Introduction

Kearns-Sayre syndrome (KSS) is a rare, progressive neuromuscular disorder that affects multiple organs and systems throughout the body, including the heart and eyes.¹ Defects in the mitochondrial DNA cause KSS, and it typically manifests before the age of 20. The risk of developing cardiac involvement and sudden cardiac death (SCD) is very high in patients with KSS. Cardiac manifestations occur in up to 57% of KSS patients, and sudden cardiac death has been reported in up to 20% of KSS patients.³ 

Progressive electrical conduction defects involving a breakdown in the heart's electrical signalling pathways, potentially causing bradycardia (slow heart rate), can cause heart block or even SCD. Early prophylactic pacing (implantation of a pacemaker) is vital due to the progressive nature of the disease, and implementing a pacemaker improves survival and symptom monitoring for KSS patients. This article explains why cardiac management is vital, how pacemakers work in KSS, and why there is a need for ongoing monitoring. 

Understanding the cardiac risks in KSS

The heart has an electrical wiring system called the conduction system, which keeps the heart beating. It is made up of the sinoatrial node, atrioventricular node, and the bundle of his and Purkinje fibres. All of this structure allows electrical signals to pass through, pushing blood out of the heart to your lungs and the rest of your body.⁴  

The most typical cardiac complication typically begins with the left anterior fascicular block, sometimes accompanied by the right bundle branch block, both of which can serve as warning signs and can progress rapidly to complete atrioventricular (AV) block. AV block is categorised into three degrees with increasing severity and danger.

The degrees include:

• 1st degree AV block: Here, the electrical signal is slowed, but it still reaches the ventricles. It has often been shown by a prolonged PR interval on an ECG and is not serious, nor does it require treatment
• 2nd degree AV block: the signal is sometimes blocked, meaning some atrial beats do not make it to the ventricles. This can be asymptomatic or cause dizziness and fainting
• 3rd degree AV block: the signal is completely blocked, making the atria and ventricles beat independently. This is the most severe form, and it requires the use of a pacemaker⁶ 

Sick sinus syndrome (SSS) is another cardiac complication in KSS patients where the heart's natural pacemaker, the SA (sinoatrial) node, malfunctions, which leads to irregular or slow heartbeat. Ventricular arrhythmias are less common than block, but they can potentially be more serious. Cardiomyopathy can further exacerbate cardiac complications as it is characterised by a weak heart muscle. 

These cardiac complications are directly related to the mtDNA deletions that cause KSS, resulting in the loss of genes important for protein formation and oxidative phosphorylation. This leads to a decrease in cardiomyocytes, and therefore, dysregulation of the heart's functions, such as those of the SA node. As seen with atrioventricular block, symptoms might be absent or subtle until a severe event occurs, which is why proactive monitoring is key. 

Diagnosing cardiac issues: The first line of defence

Patients with KSS should have an essential annual checkup of their heart, even if they have no symptoms, as they can detect potentially lethal issues. 

Some of the key diagnostic tools include:

• Electrocardiogram (ECG/EKG): A test that records the electrical activity of the heart, including the rate and rhythm. It helps diagnose heart attacks and arrhythmias (irregular heartbeats)⁷
• Holter monitor: This is a small, wearable device that records the heart's rhythms, usually for 1-2 days. It is similar to an ECG and is used when the traditional ECG does not provide enough details about the heart's condition⁸ 
• Event monitor/loop recorder: A device that monitors and records the heart's activity, and also detects and diagnoses arrhythmias for some time (days or weeks). An external event monitor is worn temporarily, and an implantable loop recorder is surgically placed under the skin⁹ 
• Echocardiogram: A scan that is used to look at the heart structure and blood vessels. It uses a small probe that sends out high-frequency sound waves, which bounce off the heart muscle and are converted into a moving image¹⁰

These diagnostic tools can detect characteristics such as a prolonged PR interval, also known as first-degree AV block, which indicates a delay in the electrical signal on an ECG. Although it is benign on its own, this can be a marker for underlying heart conditions. Analysing the shape of the QRS complex on the ECG waves can identify any right or left bundle branch block, which also signifies a delay or blockage in electric impulses to the ventricles, revealing abnormalities. 

Seeing a specialised cardiologist is essential for KSS, as it allows for a better understanding and recognition of the cardiac complications associated with this mitochondrial disease. It will enable tailored treatment plans that require a deep understanding of the interplay between cardiac and mitochondrial function, as well as early interventions, such as pacemaker placement, to prevent life-threatening complications. 

Pacemakers: A lifesaving intervention

A pacemaker is often needed when the heart's natural electrical system, specifically the SA node, malfunctions, leading to a slow heart rate or even cardiac arrest. The pacemaker acts as a substitute, sending electrical impulses to maintain a regular and appropriate heart rhythm. It is a small, battery-powered device that is placed under the skin near the collarbone. 

There are different types of pacemakers:

• Single-chamber pacemaker: This usually sends electrical signals to the lower right chamber of the heart
• Dual chamber pacemaker: Sends signals to the upper and lower right heart chambers 
• Biventricular pacemaker: Also known as a cardiac resynchronisation pacemaker, this device is used for individuals with heart failure and a slow heartbeat. This stimulates both lower chambers of the heart and improves heart muscle strength

Pacemaker implantation is often recommended prophylactically, especially for significant conduction system diseases, like second-degree AV block or advanced bundle branch block, even before symptoms of complete heart block develop. This preventative approach is a crucial strategy for managing KSS syndrome. Early pacemaker placement aims to prevent potentially dangerous complications like symptomatic bradycardia, decreased cardiac output, and sudden cardiac arrest. 

The pacemaker implantation procedure is relatively straightforward, often performed under local anaesthesia, though general anaesthesia may be used in some cases. A small incision is made, typically near the collarbone, and leads are guided through a vein into the heart. The pacemaker generator is then placed under the skin in the same area. 

Life with a pacemaker: beyond implantation

After the procedure, you are typically sent home the same day or the next, and you need to keep the incision dry. Avoid any strenuous arm activities initially, and return to normal activities after 4 to 6 weeks. Regular checkups are also essential to ensure the pacemaker is functioning correctly, as the pacemaker stores information about the heart's rhythm. The follow-up appointments can consist of the doctor retrieving the information to check how well the heart and pacemaker are responding in conjunction with each other. 

Pacemaker batteries typically last between 5 and 15 years. When the battery nears the end of its life, the pacemaker unit, including the battery, needs to be replaced. However, this procedure is usually more straightforward and quicker than the initial implantation. Anything that generates a strong electromagnetic field, such as an induction hob, can interfere with a pacemaker; therefore, it is essential to maintain a safe distance.

Ongoing monitoring: vigilance for life

While a pacemaker is a vital lifeline for managing serious heart rhythm problems in KSS, it does not mean cardiac monitoring can stop. This is crucial because KSS is a progressive disorder, and new electrical conduction issues or dangerous arrhythmias can develop over time, even beyond the specific problem your current pacemaker addresses. Additionally, the risk of cardiomyopathy (weakening of the heart muscle) often increases as the disease progresses, requiring separate vigilance.

The pacemaker itself also needs ongoing surveillance to ensure its battery is strong, its leads are intact, and it is pacing your heart appropriately. Therefore, lifelong, proactive monitoring remains essential. This includes regular cardiology visits, annual ECGs and Holter monitoring to detect new or worsening electrical abnormalities, regular echocardiograms to assess heart muscle function, and routine pacemaker interrogations to verify device function.

Most importantly, you must maintain constant symptom awareness. Any new or worsening symptoms, such as fainting, dizziness, excessive fatigue, palpitations, or shortness of breath, require immediate medical attention. Never dismiss these symptoms as "just part of KSS" or assume the pacemaker will automatically handle it. Vigilant monitoring is crucial for detecting and mitigating emerging threats promptly.

Conclusion

Managing the cardiac risks of Kearns-Sayre syndrome hinges on two critical pillars: the lifesaving intervention of pacemakers for serious conduction blocks and the lifelong commitment to vigilant monitoring. These proactive approaches are not merely advisable; they are essential, as they significantly improve both life expectancy and the quality of life for individuals with KSS. 

Strict adherence to your scheduled monitoring appointments, including cardiology visits, ECGs, holters, echos, and pacemaker checks, combined with open and immediate communication with your healthcare team about any new symptoms, forms the bedrock of adequate care. By embracing this vigilance and partnership, individuals with KSS can confidently manage their cardiac health and live fuller and more empowered lives.