This study is divided into two parts:

• The first part evaluates the acute effect of non-pharmacological heart rate change on central hemodynamic parameters noninvasively in sick sinus syndrome patients with a permanent cardiac pacemaker
• The second part evaluates the acute effects of atenolol, nebivolol and ivabradine on central hemodynamic parameters noninvasively in sick sinus syndrome patients with a permanent cardiac pacemaker at different pacing rate levels

Patients with sick sinus syndrome and a double-chamber cardiac pacemaker are studied.

• To investigate the role of non-pharmacological heart rate change on central hemodynamics in the first part of the study, the investigators acutely change pacing rate from atrial paced-atrial sensed (AAI)-mode 60 to 40 to 90 bpm and obtain hemodynamic parameters noninvasively after a short stabilisation period after each pacemaker rate change.
• Subsequently, to investigate the acute effects of beta-blockers or ivabradine on central hemodynamics in the second part of the study, the investigators obtain central hemodynamic parameters noninvasively after acute administration of atenolol, nebivolol or ivabradine at the same pacing rate levels used in the first part of the study (AAI-mode 60, 40 and 90 bpm).

Inclusion Criteria:

• age 18-75 years;
• dual-chamber pacemaker implanted due to sick sinus syndrome at least six months before; sinus rhythm

Exclusion Criteria:

• average seated office brachial systolic BP ≥160 mmHg and/or diastolic BP ≥ 100 mmHg; atrial pacing <40%;
• ventricular pacing >25%;
• unpaced QRS >120 ms and/or QTc >500 ms on 12-lead ECG;
• atrioventricular blockage at AAI-mode 90 bpm; resting HR >60 bpm at AAI-mode 40 bpm; irregular heart rate;
• automatic mode switching >10%;
• implantable cardioverter defibrillator or cardiac resynchronisation therapy pacemaker; treatment with digoxin, class Ic or III antiarrhythmic drugs;
• history of acute coronary syndrome;
• stable angina pectoris;
• heart failure with reduced left ventricular ejection fraction;
• history of cerebrovascular event;
• diabetes mellitus;
• chronic kidney disease with eGFR <30 ml/min/m2;
• peripheral artery disease;
• clinically relevant heart valve disease;
• active cancer;
• acute or chronic inflammatory disease;
• severe chronic respiratory or liver disease;
• pregnancy or breastfeeding
• contraindication or intolerance to atenolol, nebivolol, ivabradine or adjuvants

all data shared after completion of study as supplement to journal article