Antiarrhythmische Therapie - Universitätsklinikum Münster

EMAH-Aufbaukursus
Münster, 2.-3.12.2012
Westfälische
WilhelmsUniversität Münster
EMAH: Stellenwert der medikamentösen
(antiarrhythmischen) Therapie
Prof. Dr. Dr. h.c. Günter Breithardt
Universitätsklinikum Münster
Department für Kardiologie und Angiologie;
Kompetenznetz Vorhofflimmern
Münster / Germany
ODER
Westfälische
WilhelmsUniversität Münster
Was davon übrig geblieben ist
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
Ein Blick in die Leitlinien genügt ?M
Eur Heart J 2010
43 Seiten, aber nur …
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
Ein Blick in die Leitlinien genügt ?M
99 Seiten, aber nur …
WWU Münster
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
Ein Blick in die Leitlinien genügt??
Clin Res Cardiol 2008
21 Seiten, aber nur….
•  AVSD: Rhythmusstörungen: Behandlung je nach Art. Antiarrhythmische
Behandlung (medikamentös; Ablation) oder Schrittmacherversorgung.
•  Ebstein: Rhythmusstörungen werden medikamentös oder durch
Katheterablationsverfahren behandelt.
•  Fallot: Behandlung von Herzrhythmusstörungen nach den üblichen
Kriterien
Arrhythmien bei EMAH: ESC Leitlinie 2010
●  Häufige Ursache von Morbidität und Letalität; Hauptgrund für
Krankenhausaufnahmen
●  Risikostratifizierung und Behandlung oft anders als bei
normal geformten Herzen
●  Arrhythmien können Zeichen einer hämodynamischen
Dekompensation sein
●  Das Risiko von Arrhythmien kann verstärkt werden durch die
häufig zu Grunde liegenden abnormen Kreislaufverhältnisse
●  Katheterablationen verlangen spezielle Erfahrungen und
Geschick; die Ergebnisse sind in der Regel bei EMAHs
schlechter – dennoch das bevorzugte Verfahren, wenn
möglich
●  Antiarrhythmika werden oft schlecht vertragen
www.escardio.org/guidelines
Akuter Herztod bei EMAHs
●  Der akute Herztod stellt ein besonderes Problem bei
EMAH dar
●  Fünf Defekte mit dem höchsten Risiko:
- operierter Fallot
- TGA mit Vorhofumkehr-OP
- kongenital korrigierte TGA
- Aortenstenose
- univentrikuläres Herz
●  Eine nicht anders erklärte Synkope ist ein Warnsignal
●  Trotz verschiedener Risikofaktoren gibt es bisher keine
gut evaluierten Algorithmen für die Risikostratifizierung
und die Indikation zum ICD
www.escardio.org/guidelines
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
Behandlungs-Entscheidungen bei EMAH mit
ventrikulären Arrhythmien (VES, nicht-anh. und
anhaltende VT)
Verhinderung eines rhythmusbedingten Todes
Verbesserung von Beschwerden; Verhinderung
von Rezidiven
• 
• 
Behandlungsmöglichkeiten:
Antiarrhythmika
Katheterablation
Operative Ablation
ICD Implantation
ICD plus CRT
• 
• 
• 
• 
• 
Keine prospektiven
Daten, die eine
Verhinderung des
akuten Herztodes bei
postoperativen EMAHPatienten belegen!!!
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
•  ESC 2010: “Antiarrhythmika werden häufig schlecht vertragen
wegen negativer Inotropie und anderen Nebenwirkungen. Nur
wenige Daten zu ihrer Sicherheit und Wirksamkeit.”
Dies ist Folge
• der zu Grunde liegenden strukturellen und funktionellen
Störungen nach meistens palliativen Eingriffen, wodurch die
Neigung zu Proarrhythmie steigt, und
• der häufigen Sinuknotenfunktionsstörungen, vor allem nach
Vorhof-Operationen (Mustard, Senning oder Fontan)
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
The efficacy of antiarrhythmic agents
remains poorly studied in adult congenital
heart disease, with little data regarding
dosing and toxicity.
S Abadir, P Khairy, Progr Cardiovasc Dis 2011; 53: 281-292
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
• Given the lack of evidence-based
recommendations specific to adults with CHD,
pharmacological options are often dictated by
general guiding principles.
• These include considerations regarding
  systemic ventricular dysfunction,
  sinus node disease,
  impaired AV conduction,
  negative inotropic effects,
  potential proarrhythmic effects, and
  extracardiac side-effects.
S Abadir, P Khairy, Progr Cardiovasc Dis 2011; 53: 281-292
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
•  Atrial tachyarrhythmias may be poorly
tolerated in patients with
  single ventricles,
  systemic right ventricles,
  cyanosis,
  pulmonary hypertension,
  ventricular dysfunction,
  multiple or high-risk accessory pathways, and/
or rapid atrial conduction
S Abadir, P Khairy, Progr Cardiovasc Dis 2011; 53: 281-292
Patienten nach Fontan Operation
●  Antiarrhythmische Therapie:
  Verlust des Sinusrhythmus kann eine hämodynamische
Verschlechterung bewirken; eine anhaltende Tachykardie sollte
als Notfall eingestuft werden.
  Die elektrische Kardioversion stellt die Hauptbehandlungsform
bei Tachykardien dar, da Medikamente oft unwirksam sind.
  Amiodaron kann Rezidive verhindern, hat aber viele
Nebenwirkungen. Sotalol stellt eine Alternative dar.
  Niedrige Schwelle zur Behandlung mittels Katheterablation; diese
Arrhythmien sind aber schwer zu behandeln.
  Antitachykarde Vorhofschrittmacher können hilfreich sein.
  Falls AV-Stimulation erforderlich, dann epikardiale Elektroden.
  Das Auftreten von Arrhythmien sollte zu einer hämodynamischen
Evaluation führen.
www.escardio.org/guidelines
ESC Guidelines for the management
of grown-up congenital heart disease 2010
WWU Münster
• ASD: Without repair or with repair after 40 years, atrial
fibrillation becomes more common and may require
antiarrhythmic therapy (little is known about ablative
therapy in this setting).
ESC Guidelines for the management
of grown-up congenital heart disease 2010
WWU Münster
Zyanotische Patienten:
• Der Sinusrhythmus sollte aufrecht erhalten werden,
wenn immer möglich.
• Die antiarrhythmische Therapie sollte individuelle
eingesetzt werden (Medikamente, Ablation, epikardiale
Dchrittmacher/ICD).
• Die antiarrhythmische Therapie ist sehr schwierig bei
dieser Patientengruppe.
• Antiarrhythmika sollten besonders vorsichtig
eingesetzt und im allgemeinen stationär eingeleitet
werden.
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
Flecainide
Encainide
WWU Münster
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
Pediatric Electrophysiology Group
• Data from 36 institutions of 579 young pts who
received encainide or flecainide for treatment of
 SVT (encainide 86 pts, flecainide 369 ps) or
 ventricular arrhythmias (encainide 21 pts, flecainide 103 ps)
• to assess the frequency of proarrhythmia, cardiac
arrest and death during therapy
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
• Similar with regard to
 efficacy (flecainide 71.4%, encainide 59.8%) and
 rate of proarrhythmic responses (flecainide 7.4%;
encainide 7.5%)
• However, patients on encainide
 more frequently experienced cardiac arrest (encainide
7.5% vs. flecainide 2.3%, p < 0.05) or
 died during treatment (encainide 7.5% vs. flecainide 2.1%;
p < 0.05)
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
44 pts with adverse event
29 pts with underlying
congenital or “functional” heart
disease
19 of 32 pts on flecianide
10 of 12 pts on encainide
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
Plasma flecainide (ng/ml)
Plasma concentrations of flecainde in 26 pts experiencing adverse events
1000
800
600
400
200
0
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
• Detailed data on 44 pts experiencing one or more
adverse events
• Patient age, previous drug trials, concomitant
therapy and days of inpatient monitoring were
similar for pts receiving encainide or flecainide
• However, echo LV shortening before treatment was
lower among pts receiving encainide (0.23 + 0.09)
than among those receiving flecainide (0.34 + 0.06,
p < 0.05)
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
• Cardiac arrest (12 patients) and deaths (13
patients) occurred predominantly among pts with
underlying heart disease, particularly among pts
receiving flecainide for supraventricular
tachycardia (8.3% vs. 0.3%, p < 0.001)
• 15 pts with an ostensibly normal heart and normal
ventricular function experienced proarrhythmia
during treatment for supraventricular tachycardia,
but only 3 of the 15 had a cardiac arrest or died
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
Conclusion
• The relatively high incidence of adverse events
should be considered when contemplating
treatment with encainide or flecainide, particularly
among pts with underlying heart disease
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
Proarrhythmia, cardiac arrest and death in young
patients receiving encainide and flecainide
WWU Münster
Fish FA, Gillette PC, Benson DW Jr. JACC 1991;18:356-65
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
Amiodarone
WWU Münster
Amiodarone treatment of critical arrhythmias
in children and young adults
WWU Münster
• Amiodarone was given to 39 young pts (35 with an
abnormal heart of whom14 pts with postoperative repair
of congenital heart disease
• Arrhythmias unresponsive to conventional treatment
• Age from 6 weeks to 30 years
  Atrial flutter in 16 pts
  VT in 14 pts
  SVT in 9 patients
• Symptomatic side effects were:
  rash (3 pts), headache (2 pts), nausea (1 pt) and peripheral neuropathy
(1 pt); 7 pts asymptomatic corneal microdeposits which normalized in
all after the drug was discontinued (sic!!!)
• No side effects in pts <10 years of age
Garson A Jr, Gillette PC, et al., JACC 1984; 4:749-55
Amiodarone treatment of critical arrhythmias
in children and young adults
WWU Münster
Follow-up: 6 mos to 3 yrs in 39 pts (data from abstract)
• 21 pts (54%) continued to take amiodarone with
complete control of arrhythmias
• 9 (23%) were no longer taking the drug
• 9 (23%) died (7 nonsudden and 2 sudden deaths)
Conclusion:
• “Amiodarone is an extremely effective treatment for
infants and children with tachyarrhythmias resistant to
conventional treatment”
Garson A Jr, Gillette PC, et al., JACC 1984; 4:749-55
Amiodarone treatment of critical arrhythmias
in children and young adults
WWU Münster
Follow-up: 6 mos to 3 yrs in 39 pts (data from Results)
• 21 pts (54%) continued to take amiodarone with
complete control of arrhythmias
• 6 pts (15%) successful but all died from progressive
heart failure (5/6 had complex end stage congenital HD)
• 4 pts (10%) symptomatic side effects, drug withdrawn
• 3 pts (8%) partially successful, all stopped amio
• 5 pts (13%) failure:
  1 died from untractable SVT after amio;
  1 pt, palliated complex cyanotic HD (29 yrs), amio for 4 days:
progressive AV-block, low cardiac output
Garson A Jr, Gillette PC, et al., JACC 1984; 4:749-55
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
Amiodarone
 is generally considered the most effective agent
but
 long-term therapy is limited by the concern for
time- and dose-dependent side-effects in young
adults.
 Thyroid dysfunction is particularly common in
women with CHD and cyanotic heart disease or
univentricular hearts with Fontan palliation (1)
(1) SA Thorne, …, J Somerville, Circulation 1999; 100: 149-54
Amiodarone-associated thyroid dysfunction: Risk factors
in adults with congenital heart disease
WWU Münster
• 92 adults (34.9 +10.2 years,16 to 60 years) with congenital HD
who had taken amiodarone for >6 months
A case-control analysis was performed, with patients
matched for duration of amiodarone therapy
36% developed thyroid dysfunction: 19 became hyperthyroid
and 14 hypothyroid
Female sex and complex cyanotic heart disease were
significant risk factors for developing thyroid dysfunction
(odds ratios, 3.0 and 7.00; P=0.04 and 0.01, resp.)
Previous Fontan-type surgery also appeared to be a risk
factor for developing thyrotoxicosis (odds ratio, 4.0; P =
0.17!!), and amiodarone >200 mg/d a risk factor for thyroid
dysfunction (odds ratio, 4.0; P = 0.60!!).
• 
• 
• 
• 
SA Thorne, …, J Somerville, Circulation 1999; 100: 149-54
Amiodarone-associated thyroid dysfunction: Risk factors
in adults with congenital heart disease
WWU Münster
Conclusions
Amiodarone-associated thyroid dysfunction is
common in adults with congenital heart disease
Women and those with complex cyanotic lesions
are at particular risk, as pts may be who have had
Fontan-type surgery or are taking >200 mg/d of
amiodarone (both n.s.!!)
Amiodarone should be used only when other
antiarrhythmics are ineffective or contraindicated.
Vigilance is required to detect and treat thyroid
dysfunction.
• 
• 
• 
• 
SA Thorne, …, J Somerville, Circulation 1999; 100: 149-54
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
Dronedarone
WWU Münster
ATHENA: No patients with congenital heart
disease included
WWU Münster
S Hohnlser, et a., ATHENA / dronedarone: NEJM 2009; 360: 668-78
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
Sotalol
WWU Münster
Efficacy and proarrhythmia of oral sotalol in
pediatric patients
WWU Münster
Mean age 7.3 years
JP Pfammatter, Th Paul, Ch Lehmann, HC Kallfelz, JACC 1995; 26: 1002-7
Efficacy and proarrhythmia of oral sotalol in
pediatric patients
WWU Münster
CAP = concealed accessory pathway
JP Pfammatter, Th Paul, Ch Lehmann, HC Kallfelz, JACC 1995; 26: 1002-7
Efficacy and proarrhythmia of oral sotalol in
pediatric patients
WWU Münster
• Sotalol was either completely (27 [66%] of 41 pts) or
partially effective (11 [27%] of 41) in 38 (93%) of 41 pts
with SV reentrant tachycardia
• In atrial flutter predominantly after operation for CHD,
sotalol was effective in 84% of pts (completely in 9 of 19
and partially in 7 of 19)
• VT was completely (3 of 11) or partially (4 of 11)
controlled in 64% of children
• Proarrhythmia occurred in seven pts (10%)
JP Pfammatter, Th Paul, Ch Lehmann, HC Kallfelz, JACC 1995; 26: 1002-7
Efficacy and proarrhythmia of oral sotalol in
pediatric patients
WWU Münster
CAP = concealed accessory pathway
JP Pfammatter, Th Paul, Ch Lehmann, HC Kallfelz, JACC 1995; 26: 1002-7
EMAH: Stellenwert der medikamentösen
antiarrhythmischen Therapie
WWU Münster
The efficacy of antiarrhythmic agents
remains poorly studied in adult congenital
heart disease, with little data regarding
dosing and toxicity.
S Abadir, P Khairy, Progr Cardiovasc Dis 2011; 53: 281-292
Oder: Viele Worte um nichts. Eine
Aufforderung zu mehr Wissen.
Vielen Dank für Ihre
Aufmerksamkeit