality.

It was in these patients that percutaneous intervention on the MV has been introduced as an alternative option. MitraClip (Abbott Laboratories Inc, Chicago, IL, USA) is one such percutaneous device approved by the FDA for use in patients with MR grade ≥3+ and a high risk of undergoing MV surgery. Till now, more than 80,000 patients in more than 50 countries have undergone the MitraClip procedure. This device uses the Alfieri edge-to-edge (E-to-E) technique, which was first introduced in the early 1990s to approximate the free edges of the mitral leaflets correcting MR without producing stenosis. MitraClip was thus designed as a grasping device delivered through the percutaneous technique. It grasps and brings together the noncoapting edges of the mitral leaflet at the site of the MR, thereby obliterating the regurgitation, converting a single large orifice into two smaller orifices. Endovascular Valve Edge-to-Edge Repair Study II trial suggested no difference in mortality or severity of MR at 5-year follow-up. MitraClip has been subsequently extensively evaluated in MITRA-FR and COAPT trials. These were randomised controlled trials and included patients with heart failure, reduced ejection fraction and moderate-to-severe secondary MR who received guideline-directed medical treatment with or without MitraClip implantation. The MITRA-FR trial did not show a significant difference in the composite primary end point of all-cause death and unplanned hospitalisation for heart failure at 12 months. In contrast, the COAPT trial showed that the primary end point of all hospitalisations for heart failure within 24 months was significantly lower in the device group than in the control group. The contrasting difference of results in these two trials can be appreciated in its details. First, the COAPT trial was a much more robust study with a central inclusion committee, larger (almost double) sample size, detailed follow-up with echocardiography and functional studies (e.g., 6-minute walk test) and a requirement for stable doses of Guideline Determined Medical Therapy (GDMT) before enrolment, compared with the MITRA-FR. The differences were also apparent in the severity of MR, degree of LV dilatation and accompanying parameters of right heart function. At enrolment, the patients in COAPT trial demonstrated greater severity of MR and less LV dilatation. In fact, the differences between the two trials can be taken for guidance regarding patient selection parameters for an optimum postdevice result. The 2020 American College of Cardiology/American Heart Association guidelines for the management of patients with valvular heart disease recommend the MitraClip in treating severely symptomatic patients with MR who are at high or prohibitive surgical risk.³ Asians have been found to have smaller left atria compared with the Western population. This smaller space makes manoeuvring and device implantation more challenging. Indian data regarding the usage of MitraClip are in its nascent stage and only limited to case reports and series.

Tricuspid valve is usually a forgotten valve and severe tricuspid regurgitation (TR) is often given a less than due importance and treatment. Functional TR is the most common form of TR and accounts for more than 90% of the cases and is usually secondary to either a left-sided heart failure or atrial fibrillation (AF) and is associated with significant morbidity and mortality. Annular dilation due to RV-free wall dilation is its most common aetiology, and classically, surgical repair or valve replacement was the only therapeutic option available. However, these are associated with up to 10% postprocedural mortality. If the patient is deemed inoperable or at high surgical risk, it has been demonstrated that transcatheter TV interventions were associated with a lower all-cause mortality and rehospitalisation when compared with optimal medical therapy alone.⁴ Several devices have been developed with different mechanisms of action. They are classified as annuloplasty devices, replacement devices, caval valve implantation and coaptation devices. Currently, selecting the appropriate technique and device can be difficult because there are several devices available in the market. If the valve anatomy is suitable, MitraClip, the FORMA repair system and the PASCAL system can be tried. Percutaneous TV replacement may be an option in some cases with too dilated a right ventricle or destroyed valvular tissues. Heterotopic caval valve implantation aims to mitigate systemic congestion by implanting balloon-expandable or self-expandable valves in the vena cavae (inferior or in combination with the superior vena cava (SVC)) with the main purpose of abolishing systolic caval backflow. The short-term and mid-term data on the safety and efficacy of various transcatheter TV therapies are encouraging. Appropriate patient selection, proper evaluation of anatomy, device durability, safety of the procedure and optimal timing of intervention are mandatory for the success and acceptability of the procedure. India is at a nascent stage in the realm of transcatheter TV interventions, with procedures limited to odd MitraClip implantation or a caval valve implantation system implantation.

Atrial fibrillation (AF) has been associated with an increased risk of stroke with substantial morbidity and mortality, especially in the aged population. Patients in AF with increased risk for thromboembolic stroke should be treated with long-term oral anticoagulation. The majority (90%) of the thrombus resides in the left atrial appendage, and it is the most common site of intracardiac thrombi not only in patients with AF but also in patients with sinus rhythm. Thus, in a patient of nonvalvular AF who has an increased risk for stroke along with any contraindication for the use of oral anticoagulation, it is recommended to consider the interventional closure of the left atrial appendage (LAAC) [(CHA₂DS₂-VASc score ≥3), class IIb recommendation].⁵ LAAC using percutaneous, catheter-based methods was first performed in 2001. At present, percutaneous LAAC is carried out most often using the Watchman (Boston Scientific, Marlborough, MA, USA) or the Amplatzer Amulet (St. Jude Medical, Saint Paul, MN, USA) devices.

The Armed Forces Medical Services (AFMS) has taken big strides in the treatment of these structural heart problems. A robust programme of TAVR, MitraClip and others has been put in place and running well. Multiple centres are in the process of getting integrated into a national network to bring quality care to our clientele.

Minimally invasive percutaneous heart valve interventions have enabled more patients to receive treatment for severe AS and other valvular diseases. These procedures have prolonged life and reduced symptoms for many patients who were previously considered unsuitable for surgery. The success of such interventions relies on the open collaboration between the surgeons, cardiologists and the anaesthetists, which comprise the heart team.