Structural Heart 7 (2023) 100219

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Structural Heart
journal homepage: www.structuralheartjournal.org

Review Article

Rheumatic Heart Disease in the Developing World

Michael T. Simpson, MD a, Mateusz Kachel, MD a, Robert C. Neely, MD b, W. Clinton Erwin, MD a,
Aleena Yasin, MD c, Amisha Patel, MD d , Dasari Prasada Rao, MBBS, MS, MCh e,
Kaushal Pandey, MBBS, MCh f, Isaac George, MD a, *
a
Division of Cardiac, Thoracic and Vascular Surgery, Department of Surgery, Columbia University College of Physicians & Surgeons, New York, New York, USA
b
Cardiothoracic and Vascular Surgeons, Austin, Texas, USA
c
Department of Cardiothoracic Surgery, Stanford University, Palo Alto, California, USA
d
Division of Cardiology, Mount Sinai Medical Center, New York, New York, USA
e
Department of Cardiothoracic Surgery, Apollo Spectra Hospital, Hyderabad, India
f
Centre for Cardiac Care, Hinduja Hospital, Mumbai, India

A R T I C L E I N F O A B S T R A C T

Article history: Despite recent public policy initiatives, rheumatic heart disease (RHD) remains a major source of morbidity
Submitted 27 May 2022 worldwide. Rheumatic heart disease occurs as a sequela of Streptococcus pyogenes (group A streptococcal [GAS])
Revised 1 August 2023 infection in patients with genetic susceptibility. Strategies for prevention of RHD or progression of RHD include
Accepted 3 August 2023
prevention of GAS infection with community initiatives, effective treatment of GAS infection, and secondary
Available online 19 September 2023
prophylaxis with intramuscular penicillin. The cardiac surgical community has attempted to improve the avail-
Guest Editor: Zoltan Turi, MD
ability of surgery in RHD-endemic areas with some success, and operative techniques and outcomes of valve
Keywords: repair continue to improve, potentially offering patients a safer, more durable operation. Innovation offers hope
Mitral valve repair for a more scalable solution with improved biomaterials and transcatheter delivery technology; however, cost
Mitral valve replacement remains a barrier.
Rheumatic heart disease

A B B R E V I A T I O N S ARF, acute rheumatic fever; BMV, balloon mitral valvuloplasty; BPG, benzathine penicillin G; CHF, congestive
heart failure; CMC, closed mitral commissurotomy; GAS, group A streptococcus; LMIC, lower- and middle-income
countries; RHD, rheumatic heart disease.

Introduction attention has rightfully been paid to screening primary and sec-
ondary prevention of RHD, there has been less focus on broadening
Rheumatic heart disease (RHD) remains an underrecognized access to cardiac care and surgical care for those patients already
health issue globally, despite initiatives introduced over the last with established RHD. In this review, we describe pathophysiology,
several decades that have helped decrease the global number of primary and secondary prophylaxis, and variety of therapies avail-
cases during this time. This is in part due to the highly effective able for RHD in developing countries.
public health policies put forth in industrialized nations in the last
half-century to prevent, recognize, and treat group A streptococcal Epidemiology
(GAS) infections. However, worldwide RHD cases number over 15
million and contribute to over two hundred thousand deaths per Endemic patterns of RHD are seen in lower- and middle-income
year.1 Progress has been made over the last 2 decades as several countries (LMIC), especially in Southeast Asia, sub-Saharan Africa, and
nations in the developing world with high disease prevalence have Oceania.1 China, India, Pakistan, and Indonesia were the countries with
prioritized its treatment and global health organizations have pur- the highest number of RHD cases in 2015; however, age-adjusted prev-
sued the elimination of RHD with renewed vigor. While significant alence and death rates are highest in Oceania, sub-Saharan Africa, and

* Address correspondence to: Isaac George, MD, Structural Heart Disease, New York-Presbyterian Hospital Milstein Hospital Building, 177 Ft. Washington Avenue,
7th Floor, Garden North, New York, NY 10032.
E-mail address: ig2006@cumc.columbia.edu (I. George).

https://doi.org/10.1016/j.shj.2023.100219
2474-8706/© 2023 The Authors. Published by Elsevier Inc. on behalf of Cardiovascular Research Foundation. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
M.T. Simpson et al. Structural Heart 7 (2023) 100219

South Asia. Notably, the worldwide prevalence of heart failure due to Economic Impact
RHD increased from 1990 to 2015 (Figure 1).1
The effects of RHD are disproportionately felt by school-aged chil-
Pathophysiology dren and young adults in their most economically productive years. The
cost of premature deaths due to RHD is estimated to be on the order of
RHD occurs as an autoimmune sequela of acute rheumatic fever trillions of US dollars annually.6 Effects on children and adolescents
(ARF), which usually occurs after GAS pharyngitis, although there is include increased school absence and rates of dropout, which have a
more recent data suggesting that GAS skin and soft tissue infection downstream impact on the ability of children to eventually support their
may play a larger role in the developing world than in industrialized own families independently. At the same time, young adults sick with
countries.2 The pathophysiology of ARF is not completely understood RHD will have decreased capacity to work, impairing their ability to
but is thought to involve cross-reactivity between GAS and host provide for themselves and their families. The impact of disability
proteins in a genetically susceptible host.2 Rheumatic fever is diag- caused by RHD accounts for nearly 0.5% of worldwide disability
nosed based on the Jones criteria, which include a combination of adjusted life years.1 Additionally, RHD affects many women of child-
major and minor clinical symptoms of ARF with or without evidence bearing age and has implications for maternal health in LMICs. Severe
of a prior GAS infection. The most common presenting symptoms are and symptomatic mitral stenosis are independent predictors of adverse
arthritis and fever; chorea may be considered pathognomonic for ARF fetal and maternal outcomes.7 Together, these effects on those who are
but occurs less frequently. Importantly, these criteria have more typically society’s most productive workers have a profound socioeco-
recently been revised to include population risk in order to increase nomic impact.
the detection of ARF in endemic areas. Importantly, there is some
suggestion that the presentation of ARF may differ between the Prevention/Primary Prophylaxis
developing world and industrialized countries; reasons for this are
unclear but may be due to decreased suspicion in industrialized na- Success in essentially eradicating RHD from the industrialized world
tions, leading to delayed diagnosis.3 was a result of a multipronged effort to improve public health infra-
While ARF symptoms resolve, damage done to valves remains and structure and access to primary care. Often overlooked in the prevention
progresses with subsequent GAS infections, leading to progressive of RHD is so-called “primordial prophylaxis”. Such social determinants of
valvular fibrosis seen in RHD. The mitral valve is most frequently health are poverty-related and include overcrowding and poor nutrition.
involved and can be affected by both mitral stenosis and regurgitation. Household crowding, defined as in-home population of greater than 2
50% to 80% of patients with carditis during an initial ARF episode will persons per habitable room8 has been shown to increase transmission of
progress to chronic RHD. GAS infection.9 Additionally, poor nutrition has been associated with
ARF primarily affects school-aged children, likely related to GAS increased susceptibility to ARF.10 These socioeconomic factors represent
transmission among students. The low incidence of ARF relative to that of potential targets for intervention for both governments and nongovern-
GAS infection is not fully explained.4 Some studies point to the possibility mental organizations.
of genetic disposition, implicating immune-related genes such as human The core of primary prevention for RHD is the effective diagnosis
leukocyte antigen, toll-like receptor, and cytokines.5 The pathophysi- and treatment of GAS infection with antimicrobial agents. Consider-
ology of RHD development is shown in Figure 2. ations here include symptom recognition, health care literacy, and

Figure 1. Global Impact of RHD. Countries with endemic patterns of RHD are commonly seen to have increasing number of cases over the previous decade; however,
cases are rising in some middle- and upper-income countries, likely as a result of recent immigration patterns.
Abbreviation: RHD, rheumatic heart disease.

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M.T. Simpson et al. Structural Heart 7 (2023) 100219

Figure 2. Pathophysiology of RHD. RHD occurs as a sequela of GAS infection, especially pharyngitis. Social determinants of health and genetic predisposition play a
role in repeated infection as well as in the progression to RHD. Cross-reactive antibodies and immune cells form in response to GAS infection and attack endothelial
cells throughout the body; however, damage to the endothelial surface of the valves is not repaired effectively.
Abbreviations: GAS, group A streptococcal; RHD, rheumatic heart disease.

willingness to present for primary care. Upon presentation, the avail- Lastly, GAS vaccine development represents a major opportunity to
ability of accurate and expedient diagnostic testing and accessibility to reduce ARF and RHD in the developing world. Vaccination for GAS has
treatment are critical factors that affect disease progression and long- been difficult for several reasons: complex epidemiology, lack of surrogate
term sequelae. As part of a comprehensive RHD program, the World markers for protection in humans, genetic diversity of the most common
Health Organzation recommends a community-based approach vaccine target, and perceived safety concerns that a vaccine could pre-
focusing on awareness of GAS and its link with RHD, and such programs cipitate ARF. Momentum toward vaccination slowed as ARF and RHD
have shown good results.11 cases plummeted in the industrialized world and investment decreased.
Microbiologic testing is the gold standard for the diagnosis of GAS However, with new data showing that indigenous populations in Australia
infection; however, access in the developing world is limited, and this and New Zealand deal with high rates of ARF, there is renewed interest.
may not be cost-effective.12 Rapid tests may be deployed in these areas Several vaccines are currently in the early stages of development.20,21
with high sensitivity and specificity.13 Clinical decision-making algo-
rithms also play a role in the developing world due to supply chain dif- Screening
ficulties in obtaining rapid tests. Clinical decision rules have been shown
in Egypt to be highly sensitive while also limiting unnecessary antibiotic Despite the proven link between ARF and RHD, it is common in the
use.14 Algorithms may be applied to other communities; however, likely developing world for RHD to present without an antecedent history of
require validation studies and modifications prior to use. ARF.22 Latency between ARF and the development of RHD may
GAS infections are exquisitely sensitive to penicillin, and a single contribute to this. The highest incidence of ARF is in children, while RHD
shot of benzathine penicillin G (BPG) administered intramuscularly presents most commonly in the third and fourth decades of life.23 This
effectively treats both pharyngitis and impetigo. Early treatment of period represents an opportunity for surveillance and identification of
GAS infections mitigates the molecular mimicry that causes ARF and early RHD as well as initiation of secondary prophylactic treatment.
has been shown to prevent up to 70% of ARF cases.15 BPG is listed as Screening for RHD has been recommended since at least the 1960s.24
a World Health Organization Essential Medication for Children.16 Broadly speaking, there are 2 types of screening for RHD used in the
Despite this, reports from providers in the developing world suggest developing world: auscultation and echocardiography. While it has
widespread BPG shortages, with some reporting no access to BPG at largely fallen out of favor in the last several decades, auscultation does
all.17 This is clearly problematic for strategies of both primary and offer the advantage of being readily available and translatable in remote
secondary prophylaxis. Problems with supply aside, BPG, when rural communities. Compared with echocardiography, however,
available, is affordable; it is sold at a median price of $0.31 per auscultation is significantly less sensitive and specific for the detection of
dose.17 Despite the low price, questions remain concerning the cost- RHD. One systematic review found that echocardiography detects
effectiveness of primary prevention as a RHD strategy at the popu- greater than 4 times the number of cases as auscultation.25 In fact, the
lation level. Data from the early 2000s reports the average per-person increase in utilization of echocardiography for the detection of RHD was
cost of microbiologic GAS infection confirmation followed by BPG an important part of the renewed interest in treating RHD as a global
administration to be $50, while the number needed to treat was 50 in scourge. It also led to the creation of a unified set of echocardiographic
order to prevent one case of ARF.15,17–19 criteria to diagnose RHD.26 Three categories of RHD were created based

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M.T. Simpson et al. Structural Heart 7 (2023) 100219

on the morphological features of the aortic and mitral valves: definite duration of secondary prophylaxis depends on the age of the most
RHD, borderline RHD, and normal. Echocardiography enabled the recent ARF episode and the presence of rheumatic valvular heart dis-
detection of previously undetected cases of borderline RHD. The natural ease as seen on echocardiography. For example, Australian guidelines
history of this category is less clear but has implications with regards to dictate that patients without evidence of carditis be treated until they
potential therapies; studies in India, Africa, and the Pacific provide evi- are 18 years old or for 5 years after the most recent ARF episode, while
dence that children diagnosed with borderline RHD27–31 have minimal those patients with severe RHD warrant prophylaxis up to the age of
disease progression at medium-term follow-up, while other studies from 40.51 Importantly, variations in national policies must also reflect the
rural Australia and Nepal showed the opposite.32,33 Another large pro- availability of resources. This includes not only the availability of BPG
spective screening program of pregnant women in India identified mul- but also the ability of a national health care system to provide
tiple at-risk women with RHD and other structural heart abnormalities comprehensive surgical and medical treatment to those patients who
and allowed for medical and procedural care of the women and fetuses in develop severe RHD. In many developing nations, it is likely more
the high-risk peripartum period. As a result, controversy exists as to cost-effective to divert resources to improve an existing secondary
whether or not to initiate secondary prophylaxis in this group. Answering prophylaxis program as opposed to trying to improve access to cardiac
this key question will be central to the continued development of RHD surgical care, at least in the short term. More data to address this
screening programs.34 important question is a research priority.
Other problems exist with the implementation of echocardiographic
screening programs. Echocardiographic screening requires equipment, Availability of Cardiac Surgery
a reliable source of electricity, as well as expertise to perform and
interpret the exam. RHD-endemic areas tend to be resource-poor and In recognition of the global problem RHD presents, cardiac surgeons
lack access to skilled health care workers. In response, initiatives to and cardiologists issued the Drakensburg declaration 15 years ago in a
train nonexpert health care workers have been implemented and have call to action for the development of prevention and screening programs
shown promise.35 Nurses attending an 8-week training course with the lofty goal of eradicating RHD. Despite this, RHD continues to be
providing echocardiographic screening were 85% specific and 84% a major challenge. Access to open heart surgery, currently the only
sensitive relative to examination by a pediatric cardiologist. Concerns definitive treatment for advanced RHD, is severely limited in the devel-
about the cost of echocardiography equipment have been addressed oping world. In 2018, there was a renewed push to increase access to
with the use of less expensive handheld echocardiography, which has cardiac surgical care globally.1,27,52 There is an estimated need to
been shown to be an effective screening tool in RHD-endemic perform 300 cardiac surgical operations per 1 million people in
regions.36–38 RHD-endemic regions of lower income countries. This is in stark contrast
to the number of available centers in sub-Saharan Africa, where 22
Secondary Prophylaxis centers serve approximately 1 billion people.
Prior efforts to increase access have focused on mission trips from
Secondary prophylaxis refers to the strategy of preventing recurrent high-income countries and training pathways to fund surgeons from
GAS infections and ARF episodes in order to limit the progression of low-income countries to train in high-income countries. Neither is
valvular disease. After an initial bout of ARF, recurrence rates may be as ideal for a number of reasons. Mission trips cannot fully fill the need
high as 50%,39 with each attack causing further valvular damage and gap as they do not provide incentives for local investment in infra-
the progression of RHD. A systematic review summarized the effects of structure or centers and fail to provide a sustainable solution. Addi-
secondary prophylaxis in preventing further ARF episodes, showing a tionally, they do not address issues with postoperative follow-up for
relative risk reduction of 55% with penicillin compared to observa- patients who undergo mitral valve repair or replacement. Funding
tion.40 Prevention of recurrent ARF has been associated with less trainees from low-income regions solves some of these issues, but may
valvular damage and mortality.41,42 BPG is the first-line antibiotic for not provide adequate exposure to pathology and operations they will
secondary prophylaxis; the recommended regimen is 1.2 million units perform in their home countries. Moreover, this option does not
every 4 weeks for a minimum of 10 years and sometimes longer.43 With provide training in the resource-limited environments that are most in
adherence to this regimen, ARF recurrence is acceptably low.44,45 need. Historically, 1 unintended consequence of such advanced
However, data indicates that patient adherence, especially in low so- training is the potential low return rate of specialists to their country
cioeconomic countries and populations, is low.46 The factors that affect of origin.53
adherence to secondary prophylactic regimens are similar to those for A more recent initiative has been to identify and invest in local cen-
primary prophylaxis. Potential areas for improvement include ters that have demonstrated the capacity to provide quality care as well
longer-lasting depot injections to allow for less frequent dosing and as quality training.54 At the same time, longer-term embedding of
mitigating the impact of low provider access, especially in remote experienced surgeons at these centers and other more fledgling centers
communities. Administration of BPG with lidocaine can improve have demonstrated a quickening of institutional learning curves. Aswan
postinjection pain. The formulation of BPG that is premixed without the Heart Center in Egypt is one such success story.55
requirement for refrigeration may also aid with distribution.47 How- The delivery of cardiac surgical care in developing nations poses
ever, there is benefit to secondary prophylaxis even without full challenges beyond the availability of surgical personnel. Prior to estab-
adherence. Current guidelines target at least 80% regimen adherence, lishing an open-heart surgery program, a full needs assessment is para-
but data indicates that benefits start as low as 40% and increase with mount to ensuring good patient outcomes. Hospital sites must be
each 10% increase.48 evaluated for energy reliability, ventilators, echocardiography, radiog-
There is also evidence that suggests that secondary prophylaxis can be raphy, functional cardiopulmonary bypass machines, ability to check
associated with regression of RHD based on echocardiographic criteria. activated clotting times, and well-stocked pharmacies and blood banks.
Several studies have reported this; however, low patient numbers pre- While some of these needs overlap significantly with other clinical areas,
clude further analysis. This is an important question to address to justify there are multiple cardiac surgery-specific fixed and variable costs that
more resources for secondary prophylaxis programs. can be cost-prohibitive without significant investment by the govern-
Some controversy exists regarding the duration of secondary pro- ment or charity.56 Essential personnel include full-time nurses with
phylaxis, as rates of GAS infection decrease substantially as patients open-heart experience, anesthesiologists, perfusionists, and critical care
enter adulthood.49,50 Data comparing the effectiveness of different providers, if available. Procuring sufficient valves, conduits, and pace-
durations of secondary prophylaxis are lacking. As a result, most na- maker implants can pose a significant logistical challenge for new pro-
tions rely on guidance from expert opinion. Generally speaking, the grams, but charity funds and donation programs are available through

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M.T. Simpson et al. Structural Heart 7 (2023) 100219

Figure 3. Valvular Pathology in RHD. The mitral valve is most commonly affected in RHD. Mitral valve lesions generally begin as predominant regurgitant lesions;
however, as valve damage progresses, stenosis occurs. The aortic and tricuspid valves can also be affected by the RHD disease process; the tricuspid valve can also be
affected as a sequelae of mitral disease and pulmonary hypertension.
Abbreviation: RHD, rheumatic heart disease.

most of the major device companies. The availability of such resources ability of open commissurotomy to also address the abovementioned
can impact patient case selection. limitations.58 Open surgery achieved a larger mitral valve area and a
There are similar infrastructural issues in terms of postoperative greater increase in cardiac index compared to CMC.59 Furthermore, it
follow-up as with screening and prophylaxis. Patients undergoing valve was reported that both the incidence of reoperation as well as
repair or bioprosthetic replacement require monitoring for repair failure valve-related morbidity and mortality were significantly lower after open
and structural valve degeneration. Mechanical valve replacement is a commissurotomy. However, long-term survival was similar for both.60
long-term solution but requires lifelong anticoagulation and periodic BMV overtook surgical commissurotomy as the first-line therapy for
blood work in order to mitigate the risk of severe bleeding or valve symptomatic mitral RHD with favorable anatomy given its
thrombosis. The management of anticoagulation in this setting is espe- equivalent-or-better success and restenosis rates and lesser invasive-
cially problematic given the prevalence of young women affected in ness.61,62 Nevertheless, CMC may still offer some utility in particularly
childbearing years. In summary, efforts to improve global access to car- resource-scarce locations.58 The above is further supported by the more
diac surgical care must address a myriad of infrastructural needs. recent study showing comparable long-term results of CMC compared
with BMV.63
Rheumatic Mitral Valve Interventions BMV optimal short- and long-term outcomes are associated with a
Wilkins score of 8 or less.57,64 In the original analysis, all patients with a
Patients with RHD should be assessed for severity of symptoms with Wilkins score greater than 11 had suboptimal outcomes, while scores
intervention based on the affected valves and specific pathology, as between 9 and 11 were not predictive of outcome. Patients with a score
summarized in Figure 3. Mitral stenosis occurs in progressive RHD and is of 9 to 11 without other risk variables such as age and New York Heart
common at the time of presentation or intervention. Once symptoms Association class IV heart failure may be considered for BMV as there is
develop, the valve should be assessed echocardiographically and a Wil- reasonable immediate success and 5-year event-free survival.57,64
kins score calculated. The Wilkins score is a semiquantitative rubric used Broadly speaking, there are 2 techniques of BMV: the double-balloon
to assess the severity of valvular disease and is correlated with the technique and the Inoue balloon technique. The Inoue balloon tech-
outcome after balloon mitral valvuloplasty (BMV). Components of the nique is widely preferred today as it has demonstrated similar efficacy
Wilkins score are leaflet mobility, leaflet thickening, subvalvar thick- with less risk of procedural complications.65
ening, and calcification.57 For those patients in whom BMV is contraindicated, including those
Closed mitral commissurotomy (CMC) was the first operation with a Wilkins score >11, grade 2 or more mitral regurgitation, extensive
described to relieve mitral stenosis in RHD. This operation requires a commissural calcification, left atrial thrombus, or other significant
thoracotomy and is traditionally done without cardiopulmonary bypass. valvular disease, surgical intervention should be recommended.66 The
The method offered a cheap and relatively safe solution to treating pa- options for surgical intervention on the mitral valve include mitral valve
tients with RHD, in which the surgeon’s finger provides both tactile repair and mitral valve replacement. Experience with degenerative mitral
assessment and guides the dilator. The main limitation of CMC was the valve disease in industrialized countries has demonstrated the superior-
presence of calcified leaflets and/or diseased subvalvular apparatus.58 It ity of valve repair; however, the complexity of valve pathology seen in
was largely replaced by open mitral commissurotomy after the devel- rheumatic mitral valve disease prevents extrapolation of this finding to
opment of cardiopulmonary bypass due to direct visualization and the the RHD population.67 Given the aforementioned issues with follow-up

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after mitral valve replacement along with the younger population pre- preferable. However, in patients for whom anticoagulation with warfarin
senting with RHD, there has been a recent effort to improve techniques is contraindicated, such as women who plan to become pregnant, bio-
for rheumatic mitral valve repair. prosthetic valve replacement is acceptable. Patients should be counseled
Mitral valve repair for RHD is not straightforward due to the that they will likely require further intervention in this case, and redo
involvement of both the leaflets and the subvalvular apparatus. The mitral valve replacement is associated with relatively high mortality.71
principles of repair are based on individual leaflet morphology and While mechanical valve replacement does offer benefits in terms of
dysfunction. Commissures are split with a knife; fused primary chords longevity, it is important to note that anticoagulation management is
are separated and debulked without causing a flail. Anterior and pos- challenging in LMICs, leading to higher rates of valve thrombosis,
terior leaflet shaving and/or elongation are also employed to increase thromboembolism, and bleeding complications than in industrialized
mobility and coaptation. If pathology affects the full thickness of the nations.72 Surgical options for rheumatic mitral valve disease are sum-
leaflet, resection may be required, followed by augmentation with marized in Figure 4.
glutaraldehyde-fixed autologous pericardium. Bulky calcification may While the mitral valve is most affected in RHD, lesions on the aortic
pose similar problems for leaflet thinning and necessitate resection.68 valve (2% isolated) and less commonly the tricuspid valve do occur.
Gortex neochords can be employed if resection of abnormal chords has Lesion severity impacts the efficacy of BMV in improving patient symp-
led to unsupported leaflet edges. Due to complexity and need for sig- toms. Concomitant lesions should therefore be addressed surgically.
nificant experience, mitral valve repair has not been widely adopted in Tricuspid valve disease occurs most frequently secondary to severe left-
LMICs, and more research is needed on outcomes. A center in Thailand sided heart disease. Tricuspid regurgitation in this setting should be
has published reasonable results with a mean 42-month follow-up of addressed at the time of mitral valve surgery if is it severe or if there is
563 patients; however, longer-term follow-up is required in order to significant annular dilatation even in the setting of mild or moderate
make meaningful comparisons between valve repair and valve tricuspid regurgitation. The most common intervention is annuloplasty
replacement.69 reinforced with a band or ring. With primary tricuspid valve disease,
Mitral valve replacement can be performed with either bioprosthetic other techniques such as leaflet augmentation or valve replacement with
valves or mechanical valves. Commercially available bioprosthetic valves a biologic prosthetic should be employed.
are constructed from glutaraldehyde-fixed porcine aortic valve leaflets or In aortic valve disease, the most common intervention is valve
bovine pericardium. These valves have limited durability, especially in replacement with a mechanical or biologic prosthesis. The benefits and
younger patients typical of RHD, but avoid the complications of requisite pitfalls of each type are similar, as in mitral valve replacement. Aortic
lifetime anticoagulation for mechanical prostheses. In Rwanda, where a valve repair is challenging as there is often significant tissue loss and
surgical outcomes registry has been created, early structural valve calcification by the time there is severe valvular dysfunction. There may
degeneration is documented at 11%,70 making mechanical valves be a role for valve repair of mild to moderate stenotic or regurgitant

Figure 4. Operative Interventions for RHD. Mitral valve replacement with a mechanical prosthesis is the most durable operation for RHD; however, it requires
lifelong anticoagulation, which may affect the labor force and women of childbearing age. Mitral repair for RHD has expanded in recent years and has shown good
short- and midterm outcomes. Future innovation will likely focus on biomaterials and transcatheter technologies that can safely improve symptoms in young patients
without the requirement for anticoagulation.
Abbreviations: MVR, mitral valve disease; RHD, rheumatic heart disease.

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M.T. Simpson et al. Structural Heart 7 (2023) 100219

lesions at the time of mitral valve repair.73 In these mildly or moder- medications.78 These medications may be available in LMICs, especially
ately affected valves, enough tissue remains to support a repair. Repair in urban areas; however, lack of health insurance and health literacy may
is an especially good option for children, where the benefit of avoiding result in patients not seeking necessary treatment. As a result, the out-
a prosthesis is multiplied. Techniques are similar to those in mitral comes of patients with CHF in LMIC lag behind those of their developed
valve repair, involving peeling of the leaflets in order to improve height counterparts. Additionally, the LMIC CHF population is significantly
and sharp dissection for commissurotomy or decalcification. As in younger than that of developed countries, resulting in a major social and
mitral valve repair, longitudinal study is required in order to better economic impact.
determine the best candidates for aortic valve repair and its long-term
efficacy. Transcatheter Valve Replacement
There are other options for young patients with rheumatic aortic
valve disease. Recently, the Ross procedure has regained popularity to Over the last decade in industrialized nations, transcatheter aortic
treat aortic valve disease in appropriately selected patients in North valve replacement has revolutionized the delivery of care for valvular heart
America and Europe. There is limited data available on the application of disease. Although these technologies are promising for the treatment of
this operation in rheumatic disease, but there may be a role for its use in RHD, their cost is currently prohibitive for low- and middle-income
young adults.74 However, it does seem that the pulmonary autograft is countries. Additionally, commercially available transcatheter valves in
subject to recurrent valvulitis which may ultimately limit its durability the United States and Europe are constructed of the same materials as
relative to what is seen in industrialized nations. The Ozaki procedure is surgically implanted valve replacements, making them susceptible to
another option available in young patients with aortic valve disease, and structural valve degeneration. The durability of these valves is of real
has been used to treat rheumatic disease.75 Both the Ross and Ozaki concern, especially in the young patients often presenting for surgery for
operations are technically demanding and should be applied only at RHD. Several institutions and companies are evaluating biopolymeric
specialized centers with highly trained surgeons. compounds for the construction of leaflets in transcatheter implantation.
Some show promise in terms of long-term durability and thrombogenic
Management of Atrial Fibrillation potential compared to current technology.79 Other issues for the applica-
tion of transcatheter aortic valve replacement to rheumatic disease include
Atrial fibrillation is common in patients with rheumatic mitral valve variable amounts of calcification in rheumatic valves that make current
disease and may be a source of major morbidity in this population due to devices difficult to deploy accurately. There is improving technology on
its association with stroke. Stroke risk may be mitigated with anti- this front as well, with the development of homing devices.
coagulation; however, anticoagulation use in LMICs is overall lower than Current designs are limited to use in the aortic valve position, which
expected. Systemic issues exist with anticoagulation control; a systematic somewhat limits its potential in RHD. These valves could be used for
review of anticoagulation control and outcomes in African nations shows valve-in-valve procedures in failing mitral bioprostheses; however, this
suboptimal time in the therapeutic window and a high risk of thrombo- requires careful preoperative patient selection, intraoperative imaging
embolic or bleeding complications. There are not clear data demon- capacity, and operator technical expertise.
strating the prevalence of atrial fibrillation and LMICs; however, Although these technologies remain in the preclinical phase, they are
evidence suggests there is under-reporting, especially throughout sub- promising for specific populations where delaying an open operation
Saharan Africa.76 Multiple studies have described the feasibility and ef- would be advantageous or where an open operation is contraindicated. If
ficacy of the Cox Maze procedure at the time of mitral valve intervention. the aforementioned barriers are overcome, it is likely that transcatheter
This procedure is safe; however, may be less effective in patients with operations will significantly change how RHD is treated in LMICs.
rheumatic disease due to the chronicity of arrhythmias and atrial size.
Other complicating factors are the technical difficulty of the cut-and-sew ORCIDs
maze and the availability of contemporary energy sources used for
ablation. Even so, closure or ligation of the left atrial appendage has Amisha Patel https://orcid.org/0000-0002-3289-5705
proven to significantly reduce the stroke risk associated with atrial
fibrillation.77 Contemporary epicardial or endocardial devices available
Funding
in North America and Europe may be difficult or costly to distribute to
areas of need; however, surgical oversewing is a simple and scalable
The authors have no funding to report.
technique that can be done easily at the time of a mitral valve operation.
Arrhythmia associated with valvular disease in LMICs is a field that re-
quires significantly more study and may represent an area in which
Disclosure Statement
cardiologists and cardiac surgeons can collaborate to significantly reduce
morbidity.
The authors report no conflict of interest.

Advanced Presentation
Review Statement
Despite improvements in screening and treatment, many RHD pa-
tients in LMICs will develop congestive heart failure (CHF) as a result of Given his role as an editor, Isaac George, MD, had no involvement in
their advanced valvular disease. While these patients may benefit from the peer review of this article and has no access to information regarding
intervention, advanced disease makes the likelihood of successful its peer review. Full responsibility for the editorial process for this article
percutaneous intervention less likely and increases the operative risk for was delegated to Zoltan Turi, MD.
surgical intervention, which is also more likely to be a valve replacement
as opposed to a repair.
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