Rheumatic Heart Disease

Rheumatic Heart Disease – Time for a rethink?

Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) are increasingly rare in wealthy societies but remain prevalent in the Third World and marginalized groups. Prophylactic treatments have not changed since the 1950s. There is a need for improved diagnostic and treatment solutions.

One hundred years ago in Western society, Acute Rheumatic Fever(ARF) and Rheumatic Heart Disease (RHD) were common. Many sufferers were condemned to an early death with heart failure. Nowadays these diseases are all but unknown in most resource rich Western societies and interest in research has declined. But the disease is still common in the Third World and in marginalized groups in the West such as Remote Indigenous Communities. Indeed Australia has the highest rates in the world in Remote Northern Territory. We still use prophylaxis developed in the 1950s and treatment remains unchanged

The history of prophylaxis (1)

With the discovery of antibiotics in the 1920s and 1930s, and the linkage of Rheumatic Fever with the infection by Group B streptococcus, attention turned to antibiotic treatment. It was found that Sulphonamides reduced the incidence of recurrent attacks of Acute Rheumatic Fever and progressive valve damage.

When Penicillin was discovered in the 1940s it proved to be even more effective and less prone to side-effects than Sulphonamides. But all these regimes need frequent administration. A poorly soluble depot Penicillin preparation known as Benzathine Penicillin was developed in the 1950s and has remained the mainstay of prophylaxis for RHD ever since. It can be administered by injection every 3-4 weeks. While there has never been a controlled trial of this regime, there is good empirical evidence that it reduces ARF recurrences by two thirds. Group B Streptococcus has remained sensitive to it when many other bacteria have developed resistance. In recent years Benzathine Penicillin has been increasingly difficult to source as drug manufacturers turn to more lucrative drugs. Patients have become more resistant to painful intramuscular injections. In spite of Benzathine Penicillin’s success, there is clearly a need for a better prophylactic solution.

The History of Treatment

Treatment of an episode of Acute Rheumatic Fever remains symptomatic – analgesia for joint pain, antipyretics for fever and Valproate for Chorea. There is no current treatment to reduce the autoimmune mediated damage to heart valves. As far as I am aware there are no treatments under development. Any residual Streptococcal infection is treated with Benzathine Penicillin.

The History of Diagnosis

Acute Rheumatic Fever (ARF) has always been a clinical diagnosis and remains so today. There is no single source of truth – the diagnosis is made on the basis of major and minor criteria as devised by Jones (5). These criteria have been revised and relaxed over time to make them more sensitive. The corollary of this is that they have become less specific, particularly as the disease has become rarer. The “pretest probability” problem comes into play. In a low probability population (RHD is still relatively uncommon, even in Remote settings), a test or intervention with poor specificity will generate many false positives. The symptom/sign that generates most problems is joint involvement. Fever and arthralgia are common in various illnesses. Objective arthritis is less common, polyarthritis even less so. In the early days of the Jones Criteria, 2 major and one minor criterion were required for a diagnosis. This has now been relaxed to one major and two minor criteria. Moreover in the early Jones criteria, the only major criterion involving joints was polyarthritis – ie objective signs of arthritis (redness, warmth, effusion) in several joints. This is now relaxed to allow monoarthritis or even polyarthralgia (subjective pain in several joints) as a major criterion. In practice this means that a patient presenting with fever and arthralgia (common in viral illnesses), but without any other relevant signs can be labelled as ARF. Often the details of a clinical presentation are not recorded. In particular the results of examination of joints may not be available. Other major criteria such as carditis (Echo changes, new murmur, heart failure) and Chorea are more specific and predictive of ongoing RHD. In practice, the oft described eythema marginatum and subcutaneous nodules are rarely seen. Interestingly the finding of PR changes on ECG has never been regarded as a major criterion or evidence of carditis, though it appears to be specific in practice and is easy to perform at first assessment.

Incidence (2,4)

Rates of both ARF and RHD have been increasing in recent years. The reason for this is not clear – I have discussed the possibilities in a previous post

https://tjilpidoc.com/2024/06/13/rheumatic-heart-disease-a-new-epidemic/

In a paper from 2011, after a first ARF diagnosis, 61% developed RHD within 10 years. After RHD diagnosis, 27% developed heart failure within 5 years. So it is important to identify patients with ARF and prevent recurrences with prophylaxis.

There were 172 cases of surgery for RHD in indigenous patients in Australia and NZ in the period 2001- 2012 (3). On average this is less than 20 cases a year.

In 2023 in Queensland, Western Australia, South Australia and the Northern Territory, 97 people underwent surgical events for RHD (one event per person). Most of these (75 people, 77%) were First Nations people. (ref)

So clearly there has been an increase of RHD clients undergoing surgery – is this due to better access or is there a real increase in RHD?

The Northern Territory appears to have a dramatically higher incidence of ARF and RHD than other states with significant indigenous populations such as Queensland and WA. Again the reason for this is not clear – it seems intuitively unlikely that these indigenous populations are less prone to RHD.

Promotion of ARF diagnosis

There has been increased awareness of ARF and RHD in Remote communities in recent years with campaigns to educate health staff and promote the idea that ARF should be considered in patients presenting with fever and joint symptoms. While this is admirable, we know from a 2005 study that many patients entering hospital with a provisional diagnosis of ARF have an alternative at discharge. (6) Because of this promotion, ARF has become the “probability diagnosis” with this scenario in many places. Streptococcal titres have become a defacto criterion when in fact they are a poor positive discriminator of ARF. Diagnostic “precision” appears to have declined with alternatives not considered. Many of these patients do not not have an authoritative assessment by a senior clinician at the time – this is deferred to a later date. This is problematic because relevant clinical symptoms and signs resolve or the patient may not see the clinician at all. Once a provisional label of ARF/RHD is attached to the patient, it can be impossible to remove, even in doubtful cases.

What are the costs of misdiagnosis?

There is a significant imposition on the client with a diagnosis of ARF. They are subjected to monthly injections and periodic reviews for anything up to 10 years. The Health service also bears significant costs. Some of the differential diagnoses of ARF carry significant risk (eg osteomyelitis, septic arthritis, Slipped Capital Femoral Epiphysis). Clearly if these are not treated in a timely fashion there is a risk of long term disability or even death.

Outcomes from different presentations

Many cases of RHD are found when they are already established, presenting as heart failure, murmurs or on screening (eg “Deadly Heart Trek”). Those presenting with Chorea have a high correlation with later development of RHD. While the paper I have previously quoted suggested a high rate of RHD development in all cases of ARF, on my personal review of records those presenting with joint symptoms alone appeared to have a lower rate of development of documented RHD even after some years

Where to from here?

ARF/RHD remains a significant problem in Remote Australia and marginalized groups but treatment and assessment protocols have not changed in recent years. ARF remains a clinical diagnosis. There is a significant rate of misdiagnosis with associated costs and risks. If a single test to prove or disprove ARF could be developed, this would be an advance. There has never been a treatment to reduce the immune mediated harm of ARF. In the age of targeted antibodies, perhaps this issue could be revisited. A better prophylactic drug should also be sought.

In the meantime it should be policy that all new cases of ARF are assessed at the time by a Senior Clinician to avoid “mislabelling” as much as possible.

References

(1) Evolution Evidence and Effect of Secondary Prophylaxis for Rheumatic Fever

Wyber, Rosemary^1,; Carapetis, Jonathan^1,2

Journal of the Practice of Cardiovascular Sciences 1(1):p 9-14, Jan–Apr 2015. | DOI: 10.4103/2395-5414.157554

(2) Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia, 1997 to 2010

Joanna G Lawrence¹, Jonathan R Carapetis, Kalinda Griffiths, Keith Edwards, John R Condon

10.1161/CIRCULATIONAHA.113.001477

(3) A review of valve surgery for rheumatic heart disease in Australia

Elizabeth Anne Russell ^1,2, Lavinia Tran ², Robert A Baker ³, Jayme S Bennetts ^3,4, Alex Brown ^5,6, Christopher Michael Reid ², Robert Tam ⁷, Warren Frederick Walsh ⁸, Graeme Paul Maguire ^1,2,9,✉

BMC Cardiovasc Disord. 2014 Oct 2;14:134. doi: 10.1186/1471-2261-14-134

(4) Recent increases in incidence

AIHW data Acute rheumatic fever and rheumatic heart disease in Australia, Acute rheumatic fever – Australian Institute of Health and Welfare

(5) Rheumatic fever Identification, management and secondary prevention

Australian Family Physician

Volume 41, Issue 1, January-February 2012

https://www.racgp.org.au/afp/2012/january-february/rheumatic-fever

(6) The challenge of acute rheumatic fever diagnosis in a high-incidence population: a prospective study and proposed guidelines for diagnosis in Australia’s Northern Territory

Anna Ralph 1, Susan Jacups, Kay McGough, Malcolm McDonald, Bart J Currie

Heart Lung Circ . 2006 Apr;15(2):113-8.

Rheumatic Heart Disease – a New Epidemic?

The incidence of Rheumatic Heart Disease (RHD) in Remote Australia has apparently increased in recent years. In part this is due to increased screening and possibly improved case finding. But Overdiagnosis due to reduced clinical standards may also explain the increase. The overdiagnosis of ARF can lead to unnecessary burdens on clients and the Health Service and increases the risk of overlooking other serious conditions. This highlights the need for improved diagnostic precision at first presentation.

The incidence of Rheumatic Heart Disease in Remote Australia appears to have increased significantly or even doubled according to some surveys in the last 10 years or so. (1)

What is happening? Are living conditions in Remote Communities getting worse still? Are we finding previously undiagnosed RHD?

We know that Acute Rheumatic Fever(ARF) and Rheumatic Heart Disease(RHD) are diseases of poverty and overcrowding. They are largely unknown in modern urban Australia but still are common in Remote Communities, particularly in NT.

While living conditions in many communities are still “third world” standard, I can find no evidence for further worsening in recent years and my own anecdotal experience over 20 years or so would suggest that things are no worse than they have been in the past. “Closing the Gap” reports show little improvement, but they do not suggest worsening of living conditions and life expectancy.

Are we detecting previously undiagnosed disease?

In my anecdotal experience virtually every person in a community presents to the clinic, often frequently. It seems intuitively unlikely that significant symptomatic heart failure as a result of valve dysfunction would not have been picked up on presentation. Echocardiogram and cardiology review is available for acute symptomatic disease. Heart failure due to acute carditis or deterioration of RHD is uncommon, but can be confused with more common conditions such as pneumonia. Adverse outcomes as a result are likely to occur (https://tjilpidoc.com/2022/03/09/poor-administration-a-health-hazard/)

There has been an understandable promotion of screening by Echocardiogram with programs such as the “Deadly Heart Trek” which have found asymptomatic RHD in some clients. It is generally accepted that prophylactic Penicillin reduces recurrence of ARF and deterioration (though there are no prospective trials to prove this). Thus finding asymptomatic clients and treating them with prophylactic Penicillin would seem intuitively a Good Idea. But like all screening processes it can be difficult to show benefit – whether this screening will result in improved outcomes is yet to be established.

Overdiagnosis

There is one other possible explanation for the apparent increased incidence – that we are over-diagnosing ARF. In recent years there has been promotion of the idea that clinicians have been missing cases of ARF and should be on the lookout for it to reduce the incidence of serious RHD with prophylaxis. Once a diagnosis of ARF is established, even provisionally, that client is subject to a regime of monthly injections and reviews for anything up to 10 years. Many clients are discharged from hospital at their initial presentation without an expert assessment and classification – this is relegated to a later date. But elective Echocardiography and Cardiology review are difficult to access for Remote clients for various reasons. It may be months or even years before these are performed. By this time the relevant clinical signs and data may be lost or otherwise unavailable. As a result even senior clinicians are reluctant to reverse a provisional diagnosis and it can be difficult if not impossible to remove the Rheumatic Fever “label” once it is applied.

ASOT AntiDNAse and streptococcal serology – what is the normal?

Acute Rheumatic Fever increases Antistreptolysin Titre (ASOT). The upper laboratory limit of normal in Australia is 200 IU. But the majority (65%) of asymptomatic subjects had a level >200 IU with some being as high as 800 IU. The level increased with age>10 and season (winter) in an Egyptian study (2). In Australia it is likely to be high in Remote Community subjects because of living conditions and frequent exposure to Group A Streptococcus, but I could find no research on this question for Remote Australia. However, it seems likely that normal levels are much higher than the accepted laboratory range. This makes it a poor positive discriminator for ARF, though it may be helpful in ruling out the disease if it is negative. Similar issues apply in the case of AntiDNAse.(4)

The Clinical Criteria for ARF

Skin infection is common and is the likely source of streptococcal infection in most cases of ARF, at least in the Top End and tropical Australia. (McDonald et al). In spite of this, conventional teaching still sees pharyngitis and tonsillitis as the primary source. Acute Rheumatic Fever remains a clinical diagnosis – there is no independent lab test or other indicator which can reliably discriminate it from other diagnoses. The diagnosis is made on the Jones Criteria, which were first introduced in 1944. They have been modified several times since to increase their sensitivity in low risk populations. This has the effect however of reducing specificity. In reading the references there still seems to be ambiguity, particularly with regard to arthritis/arthralgia. In the most strict version of the criteria, only polyarthritis was allowed as a major criterion – ie several joints involved with objective signs such as effusion and redness. In the more recent versions monoarthritis or even polyarthralgia are allowed as major criteria in high risk areas. Chorea is probably pathognomonic in young people as other causes of acute Chorea are uncommon. “Carditis” can be difficult to define in a Remote setting where echocardiography is not generally available on the spot. A small group of patients present in heart failure due to carditis – these are challenging to diagnose and manage and errors are frequent in this group.

ARF – typical presentations

A common presentation is joint pain or arthritis with or without fever and raised ESR/CRP. Chorea is less common, with acute carditis or other presentations the least common. In my 20 years experience in Remote Health I have not seen the classically described erythema marginatum or subcutaneous nodules. Because of the increased awareness of ARF as a diagnosis, the classical criteria have been relaxed – I have seen a provisional diagnosis of ARF made on a presentation of monoarthritis or even polyarthralgia and raised CRP but without other criteria. ASOT appears to be used as a de facto criterion when it is not a positive discriminator (see above) Enthusiasts argue that any potential harm from overdiagnosis is outweighed by the benefit to a client with true ARF in reducing long term disability with prophylaxis. I would argue that the imposition on clients of an unnecessary diagnosis is not trivial, with monthly painful injections and frequent reviews for up to 10 years or more. There is a workload burden on the Remote Clinic involved and an opportunity cost as a result. The results of misdiagnosis at presentation can be significant – I have personally seen a case of knee pain in a child diagnosed as ARF when in fact it was tibial osteomyelitis and definitive treatment was delayed. On another occasion knee pain was considered to be ARF when in fact the diagnosis was Slipped Capital Femoral Epiphysis. In both these cases the misdiagnosis could have resulted in significant disability. Indeed a study at Royal Darwin Hospital showed that many of the cases admitted with presumed ARF had an alternative diagnosis at discharge. (3)

RHD presentations

The majority of clients with severe RHD requiring surgical intervention or documented valve changes on ECHO either have longstanding RHD with the details of the presentation lost in the mists of time, have presented with heart failure or have been found on Echocardiography screening. No clients who presented with joint symptoms in my case reviews showed evidence of RHD on Echocardiogram. Chorea seems a more reliable criterion with at least some of these subsequently developing RHD changes

Clinical standards

As a practitioner near retirement of course I think things were better in the old days

Our medical clinical training was rigorous with an emphasis on clinical method. This emphasis appears to have been lost in recent years – many clinicians do not take a detailed relevant history of the presentation or refer to previous attendances or past history. Examination is cursory if at all.

We have come to rely on lab testing and imaging for diagnosis when a rigorous clinical method in the hands of an expert clinician remains the most effective diagnostic tool. Many clinicians are nonmedical – they have not undergone the clinical training that doctors go through. There is a heavy reliance on telemedicine, which means that examination is limited. General Practitioners have been largely relegated to administrative tasks and navigating complex chronic disease. Their role in the assessment of acute presentations has been reduced and their opinion is often not respected. They are no longer seen as “expert generalists” at the centre of the clinical process. The assessment of an acute presentation is the classic scenario where masquerades and alternative diagnoses must be considered as well as the “probability diagnosis”. (Murtagh 6) ARF has now become a “probability diagnosis” due to its promotion as a condition which must not be missed. Unsophisticated clinicians often do not consider the alternatives. ARF is a clinical diagnosis. I have noted a tendency in unsophisticated Remote Staff to overreport clinical diagnoses (Otitis media, pharyngitis, bronchiolitis for example). Is this happening with ARF also?

Workforce issues in Remote Australia

The Remote workforce is heavily “casualized” and there is massive staff turnover in most Remote Clinics. Health encounters have become “commoditized” and anonymous – client and clinician often do not know each other. (see previous post) Many Remote Services are struggling to maintain their workforce numbers. These factors further reduce the quality and safety of clinical assessments.

ECHO – how reliable is it?

In file reviews I have noted on some occasions that an echocardiogram was reported as abnormal with Rheumatic changes but subsequent echocardiograms were reported as normal. In one case there was a normal report with abnormal reports before and after. We have always been taught that Rheumatic valve changes do not resolve with time. If this is the case then the quality of echocardiograms must be brought into question. Ultrasonography is a difficult skill, with cardiac ultrasound even more so. Where there is doubt, there is a tendency to overreport changes to avoid missing significant lesions.

Conclusions

The apparent increase in Rheumatic fever and RHD in the last decade can be explained in part by screening and finding asymptomatic patients. But it is likely that the increase in ARF diagnosis is in part due to overdiagnosis, as a result of casualization of the workforce, reduction in clinical standards, promotion of the diagnosis and reduction in the role of expert clinicians such as doctors.

This overdiagnosis has significant consequences for patients and Remote Clinics and it can be difficult to reverse the “label” once it is applied. Any patient admitted with a provisional diagnosis of ARF should undergo careful assessment by a senior clinician before discharge and classification as ARF. While it is important not to miss cases of ARF, we should be aiming to improve our diagnostic precision so that we do not impose an unnecessary burden of treatment on clients and the health service, and do not miss other potentially serious conditions.

An answer should be sought to the question – Do RHD changes resolve with time? Echocardiogram is a difficult skill – there is a need for review of some results and rigorous standards.

References

(1) AIHW Acute Rheumatic Fever and Rheumatic Heart Disease in Australia 2022

https://www.aihw.gov.au/reports/indigenous-australians/arf-rhd-2022/contents/arf

(2) Antistreptolysin O titer in health and disease: levels and significance

Alyaa Amal Kotby, Nevin Mamdouh Habeeb, and Sahar Ezz El Elarab

Pediatr Rep. 2012 Jan 2; 4(1): e8.

(3) The challenge of acute rheumatic fever diagnosis in a high-incidence population: a prospective study and proposed guidelines for diagnosis in Australia’s Northern Territory

Anna Ralph 1, Susan Jacups, Kay McGough, Malcolm McDonald, Bart J Currie

Heart Lung Circ . 2006 Apr;15(2):113-8.

(4) Detection of upper limit of normal values of anti-DNase B antibody in children’s age groups who were admitted to hospital with noninfectious reasons

Servet Delice,1 Riza Adaleti,2 Simin Cevan,3 Pinar Alagoz,4 Aynur Bedel,5 Cagatay Nuhoglu,5 and Sebahat Aksaray2

North Clin Istanb. 2015; 2(2): 136–141.

(5) Low rates of streptococcal pharyngitis and high rates of pyoderma in Australian aboriginal communities where acute rheumatic fever is hyperendemic

Malcolm I McDonald 1, Rebecca J Towers, Ross M Andrews, Norma Benger, Bart J Currie, Jonathan R Carapetis

Clin Infect Dis . 2006 Sep 15;43(6):683-9.

(6) General Practice 8^th edition

John Murtagh

Poor Administration – a Health Hazard?

A recent 4 Corners program has highlighted the risks faced by Remote clients with Rheumatic Heart Disease. (RHD) (ref)

RHD is a disease now all but unknown in “polite society” ie the rest of Australia. But it remains common in Remote communities. The risk factors are well known – poor housing with the resultant overcrowding and poor hygiene. As a result of this Skin Sores are common. These are colonized or caused by Group A Streptococcus which drives the high incidence of Rheumatic Fever. The Housing issue has been described in many Government reports over many years but appears to be as immutable as ever.

The 4 Corners Program describes the journey or four patients with RHD in a Queensland Clinic – there appears to have been a delay in managing the deterioration of the condition.

Similar cases are occur regularly in all Remote environments.

As ever it is tempting to blame the individual clinicians for the poor outcomes. But are there systemic issues in our health system that are contributing to the problem?

The Presentation

Deterioration in RHD is an unusual but not rare presentation. It may mimic other conditions such as Pneumonia with cough, shortness of breath and fever. The deterioration may be due to a further attack of Rheumatic Fever and Carditis (inflammation of the heart) causing heart valve damage, or perhaps bacterial infection of an implanted valve prosthesis. An unsophisticated Clinician may mistake this for a more common condition such as Chest Infection, particularly if the relevant information about the RHD is not prominent in the record.

The Clinician

Remote places are difficult to staff – most initial encounters occur between a client and Remote Area Nurse (RAN) or Aboriginal Health Practitioner (AHP). Doctors are not resident in most Remote places but visit on an intermittent basis for planned consultations. Remote staff perform sterling work in the face of difficult conditions. They provide a very competent emergency service. However nonmedical staff do not have the sophisticated clinical training that doctors undergo. They are are less able to manage an unusual or nontypical presentation.

The “Anonymous Consultation”

Staff turnover is accepted as normal in Remote practice. Typical figures in Remote Clinics are in the order of 150% turnover each year. It is estimated that reducing this turnover by half would save $32M per year in NT (ref). In spite of these costs, policy makers seem content to accept the current situation – staff turnover is not a “KPI” or even actively measured. There do not appear to be active programs to reduce it.

But what are the risks of rapid staff turnover to clinical standards and safety? Was this a relevant factor in these cases? In my own personal experience a large proportion of consults in Remote practice are “anonymous” – ie the client and clinician have not met before. My own personal surveys in various Remote locations have found consistently that for every 10 consultations, a client sees 6-7 different clinicians.

If the clinician assessing the case had met the client before and knew them previously, would they have seen a deterioration in their condition? Would they have ensured that they had received notice of appointments and that the client attended? Would the client have been able to communicate better? Would the clinician have taken more notice of their story?

In my view a relationship with the client is important in managing long term conditions, and the answer to these questions is yes. It also means that there is less reliance on electronic systems of recall and administration.

The Record and Data Visibility

Health is ever more complex, with new treatments and subspecialties appearing all the time. There is a push to standardize and systematize clinical interaction with Careplans and treatment protocols. In theory this will “commoditize” clinical encounters, allowing them to be conducted by any clinician with the relevant training. A personal relationship between client and clinician is at least in theory less important. Care is compartmentalized with different clinicians dealing with different issues. The role of the General Practitioner “Expert Generalist” has been devalued.

Of course, all this creates complexity in the medical record with Careplans, referrals, appointments, treatment items and letters. The Medical Record is now Electronic – if this system is not well designed, relevant information can lost in the “noise” of all this process. In many systems interface design has not been high priority – there are redundant dialogs and headings, critical data may be hidden in poorly labelled secondary dialogs. The noise is further exacerbated by administrative information such as travel and appointment letters cluttering the record.

There may be further administrative problems, with relevant letters never reaching the record or appointments never being notified.

These systemic administrative failures are safety issues which should be part of Quality and Safety reviews, but are not addressed as such. Reviews focus on the performance of individual clinics and clinicians but rarely address systemic issues.

Conclusion

In general Remote Health Services provide a high quality response in Primary Care and Emergency Care under difficult conditions.

However, the combination of an unusual but serious presentation, an “anonymous” clinical encounter and poor administrative and record systems can be deadly.

Administrative and management performance should be part of Safety and Quality Review. In particular the massive staff turnover which is routine in Remote Health should be measured and addressed as a priority. The content and interface design of Electronic Medical Record Systems should also be regarded as a safety issue, with more effort being put into this part of their design.

References

4 Corners

https://www.abc.net.au/news/2022-03-08/doomadgee-hospital-health-service-rhd-women-deaths/100887674