Introduction 

Endocarditis and rheumatic fever - both causing inflammation of the heart - are two different diseases that intertwine closely. Acute rheumatic fever can cause endocarditis, and it can also progress into a chronic condition called rheumatic heart disease, a significant risk factor for endocarditis. This article provides an overview of endocarditis, acute rheumatic fever and rheumatic heart disease highlighting their connections and impacts. 

What is infective endocarditis? 

Infective endocarditis occurs when bacteria, fungi, or other microorganisms enter the bloodstream and reach and attack the tissues in the heart, leading to the inflammation of the endocardium the inner lining of the heart chambers and valves. Implanted devices like pacemakers, artificial valves, or defibrillators are also good soil for endocarditis.¹ 

The most common ways for bacteria to enter the bloodstream are through:¹ 

• Minor mucosal injuries, for example, during brushing teeth
• Medical procedures in areas where bacteria are common on the surface, like dental procedures, invasive procedures in the urinary, gastrointestinal or respiratory tract 
• Surgeries of infected areas 

People with certain pre-existing heart conditions or with mechanical valves are more prone to infective endocarditis. Thus, when they undergo invasive procedures, they often receive a single dose of antibiotics before the intervention. They (as everyone else) should also maintain good oral hygiene.¹ 

Untreated, endocarditis damages the heart valves permanently. Although effective treatments, such as intravenous antibiotics and valve replacement surgery are available, it still has a 25 % mortality rate.² 

The symptoms of endocarditis^3,4,5 

Symptoms are variable. Some are less specific, like 

• Prolonged fevers 
• Night sweats 
• Fatigue, weakness
• Joint pain 
• Muscle aches and pains 
• Weight and appetite loss 

More specific symptoms are: 

• New cardiac auscultatory findings 
• Petechiae, bleedings 
• Roth’s spots (a finding through fundoscopy: red spots with white or pale centres on the retina) 
• Janeway lesions (small, non-painful red-coloured spots on the palms or the soles of the foot) 
• Osler nodes (painful purple-pink nodules on the hands and feet) 
• Enlarged spleen 
• Embolic phenomena 

If you notice any of these symptoms, you should seek medical help immediately. 

How common is infective endocarditis? 

The number of new cases per year remains consistently high; however, the underlying causes have changed over time and according to geographical location.⁴ 

With the rise of modern medicine and the widespread use of intravenous lines and implanted cardiac devices, 25-30 % of all causes nowadays are healthcare-associated endocarditis. 

Global differences 

In developed countries, infective endocarditis is more common in men, particularly in those older than 67 years. Yet, in socioeconomic groups with a higher risk of intravenous drug use, it also affects younger people.⁵ 

The most common risk factors for infective endocarditis in developed countries are:⁵ 

• Intravenous drug use 
• Degenerative valve disease 
• Prosthetic valves 
• Indwelling catheters 
• Implanted cardiac devices 
• Diabetes 
• Immunosuppression 
• Chronic heart disease 

In the developing world, on the other hand, the most significant risk factor remains rheumatic heart disease, a complication of acute rheumatic fever.⁵ 

What is acute rheumatic fever? 

Acute rheumatic fever (and rheumatic heart disease) is a complication of an untreated or inadequately treated throat infection caused by a bacteria from the group A streptococci (GAS).² The immune system mistakes its own tissues for GAS bacteria and attacks different organs causing various symptoms.^6,7 Symptoms of acute rheumatic fever occur 2-3 weeks after the throat infection,⁸ mainly in children and adolescents between the ages of 5-15 years.⁹ 

We can observe a geographical inequality in the occurrence of the disease. In Europe and North America, we hardly see any cases. At the same time, acute rheumatic fever remains a serious health concern in most parts of the world. It is one of the most common causes of cardiovascular diseases and premature death, especially in developing countries.⁶ 

The role of GAS bacteria⁷ 

The GAS bacteria, especially in low-and middle-income countries or populations with limited resources are among the top ten causes of death. 

GAS bacteria are responsible for superficial infections such as 

• Scarlet fever 
• Impetigo 
• Pharyngitis 

They also can cause invasive infections like 

• Cellulitis 
• Necrotizing fasciitis 
• Skeletal infections 
• Sepsis 
• Toxic shock syndrome 

GAS infection and its consequences 

The GAS infection triggers a defence reaction of the immune system, which can lead to autoimmune responses in susceptible people. The immune system releases antibodies to fight the invading bacteria. These antibodies may identify heart, nerve, and joint tissues as bacteria and attack them.^7,8 

They mistakenly attack their own tissues and can cause several delayed complications after a GAS infection like:⁷ 

• acute rheumatic fever/rheumatic heart disease 
• post-streptococcal glomerulonephritis 
• PANDAS syndrome: paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections 

What happens in acute rheumatic fever? 

In acute rheumatic fever, the immune system may attack various organs, causing different symptoms. The organs involved are:⁷ 

• Heart 
• Joints 
• Brain 
• Skin 
• Subcutaneous tissue

Clinical symptoms represent the affected organs:^6,7 

• Inflammation of the heart (in 50%–70% of all cases) 
• Inflammation and pain in the joints (in 35%–66 of all cases) 
• Sydenham’s chorea, a neurologic disorder (in 10%–30% of all cases, more common in girls)
• Erythema marginatum (in <6% of all cases, a rash, a highly specific symptom of acute rheumatic fever) 
• Subcutaneous nodules (in 0%–10% of all cases) 

In most tissues, the damage resolves typically in a couple of weeks to months. However, the damage to the heart is irreversible, and with repeating episodes of acute rheumatic fever, it worsens.

Heart inflammation occurs in 60% of the patients during an episode of acute rheumatic fever. These patients, if left undiagnosed and untreated, will likely suffer from a chronic condition called rheumatic heart disease residual valvular damage in the heart.^8,9 

Diagnosing acute rheumatic fever 

The diagnosis of acute rheumatic fever is based on clinical and laboratory criteria, first described in 1944 by Dr T. Duckett Jones. Therefore, we call them the Jones criteria.⁹ They label symptoms and values as major or minor criteria.⁶ 

In patients with evidence of previous infection, two criteria or one major plus two minor criteria are essential to make the diagnosis.⁶ 

The major Jones criteria are:⁶ 

• Carditis: Inflammation of the heart
• Polyarthritis: Inflammation of multiple large joints(at least five joints) 
• Chorea 
• Erythema marginatum 
• Subcutaneous nodules
• Joint pain in several joints (only valid in moderate- and high-risk populations) 
• Inflammation of only one joint (only valid in moderate- and high-risk populations) 

The minor Jones criteria are:⁶ 

• Joint pain in several joints 
• Fever (≥38.5°C) 
• ESR (erythrocyte sedimentation rate) ≥60 mm in the first hour and/or CRP (C-reactive Protein) ≥3.0 mg/dL 
• Changes in the electrocardiogram: prolonged PR interval after accounting for age variability (unless carditis is a major criterion) 

The following may be present in moderate-high risk population

• Joint pain in only one joint
• Fever (≥38°C) 
• ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL

Sometimes, chorea may be the only symptom patients experience through an episode of acute rheumatic fever. In these exceptional cases, the presence of chorea is enough to make the diagnosis.⁶ 

The management of acute rheumatic fever⁷ 

The timely and precise diagnosis and treatment of acute rheumatic fever is crucial for preventing rheumatic heart disease, a late complication of acute rheumatic fever.

Adequate management requires 

• The eradication of the cause: antibiotics against the GAS bacteria (usually penicillin) 
• Symptomatic treatment of fever, pain, etc.

From acute rheumatic fever to rheumatic heart disease 

If acute rheumatic fever remains undiagnosed, episodes can repeat and cause progressive damage to the heart leading to a condition called rheumatic heart disease.^7,8 

Rheumatic heart disease is a chronic condition, usually silent, presenting no symptoms until its manifestation in adulthood with one or more complications, like:¹⁰ 

• Heart failure 
• Pulmonary hypertension 
• Atrial fibrillation 
• Decreased left ventricular ejection fraction 
• Increased left ventricular end-diastolic diameter 

Rheumatic heart disease causes cardiovascular diseases and early death in the younger population worldwide.⁹ It can necessitate valve replacement surgery and increases the risk for:^7,8 

• Infective endocarditis 
• Stroke 
• Heart failure 
• Premature death 

The peak of its occurrence is decades after the first episode of acute rheumatic fever, usually between the age of 25-45 years.⁹ 

According to WHO statistics, “rheumatic heart disease is the most commonly acquired heart disease in people under age 25.” 

The prevention of acute rheumatic fever and rheumatic heart disease 

The decline of both diseases in high-income countries is mainly attributed to better hygiene, easier access to antibiotics and primary care, better housing and other socioeconomic factors.⁶ 

Access to primary healthcare seems to impact numbers the most,⁹ underlining the role of identifying and treating group A streptococcal throat infections early and adequately.⁸ 

To prevent acute rheumatic fever, we should administer antibiotics no more than nine days after throat infection symptoms begin.⁸ If we leave the throat infection by GAS bacteria untreated and acute rheumatic fever occurs, we can still prevent recurring episodes and rheumatic heart disease with long-term benzathine penicillin G (BPG) injections. Patients should receive penicillin injections regularly (every 3-4 weeks) for ten years after the infection or until the age of 21.⁸ 

Summary 

Infective endocarditis is a life-threatening infection of the heart's inner lining that affects the valves. It can also appear in nonvalvular areas or on implanted devices.

In different parts of the world, different processes lead to infective endocarditis. In developing countries, the main cause is acute rheumatic fever, a sequel of untreated or inadequately treated throat infection. Rheumatic heart disease, a late complication of acute rheumatic fever, also contributes significantly to the high numbers of infective endocarditis. 

These inflammatory processes are responsible for cardiovascular diseases and premature deaths among young people in low- and middle-income countries. Thus, access to primary health care, early diagnosis, and treatment of throat infections or acute rheumatic fever is crucial in preventing late complications and death in the affected population.