IntegRAted chronic care program at specialized AF clinic versus usual CarE in patients with Atrial Fibrillation, a Multicenter Randomized Controlled Clinical Trial

The primary endpoint is a composite, defined as unplanned admission to the

hospital for any cardiovascular reason and cardiovascular death.

The endpoint events leading to unplanned hospitalisation or death are

therefore:



1. Left or right ventricular heart failure which is independent of LVEF

(preferably confirmed by biomarker assessment using NT-pro-BNP) and requiring

intravenous diuretics or an unplanned hospitalisation without admission when

any adjustment of heart failure therapy suffices;



2. Ischemic thromboembolic complications including stroke (the sudden onset of

a focal neurologic deficit in a location consistent with the territory of a

major cerebral artery caused by an arterial thrombus in this artery,

categorized as ischemic stroke and TIA (transient stroke, whereby clinical

symptoms disappear within 24 hours))confirmed by a neurologist on the basis of

computerised tomography or MRI; peripheral emboli, pulmonary emboli or systemic

emboli (an acute vascular occlusion of an extremity or organ) documented by

means of imaging, surgery or autopsy;



3. Acute coronary syndrome (STEMI/ NSTEMI/ unstable angina pectoris, with at

least two of the following characteristics: (1) typical chest pain for at least

20 minutes; (2) ischemic electrocardiographic changes, and (3) cardiac enzyme

elevation more than twice the upper limit of normal or instable angina

pectoris, respectively documented on ECG as well as/ or only in blood levels of

key chemical markers);



4. Major bleeding(an acute bleeding with the hemoglobin value decreased by > 20

g/ L (>2g/ dL; 1,2 mmol/l), or requiring blood transfusion of at least two

units of blood, or a symptomatic bleeding in a critical organ or area

(intra-cranial (intracerebral hemorrhage, subdural hemorrhage or subarachnoid

hemorrhage), retroperitoneal, spinal, ocular, pericardial, or a traumatic

articular) or fatal bleeding;



5. Arrhythmic or potential arrhythmic events (atrial fibrillation, -flutter,

other supraventricular rhythm or sustained ventricular tachycardia confirmed by

ECG, > 30 sec), syncope (a sudden temporary loss of consciousness associated

with a loss of postural tone with spontaneous recovery not requiring electrical

or chemical cardioversion) or cardiac arrest (circulatory arrest necessitating

resuscitation and hospitalisation) or an unplanned hospitalisation without

admission with any adjustment required to rate or rhythm control therapy, and



6. Life-threatening adverse effects of rate or rhythm controlling drugs (any

pro-arrhythmia of Vaughan Williams classes I and III anti-arrhythmic drugs,

digitalis intoxication, drug-induced heart failure or conduction disturbances

required hospitalisation);





Cardiovascular deaths were classified according to a modified Hinkle and Thaler

classification (Hinkle et al., 1982).



Cardiovascular mortality

Death from a diagnosed cardiovascular cause, classified as cardiac arrhythmic,

cardiac non-arrhythmic, or a vascular non-cardiac cause.



Cardiac, arrhythmic

Death from rapid ventricular tachycardia or fibrillation and had this rhythm

not occurred the patient would have probably survived for at least 4 months.

Loss of cardiac output and pulse is sudden and precedes collapse of the

circulation (defined as a state of very low cardiac output, poor peripheral

perfusion, systolic blood pressure of less than 80 mm Hg, or dependence on

intravenous inotropic support) or severe pulmonary oedema, characterised by

severe respiratory distress of sudden onset without evidence of non-cardiac

cause. The patient is not already in shock or pulmonary oedema at the time of

onset of the arrhythmia.



Cardiac, non-arrhythmic

The patient develops collapse of the circulation or is in shock or severe

pulmonary oedema before loss of cardiac output and fatal arrhythmia. Special

categories included monitored patients who had profound bradycardia or

asystole, or a rhythm generally compatible with normal cardiac output, and,

therefore, probably electromechanical dissociation, immediately before abrupt

circulatory collapse.



Vascular, non-cardiac

For example, aortic dissection, ruptured aneurysm, other haemorrhage, cerebral

vascular accident, pulmonary embolus.





Definitions for the components of the primary endpoint

Cardiovascular mortality

Death from a diagnosed cardiovascular cause, classified as cardiac arrhythmic,

cardiac non-arrhythmic, or a vascular non-cardiac cause.



Heart failure

Heart failure independent of LVEF (preferably confirmed by biomarker assessment

using NT-pro-BNP) necessitating hospitalisation and requiring intravenous

diuretics, or other adjustments of heart failure therapy during hospitalisation.



Stroke

A disabling hemorrhagic, ischemic, or undetermined stroke confirmed by a

neurologist on the basis of computerised tomography or magnetic resonance

imaging and necessitating hospitalisation.



Systemic emboli

An acute arterial occlusion of an extremity or organ. Have to be confirmed by a

physician, typically with some type of imaging and necessitating

hospitalization.



Acute coronary syndrome

STEMI/ NSTEMI Myocardial infarction with at least 2 of the following: (1)

typical chest pain for at least 20 minutes; (2) electrocardiogram showing

changes of acute myocardial infarction; and (3) cardiac enzyme elevation more

than twice the upper limit of normal or instable angina pectoris, respectively

documented on ECG as well as/or only in blood levels of key chemical markers,

necessitating hospitalisation.



Bleeding

A bleeding with the hemoglobin value decreased by > 20 g/ L (>2g/ dL) or

requiring blood transfusion or symptomatic bleeding in a critical organ or area

(intra-cranial, retroperitoneal, spinal, ocular, pericardial, or a traumatic

articular) or fatal.



Arrhythmic events

Includes episodes of atrial fibrillation and syncope, necessitating

hospitalisation, or adjustments in rate- or rhythm control therapy during

hospitalisation.



Syncope

A sudden temporary loss of consciousness associated with a loss of postural

tone with spontaneous recovery not requiring electrical or chemical

cardioversion.



Sustained ventricular tachycardia

Lasting more than 30 seconds and must be documented on electrocardiogram (ECG)

and requires hospitalization.



Cardiac arrest

Circulatory arrest necessitating resuscitation and hospitalization.



Life-threatening adverse effects of rate or rhythm controlling drugs

Pro-arrhythmia of classes I and III anti-arrhythmic drugs, digitalis

intoxication, drug-induced heart failure or conduction disturbances and

ventricular arrhythmias necessitating hospitalisation.

The secondary endpoints are:

1. The cost benefit of the intervention by means of a cost effectiveness

analysis;

2. The extent to which the comprehensive cardiovascular treatment is in

accordance to the latest ESC guidelines for AF, HF guidelines

of acute and chronic heart failure and CVD Prevention guidelines;

3. Patient quality of life and satisfaction;

4. Patient anxiety and/ or depression;

5. Patients* knowledge of AF and

6. Patients* compliance in medication.