Atrial fibrillation in a couple: a case report
Erica Delsignore1, M Cristina Bertoncelli1, Tiziana Ciarambino2, Cecilia Politi2
1. SC Medicina Interna, Ospedale S. Andrea, Vercelli;
2. UOC Medicina Interna, Ospedale F. Veneziale, Isernia, Italy.
Received 14 January 2016; accepted 26 February 2016.
Summary. We present a case report confirming previous findings of epidemiological studies: not only does atrial fibrillation (AF) show different features between genders, related to biological differences, in terms of prevalence, clinic characteristics and complications, but there is also possibility for people of different gender to receive different treatments.
Key words: atrial fibrillation, gender, anticoagulant oral therapy.
Un caso clinico di fibrillazione atriale (di coppia)
Riassunto. Presentiamo un caso che conferma quanto già segnalato dagli studi epidemiologici: non solo la fibrillazione atriale può avere caratteristiche diverse nei due generi, legate a differenze biologiche, in termini di prevalenza, caratteristiche cliniche e complicanze, ma esiste anche la possibilità che persone di diverso genere ricevano un differente trattamento farmacologico.
Parole chiave: fibrillazione atriale, genere, terapia anticoagulante orale.
Atrial fibrillation (AF), a common cardiac arrhythmia in Western countries and Japan, not only has a different prevalence between men and women1, but, as reported in different studies, shows also sex-related difference in clinical and pharmacological treatment1,2. There is often a tendency to believe that women are protected against cardio-vascular diseases, but this wrong cultural assumption comes from a possible difficult and/or delayed diagnosis because women may show more nuanced symptomatic features that differ from those of males. We have to consider that until a few years ago women were left out from trials and studies and that the conclusions were drawn from observations on men that are not necessarily applicable to women. Moreover, women tend to underestimate their symptoms, to be more hesistant to accept medical check-ups and drug prescriptions and in general to put the care of others before themselves.
Like other cardiac pathologies, some studies have found gender differences in AF treatment, showing that at times a most conservative approach is preferred for women, while other studies have highlighted a less frequent use of oral anticoagulant therapy (OAT).
We report two cases of patients with AF who received different diagnostic and therapeutic approach.
• Male, 83 years old, F.B., former smoker, with arterial hypertension, chronic kidney disease stage III-IV, dilated cardiomyopathy (EF 35-40%), AF with good response to cardioversion in 2003. After AF relapse, OAT was started with warfarin (in 2003 CHADS2 = 3 and in 2009 CHA2Ds2-VASc = 4, with a thromboembolic risk of 5.9%/year; HAS-BLED = 2), as recommended by guidelines, and heart rate control with betablockers. Two echocardiograms were performed in 2003 and in 2009, confirming damage to the anatomic structure of the heart damage and impaired cardiac function: he presented progressive left ventricular and atrial dilatation and mitral valve and tricuspid regurgitation. He died of cardiogenic shock in 2010, few months after his first admission to our Internal Medicine Unit.
• Female, 80 years old, L.R., clinical history of arterial hypertension, hyperthyroidism, previous NSAID-related gastric bleeding, obesity, persistent AF (CHA2DS2-VASc = 4, HAS-BLED = 3), diagnosed in the cardiology unit and treated with digoxin and ASA. At the time of the first medical examination at our unit, the echocardiogram was never performed.
We calculated stroke risk with CHADS2 and CHA2Ds2-VASc at the time of the first diagnosis of AF and at the time of hospitalization at our unit respectively, and HAS-BLED was also calculated (Table 1)3,5,7,8.
Our patients had a similar risk of stroke and bleeding, but they were treated differently. Differences in HAS-BLED risk did not warrant the choice of antiplatelet therapy (with almost similar gastric bleeding rate) in the female patient, L.R..
It is amazing to note that our patients were married, had a similar age at time of diagnosis, lived in the same home, with the same primary care physician and were not conscious of having a similar yet differently treated disease, despite guidelines (Tables 2A, 2B)4,6-8.
The woman accepted to start OAT only after her spouse’s death, because before then she thought she did not have time to take care of her own health, but only that of her sick husband.
She started a novel oral anticoagulant a year ago, because she was in therapeutic range for insufficient time.
AF is the most common cardiac arrhythmia and independent risk factor for thromboembolism. Periodic guidelines are drawn up concerning rhythm/rate control and OAT in order to avoid thromboembolic stroke9.
Some studies have highlighted differences between genders in AF treatment and underutilization of OAT, despite the higher risk of stroke in women9, who also receive frequently more conservative treatment10. However, reports are not consistent.
Indeed, while the Canadian AF Registry quoted underutilization of OAT in 2001 (as many other reports), in 2013 the ATA-AF Study did not find differences and, in the same year, according to the FALP observational study, the male gender was negatively correlated to OAT11,12.
According to the Euro Heart Survey on AF, women frequently were asymptomatic or had AF with atypical symptoms (dyspnea, chest pain, dizziness and fatigue), while men displayed mainly typical symptoms (palpitations and syncope). In overall symptomatic cases, the authors did not find differences between genders, but the treatment was more conservative in asymptomatic women or women with atypical symptoms: they received electrical cardioversion less frequently (rate control was preferred), but no differences were found in OAT, in contrast with other studies10,13. Women showed higher stroke risk, according to the Framingham and ATRIA studies that reported a high risk of thromboembolism if they did not receive OAT14.
Compared to the men, several potential mechanisms could contribute to prothrombotic milieu and thromboembolic risk in women, above all in menopause: estrogen decline-related upregulation in the production of inflammatory cytokines, alterations in the vascular and myocardial structure, impaired endothelial function, increased platelet aggregation and increase in arterial pressure, pulse pressure and pressure variability9.
Female gender should be an independent risk factor for thromboembolic stroke in AF and has been added to CHA2DS2VASC by the Birmingham 2009 Schema and employed in the ESC 2010 guidelines8,15. The NEMESIS Study has demonstrated that women have more severe stroke symptoms and worse post-stroke impairment as opposed to men9.
In the ATRIA study, OAT was more protective for women with AF than among men with the same disease and they had a similar rate of major bleeding14, but several studies have shown suboptimal time in the therapeutic range compared to men9.
These results, as well as our case report, confirm gender differences, despite guidelines for the management of patients with AF and similar stroke risk.
This demonstrates an underutilization of OAT among women, which should be considered instead with greater attention in this gender, although inequality of treatment or therapeutic choices should not always be considered evidence of discrimination: at times, it may prove to be beneficial to women. For instance, rate control versus rhythm control could improve outcomes in female gender10.
Gender medicine, which applies the idea of the “difference between genders”, aims at providing the best treatment to everybody, whether men or women, and at achieving better gender-related therapy.
1. Inoue H, Takashi Nozawa T. Sex-related differences in the risk factor profile and medication of patients with AF recruited in J-TRACE. Circ J 2010; 74: 650-4.
2. Humphries K, Kerr CR. New-onset AF: sex differences in presentation, treatment and outcomes. Circulation 2001; 103: 2365-70.
3. Gage BF, Waterman AD. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285(22): 2864-70.
4. Camm JA, Lip GYH. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J 2012; 33: 2719-47.
5. Pisters R, Lane DA. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation. Chest 2010; 138 (5): 1093-100.
6. Fuster V, Rydén LE. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary. Circulation 2001; 104: 2118-50.
7. Fuster V, Rydén LE. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation. Circulation 2006; 114; e257-e354.
8. Camm JA, Kirchhoff P. Guidelines for the management of AF. The Task Force for the Management of AF of the European Society of Cardiology (ESC). Eur Heart J 2010; 31: 2369-429.
9. Cove CL.; Albert CM. Female sex as an independent risk factor of stroke in AF. Thrombosis and Haemostasis 2013; 111: 385-91.
10. Dagres N, Nieuwlaat R. Gender-related differences in presentation, treatment and outcome of patients with AF in Europe. JACC 2007; 49 (5): 572-7.
11. Gussoni G, Di Pasquale G. Decision making for oral anticoagulation in AF: the ATA-AF Study. Eur J Intern Med 2013; 24 (4): 324-32.
12. Campanini M, Frediani R. Real-world management of AF in Internal Medicine units: the FADOI “FALP” observational Study. J Cardiovasc Med 2013; 14: 26-34.
13. Rienstra M, Van Veldhuisen DJ. Gender related differences in rhytm control treatment in persistent AF. Data of the Rate Control versus Electrical Cardioversion (RACE) study. J Am Coll Cardiol 2005; 46: 1298-306.
14. Fang MC, Singer DE. Gender differences in the risk of ischemic stroke and peripheral embolism in AF: The ATRIA Study. Circulation 2005; 112(12): 1687-91.
15. Lip GYH, Nieuwlaa R. Refining clinical risk stratification for predicting stroke and thromboembolism in AF using a novel risk factor-based approach. The Euro Heart Survey on AF. Chest 2010; 137(2): 263-72.