[SCD-FORUM] 107E Female patient, 30 years old. Dr. Perez Riera

[SCD Symposium]

Dear Dr Yunlong Xia from China Very interesting case. Your young woman has or had:
1)      Strong familiar positive background for sudden cardiac death in first degree relatives( four members!!!! ) The family have disease of the conduction system because her father and one of her aunt have received pacemaker implantation
2)      Clearly she has a diffuse disease of intra atrial (bradycardia,  atrial standstill, after pacemaker implantation, her left atrium is standstill., paroxysmal atrial tachycardia/fibrillation) and intraventricular conduction system;
3)      Clinical class III: Syncope;
4)      Pulmonary arterial hypertension with dilatation of right and left atrium and right ventricle.
5)  Typical familial Atrial standstill picture.
Atrial standstill is a rare arrhythmogenic condition characterized by the absence of electrical and mechanical activity in the atria, transient or persistent, and complete or partial. 
It can be Secondary to (1)
1)      Primary or idiopathic
2)      Sporadic;
3)      Familial: autosomal dominant. A few cases of familial forms of primary atrial standstill have been described in the literature. Mutation in the cardiac Na+ channel gene SCN5A associated with relatively rare genotypes for two connexin 40 polymorphisms has been reported. Rarely is associated with Brugada syndrome(BrS): Takehara et al, reported a case of BrS with ST elevation in the right precordial and inferior leads accompanied by atrial standstill and VF. Atrial standstill and J wave elevation were provoked by procainamide. Genetic analysis revealed a missense mutation (R367H) in SCN5A. The resultant mutant Na+ channel was nonfunctional when expressed heterologously in Xenopus oocytes. The study suggests that genetic defects in SCN5A may be associated with atrial standstill in combination with BrS (2). My dearest friend Dr Hanno Tan wrote: “various gating changes that ultimately result in reduced Na current may elicit BrS, conduction disease, atrial standstill, and sinus node disease. Emerging insights now also link these gating defects to enhanced arrhythmia susceptibility in common, acquired, disease. For instance, AP prolongation in CHF may be explained by increased persistent Na current. Of note, recent studies have also linked Na current reduction to structural cardiac defects, notably cardiac fibrosis, dilated cardiomyopathy and, possibly, ARVD/C. Clearly, these observations highlight the cardiac Na channel as an interesting target for novel therapy strategies”(3).
4)      Secondary to
4-1)           Ebstein's anomaly: atrial standstill, atrial paralysis and atrio-ventricular block are an uncommon association with Ebstein's anomaly (4) In this case is possible problem in right cameras.
4-2)           Emery-Dreifuss muscular dystrophy (X-linked);
4-3)           Kugelberg-Welander syndrome (autosomal recessive);
4-4)           Myocardial infarction;
4-5)           Amyloidosis. 

 Diagnosis of atrial standstill include:
1)      Bradycardia on ECG
2)      Absence of P waves in any lead of the standard ECG
3)      Atrial paralysis;
4)      Atrial dilatation;
5)      Eventually atrial fibrillation;
6)      Eventually atrial flutter;
7)      Slow junctional escape rhythm;
8)      Syncope or Morgagni-Adams-Stokes episodes( near 50% of cases);
9)      High prevalence of thrombotic complications ( as her father)
10)  Cardiac enlargement due primarily to atrial enlargement seems to be a common feature of both the complete and partial form of the familial persistent atrial standstill syndrome (5).
11)  Atrial standstill associated with syncope, dilated cardiomyopathy, and SCD (6).

Your young patient and  some family members seem have all of this before elements. 
Treatment
1)      Anticoagulation;
2)      IECA
3)      Diuretic
4)      Pacemaker implantation;
5)      Atrial flutter: treated by His-bundle ablation(7)


You ask: Is it possible that her left atrium function could recover later? Answer:  No because it is a progressive familial disease.
 
You wrote:  If necessary we can encourage the patient to do more test. Yes you must encourage the patient and family members to do the genetic test.
 
References
1)       Marini M, Arbustini E, Disertori M.Atrial standstill: a paralysis of cardiological relevance Ital Heart J Suppl. 2004;5:681-686.
2)       Takehara N, Makita Nm Kawabe J et al. A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill. J Intern Med. 2004; 255:137-142. 
3)       Tan H. Sodium channel variants in heart disease: expanding horizons. J Cardiovasc Electrophysiol. 2006;17 Suppl 1:S151-S157. 
4)       Carballal J, Asensio E, Hernandez R. et al. Ebstein's anomaly, atrial paralysis and atrio-ventricular block: an uncommon association. Europace. 2002; 4:451-454. 
5)       Disertori M, Guarneiro M, Vergara G, et al.Familial endemic persistent atrial standstill in a small mountain community: review of eight cases. Eur Heart J. 1983;4:354-361
6)       Fazelifar AF, Arya A, Haghjoo M, et al. Familial atrial standstill in association with dilated cardiomyopathy. Pacing Clin Electrophysiol. 2005;28:1005-1008. 
7)       Balaji S, Till J, Shinebourne EA, Familial atrial standstill with coexistent atrial flutter. Pacing Clin Electrophysiol. 1998;21:1841-1842. 
 
 
All the best
Andrés Ricardo Pérez Riera
Chief of Electro-Vectocardiology Sector of the Discipline of  Cardiology, ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC) - Santo André -  Sao Paulo - Brazil. Rua Sebastiao Afonso  885 - Zip Code: 044417-100- Jardim Miriam   S.P  Brazil- Phone: 5504-6243  Fax: 5506-0398.

________________________________________
Dear Dr. Perez Riera and other colleagues

Last week I have met a special case, and here I want to get help from you.

Female, 30 years old. She came into my hospital because of black spell and syncope for 2 weeks. The ECG shows atrial standstill and junctional/ventricular escape rhythm of 36, with atrium suspected to be retrograde excited (Fig 1***). After injection of 1 mg atropine for 10-20 min, the escape rate was only slightly increased to 50-55 bpm with standstill atrium (Fig 2***). After that isoprotorenol was intravenous infused to keep escape rate 50-55 bpm. Occasionally, paroxysmal atrial tachycardia/fibrillation and ventricular premature complex could be observed during monitoring, and AV was found not to be 1:1 conducted (Fig. 3***, P wave is clear especially on Lead V1). The routine blood test, heart enzyme, thyroid test and autoimmune system test are all inside normal range. Echocardiography reports the significant tricuspid annulus dilation, with tricuspid insufficiency, medium pulmonary artery hypertension, intra vena cava dilation (IVC 20), right system dilation (RA 52 X 61, RV 21), left atrial dilation (LA 43 X 57) and normal ventricular wall motion.

After observation for 2 days, the bradycardia continued and a DDDR pacemaker was implanted, with atrium lead in right appendage. During implantation the atrium was demonstrated to be retrograde activated, but no further EP test was performed. After implantation, the P wave could be only seen positively on lead V1, whereas in other leads it can’t be clearly observed (Fig 4***). Later echocardiography showed relatively weak right atrium motion, and left atrium standstill. Warfarin was administered to her with INR 1.8-2.5. 

SEE ECGs
http://www.scd-symposium.org/files/yunlong1.jpg
http://www.scd-symposium.org/files/yunlong2.jpg
http://www.scd-symposium.org/files/yunlong3.jpg
http://www.scd-symposium.org/files/yunlong4.jpg

Family histories: 

Two years ago the lady got pregnant (during that period her ECG is normal) and then had a baby boy with normal ECG. She has a younger brother and a younger sister with normal ECG now. 

The lady’s father has 7 brothers and sisters, in which 4 of them died before 40 years old due to heart attack without clear diagnosis, because of the limited medical conditions in their hometown. Her father and one of her aunt have received pacemaker therapy around 20 years ago, and the patient did not know their clear diagnosis. Her father died from cerebral embolism later and her aunt also died later with uncertain reasons. 

She don’t know more about her family history now because most of her other relatives are scattering in China and living far away from her, and cannot be reached so easily. We are still encouraging her to find more of her family members.

My question is:

1.     Have you met such kind of familial bradycardia with atrial standstill and tricuspid annulus dilation before? Progressive Cardiac Conduction Defects (PCCD) or the Lev-Lenègre disease usually causes RBBB/LBBB or even complete AVB with sclerosis of the left "cardiac skeleton" (Mitral annulus abnormal). However, besides the sinus and/or atrial conduction defect, in this case right “cardiac skeleton” seems to be sclerosis. 
2.     The patient did not accept the cardiac Computed Tomography due to the cost. She doesn’t want EP test and myocardial biopsy now. In my hospital we cannot have a genetic test, either. What should we do now? If necessary we can encourage the patient to do more test.
3.     After pacemaker implantation, her left atrium is standstill. Is it possible that her left atrium function could recover later?

Thanks for your time.

All the best

Yunlong Xia
Department of Cardiology
First Affiliate Hospital of 
Dalian Medical University
Dalian, China. 116011
Email: yunlong.xia at gmail.com