Sick sinus syndrome (sss)I49.5

In 1967, Lown was the first to describe rhythm disturbances that occurred after electroconversion of tachycardic atrial arrhythmias. The arrhythmias were related to a disturbed impulse formation and excitation conduction of the sinus node and to a disturbed atrial activity.

Mary Irene Ferrer introduced the term "Sick Sinus Syndrome" in 1968 (Pinger 2019) and summarized the following disorders of the syndrome:

• persistent sinus bradycardia
• Sinus arrest with and without atrial or nodal replacement systole
• Sinus arrest with passable asystole
• chronic atrial fibrillation with a slow ventricular rate not caused by medication
• after electroconversion, the heart is unable to convert from atrial fibrillation to sinus rhythm
• non-drug-induced sinuatrial blockage

In 1973, Kaplan and colleagues proposed the term tachycardia-bradycardia syndrome, the cause of which is predominantly, but not exclusively, a disturbance in the function of the sinus node (Lüderitz 1984).

The Sick Sinus Syndrome (SSS) comprises a group of arrhythmias caused by a disturbance of the sinus node function (Lüderitz 1984). In a quarter of patients with SSS, there is also a disturbance of the AV transition (Kasper 2015).

The SSS is a generic term that summarizes sinuatrial disturbances of the excitation conduction or excitation formation (Stierle 2017).

These include:

• Sinus bradycardia
• Sinus arrest
• Sinuatrial blockages (SA block)
• Bradycardia- tachycardia syndrome (paroxysmal supraventricular tachycardia or atrial flutter or fibrillation)
• chronotropic incompetence of the sinus node (Herold 2020 / Classen 2009)

In addition, a differentiation is made between extrinsic and intrinsic (degenerative) SSS (for more details see Aetiopathogenesis) (Kasper 2015)

An acquired and persistent defect of the AV node cable is extremely rare. The incidence is about 200 per 1 million people. The SSS occurs preferably from the 5th - 6th decade of life. It is found twice as often in women. The reasons are unclear (Brandes 2019; Kasper 2015).

Associated diseases:

Certain diseases accelerate the occurrence of SSS, such as:

• coronary heart disease
• diabetes mellitus
• arterial hypertension
• Cardiomyopathies
• Diseases of the heart valves (Kasper 2015)

A distinction is made between extrinsically and intrinsically caused SSS. The differentiation is important for possible therapeutic measures, since the extrinsic form is often reversible (Kasper 2015).

• Extrinsic causes for sinus node dysfunction can be:
  • hypersensitive carotid sinus
  • vasovagal irritation
  • Medications such as beta blockers, calcium channel blockers, digoxin, lithium, amitriptyline, clonidine, etc.
  • Hypothyroidism
  • Sleep apnea
  • Hypoxemia
  • Hypothermia
  • increased intracranial pressure
  • endotracheal aspiration (vagus maneuver)
• intrinsic causes:
  • coronary heart disease
  • acute myocardial infarction
  • with possible presence of autoantibodies against the sinus node:
    • Cardiomyopathies
    • Pericarditis
    • Myocarditis
  • Lyme borreliosis
  • Senile amyloidosis (see below amyloidoses)
  • Congenital heart disease
  • Currently undergoing radiotherapy
  • Postoperative
  • Previous chest trauma
  • Myotonic dystrophy
  • Idiopathic degeneration of the conduction system (so-called M. Lenégre or M. Lev)
  • mutations congenital disorders of the sodium (SCN5A) and funny (HCN4) ion channels
  • Hereditary forms of sinus node disease (rare) (Kasper 2015 / Herold 2020)

The most common degenerative tissue changes in the SSS are fibrosis in the area of the sinus node and atria. These can be caused by remodelling, e.g. chronic atrial hyperextension, circulatory disorders, etc.

In addition, there are sometimes defects or mutations of the ion channels which lead to a disturbance of the pacemaker function (so-called loss- of- function) (Brandes 2019).

The SSS can be completely asymptomatic and only become manifest by ECG abnormalities. In most cases it is only a reduced perfusion of the end organs that causes symptoms.

Possible symptoms can be:

• Palpitations
• Dyspnea
• angina pectoris
• Signs of heart failure
• Formation of a so-called chronotropic incompetence (inadequate increase of the heart rate under stress) (Herold 2020; Brandes 2019; Kasper 2017)

An SSS should be considered if the following symptoms occur:

• states of exhaustion
• reduced resilience
• Syncopal episodes (Adam Stokes seizures)
• Sinus bradycardia (Kasper 2015)

Long-term ECG: In long-term ECG can exist:

• Sinus bradycardia (< 60 beats / min.; in young or trained patients < 40 / min)
• missing P- waves due to:
  • Sinus arrest
  • Sinuatrial block (SA- Block III)
• SA- Block II
• Tachycardia
• chronotropic incompetence (Kasper 2015)

Exercise ECG: under ergometric stress, a maximum of up to 70 % of the age-related frequency increase can be obtained (chronotropic incompetence) (Herold 2020)

Atropine test: After an i. v. injection of 1 mg atropine, the adequate frequency increase does not occur. The heart rate is still < 80 beats / min. Contraindications for the atropine test are:

• Glaucoma
• benign prostate hyperplasia (Herold 2020)

Determination of the sinus node recovery time (SKEZ): After rapid atrial stimulation with a pacemaker, the time until the sinus rhythm is reached is prolonged and amounts to > 1,500 msec (Herold 2020)

Determination of thyroid function; possible determination of plasma levels of pharmaceuticals such as digitalis (Stierle 2017)

Sinus arrhythmia (Hamm 2014)

Lyme carditis (Gazendam 2020)

In tachy brady syndrome there is a risk of embolic complications (Brandes 2019).

Pacemaker implantation

The implantation of a pacemaker leads to freedom from symptoms for the patient, but does not prolong life expectancy (Pinger 2019).

Implantation is recommended by the AHA, ACC and HRS (Heart Rhythm Society):

• Class I recommendation:
  • symptomatic bradycardia
  • symptomatic sinus pauses
  • symptomatic chronotropic incompetence
  • Atrial fibrillation with bradycardia and pauses of > 5 s
  • indispensable long-term drug administration without acceptable alternatives that trigger an SSS
• Class IIa recommendation:
  • Heart rates of < 40 beats / min without a clear connection to the symptoms described
  • Heart rates of < 40 beats / min under indispensable long-term medication without acceptable alternatives, but without a clear connection to the symptoms described
  • Occurrence of a syncope of unclear genesis when significant abnormalities of sinus function are found or such an abnormality can be provoked
• Class IIb- recommendation:
  • Patients who show only mild symptoms but have chronic heart rates of < 40 / min when awake
• Class III recommendation:
  • asymptomatic patients with heart rates of < 40 / min
  • an initial symptom associated with bradycardia cannot be associated with it
  • Detection of sinus node dysfunction by a dispensable drug therapy (Kasper 2015)

Indication for pacemaker therapy according to ESC 2013:

• Class I: Patients with symptoms clearly attributable to bradycardia
• Class IIb: Patients with symptoms probably due to bradycardia. However, a connection could not be proven with certainty.
• Class III: Asymptomatic patients or patients with reversible cause (Pinger 2019).

An optimal pacemaker system has not yet been found for patients with SSS (Pinger 2019). In the majority of cases a dual-chamber pacemaker is implanted, because patients with SSS have an increased risk for an AV block (Brandes 2019).

1. frequency control:

The frequency can be checked with:

• Beta blockers (e.g. metoprolol, recommended dosage: 100 mg - 200 mg / d or verapamil 3 x 80 mg to 2 x 240 mg / d)
• Digitalis glycosides: Digitalis shortens the sinus node recovery time (Kasper 2015). Recommended dosage e.g. digoxin: slow digitization up to the therapeutic level between 0.8 - 2 ng / ml, followed by daily administration of the maintenance dose of 0.25 mg - 0.375 mg / d, depending on the serum level (Luippold 2012).

2. recurrence prophylaxis:

In case of paroxysmal atrial tachyarrhythmias, recurrence prophylaxis can be carried out e.g. with:

• Amiodarone: Recommended dosage: saturation dose is 5 g - 7 g, maintenance dose is 200 mg - 400 mg / d
• Flecainide: Recommended dosage: 2 x 50 mg - 100 mg / d
• Propafenone: Recommended dosage: 2 - 3 x 150 mg - 300 mg / d (Stierle 2017)

3. anticoagulants:

The risk of chronic atrial fibrillation increases with age in patients with SSS, as do concomitant diseases such as diabetes mellitus, arterial hypertension, left ventricular dilatation, heart valve disease, etc. The resulting increased risk of thromboembolism should be calculated using the CHA2 DS2 - VASc - score (Kasper 2015).

CHA2 DS2 - VASc - Score:

• Chronic heart failure or left ventricular dysfunction: 1 point
• Hypertension: 1 point
• Age ≥ 75 years: 2 points
• Diabetes mellitus: 1 point
• Apoplexy / TIA / Thromboembolism: 2 points
• Pre-existingvasculardisease: 1 point
• Age 65 - 74 years: 1 point
• Sex category (female gender): 1 point (Baenkler 2010))

Degree of recommendation/evidence level ESC 2016 of permanent oral anticoagulation:

• I A:
  • for all male patients with a CHA2 DS2 - VASc - score of 2 or higher
  • for all female patients with a CHA2 DS2 - VASc - score of 3 or higher
• IIa B:
  • for all male patients with a CHA2 DS2 - VASc - score of 1 or higher, taking into account individual characteristics and preferences
  • for all female patients with a CHA2 DS2 - VASc - score of 2 or higher, taking into account individual characteristics and preferences (Kirchof 2016)

In Anglo-Saxon countries, patients are already treated with anticoagulants from 1 point on. For younger women, therapy with ASA can also be considered (Kasper 2015). The risk of a thromboembolism per year at the CHA2 DS2 - VASc - score of:

• 0: 0 %
• 1: 1,3 %
• 2: 2,2 %
• 3: 3,2 %
• 4: 4,0 %
• 5: 6,7 %
• 6: 9,8 %

The risk of intracranial bleeding under therapy with Marcumar (INR between 2.0 - 3.0) is 0.3% / year.

The benefit of antithrombotic treatment is thus significantly higher than the risk of intracranial bleeding. This also applies to therapy with NOAK (Herold 2020).

The risk of severe bleeding can be calculated with the HAS- BLED- Score.

HAS- BLED- Score

1 point each for:

• Arterial hypertension > 160 mm Hg syst.
• (Abnormal):
  • limited liver function (bilirubin > double standard value, AP > 3x standard value
  • or limited kidney function (dialysis, NTX, serum creatinine ≥ 200 µmol / l)
• previous stroke
• anamnestic haemorrhage
• Unstable INR values (less than 60 % are in the therapeutic range)
• (Elderly) older patients (m > 65 years / w > 75 years)
• (Drugs) Medication (such as antiplatelets, non-steroidal anti-inflammatory drugs), drugs, alcohol

There is a low risk of bleeding with a HAS- BLED- score between 0 - 2, a high risk of bleeding from a score of ≥ 3.

The risk of bleeding is with a score of:

• 0 is 1.13 % per 100 patient years
• 3 at 3.74 % per 100 patient years
• 4 at 8.70 % per 100 patient years (Krehan 2017 / Lee 2014)

Choice of anticoagulation:

• I B: Vitamin K antagonists such as warfarin, phenprocoumone (INR 2.0 - 3.0 or higher) in patients with moderately severe mitral valve stenosis or after implantation of mechanical heart valves. These patients should not receive NOAK (Kirchof 2016).
• I A: If there is an indication for a vitamin K antagonist, NOAK should be given in preference to a NOAK such as Apixaban, Dabigatran, Edoxaban or Rivaroxaban, if it is possible.
• IIb A: in patients already pre-treated with a vitamin K antagonist, a switch to NOAK may be made if the TTR is not stable or the patient prefers NOAK and has no contraindications (e.g. valve prosthesis) (Kirchof 2016)

The spontaneous course in patients with SSS is determined by a changing intensity of the severity of the symptoms (Kasper 2015).

Although the symptoms may be severe, overall mortality is not reduced without the presence of other significant concomitant diseases (Kasper 2015).

The prognosis of patients with SSS is similar to that of the normal population. The pacemaker implantation results in freedom from symptoms, but does not prolong life expectancy (Pinger 2019).

A recurrent syncope occurs in about 20% of patients after pacemaker implantation. Patients should be advised of this preoperatively (Pinger 2019).

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