Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCFDh8FZXZdD8k6CsP9fr3yFpS0066-782X2017000700005S0066-782X201700500810310.5935/abc.20170064Original ArticleThromboembolism and bleeding risk scores and predictors of cardiac death in a population with atrial fibrillationSilvaRose Mary Ferreira Lisboa daSilvaPollyana Ardavicius eLimaMarcos CorreiaSant'AnnaLívia TanureSilvaTúlio CorrêaMoreiraPedro Henrique VilelaGandraRobert MoreiraCavalcantiTúlio RamosMourãoPlínio Henrique VazUniversidade Federal de Minas GeraisMGBrazilUniversidade Federal de Minas Gerais, MG - BrazilUniversidade Federal de Minas GeraisMailing Address: Rose Mary Ferreira Lisboa da Silva, Avenida Alfredo Balena, 190, sala 246, Centro, Postal Code 30130100. Belo Horizonte, MG - Brazil. E-mail: roselisboa@cardiol.br
Contribuição dos autores
Conception and design of the research: Silva RMFL. Acquisition of data: Silva RMFL, Silva PA, Lima MC, Sant'Anna LT, Silva TC, Moreira PHV, Gandra RM, Cavalcanti TR, Mourão PHV. Analysis and interpretation of the data: Silva RMFL, Silva PA, Lima MC, Sant'Anna LT, Silva TC, Moreira PHV, Gandra RM, Cavalcanti TR, Mourão PHV. Statistical analysis: Silva RMFL. Writing of the manuscript: Silva RMFL. Critical revision of the manuscript for intellectual content: Silva RMFL.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
25052017072017109010513030620162201201709032017This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractBackground:
Atrial fibrillation (AF) is a common arrhythmia, with risk of systemic embolism and death. It presents rheumatic etiology in up to 32% of developing countries, whose anticoagulation and evolution data are scarce.
Objectives:
to determine the predictors of cardiac death considering the clinical profile, thromboembolism and bleeding scores of patients with AF of a single center, with high prevalence of rheumatic heart disease.
Methods:
302 patients with AF were studied, mean age 58.1 years; 161 women; 96 pts with rheumatic etiology. Patients underwent clinical and laboratory evaluation, measurement of risk scores and the mean follow-up of 12.8 months.
Results:
174 were using warfarin. The averages of the HAS-BLED and ATRIA scores were 1.4 and 1.2, respectively. Percent time in therapeutic range of international normalized ratio was 45.8%. Thirty patients (9.9%) had cardiac death and 41 had some type of bleeding due to warfarin. By univariate analysis, there was statistical significance between cardiac death and permanent AF, blood pressure, systolic dysfunction, R2CHADS2, CCS, EHRA and HAS-BLED. There was no association with valvular AF. By multivariate analysis, systemic arterial and pulmonary artery pressures, classification CCS and systolic dysfunction showed statistical significance.
Conclusions:
There was no association between cardiac death and valvular AF. Independent predictors of cardiac death were low measures of blood pressure, higher score CCS classification and the presence of systolic ventricular dysfunction.
Atrial fibrillation (AF) affects 2% of the population, its prevalence increases with age, reaching the rate of 15% in those with 80 years, and half of the patients with AF present age equal to or greater than 75 years.1,2 Beyond this epidemiological importance, this arrhythmia is associated with worsening of quality of life and tolerance to efforts, thromboembolic phenomena, hospitalization, heart failure (HF), and double the mortality rate.1,3-6 AF increases the risk of stroke by 5 times, which also increases with age, with a risk of 1.5% in those between 50 and 59 years of age and 23.5% in the 80-89 age group.1,3 Among patients with AF rheumatic valve etiology, the risk is 17 times that of the general population and 5 times in relation to patients with non-valvular AF.7 Due to the risk of thromboembolism, oral anticoagulation is indicated for these patients. However, this therapy has complications, with an annual incidence of bleeding of 2.1 per 100 individuals, resulting in a mortality rate between 13 and 33%.8,9 Therefore, adequate stratification of the risk of thromboembolism and bleeding is mandatory.
Rheumatic valvulopathy is a disease with a high prevalence in developing countries, yet it is still neglected.10 In AF, this etiology presents different percentages, from 2.2% in developed countries to 31.5% in those in development.11 There is scarce current data on the treatment and evolution of patients with AF and rheumatic heart disease.11-13 Therefore, the objectives of this study are to analyze the clinical profile, thromboembolism and bleeding scores of patients with AF from a single university institution and verify the predictive variables of cardiac mortality.
Methods
It is an observational, longitudinal and prospective study. The population consisted of 302 consecutive patients with AF, who came from the outpatient clinic and the Cardiology nursing ward and who accepted to participate in the study. Patients were selected over a one-year period. The research project was approved by the Ethics and Research Committee of the institution and all patients signed the Informed Consent Term. Patients underwent clinical evaluation, 12-lead electrocardiogram, transthoracic echocardiography, and clinical pathology exams. The diagnosis of AF was made by electrocardiogram at the time of symptoms or by virtue of irregular heart rhythm. At the time of inclusion in the study, the following scores were calculated for all patients: American College of Cardiology (ACC),7 HAS-BLED and ATRIA bleeding scores,14,15 and severity ratings of symptoms and impact in the quality of life of the Canadian Cardiovascular Society (CCS)16 and the European Heart Rhythm Association (EHRA),1 and the Framingham score17 for predicting stroke (F1) and for predicting death or stroke (F2). On the other hand, the CHADS2, R2CHADS2 and CHA2DS2-VASC1,14,18 scores were calculated only for non-valvular AF cases. The clinical intercurrences were recorded as thromboembolic events, hemorrhagic events and cardiac death.
For the analysis of the data, the SPSS program (Statistical Package for Social Science) version 14.0 was used. The results were expressed in numbers and proportions, for categorical variables, and in measures of central tendency (mean or median) and dispersion (standard deviation) for continuous variables. The Mann-Whitney and chi-square or Fisher tests were used to compare the differences between the continuous and categorical variables, respectively. Survival analysis was performed using the Kaplan-Meier curve, considering the occurrence of cardiac death. Logistic regression analysis was used by the Stepwise method, with the dependent variable being the occurrence of cardiac death, considering the variables with p ≤ 0.10 in the univariate analysis. The level of statistical significance adopted was 5%.
ResultsPopulation characteristics, thromboembolism and bleeding scores
The casuistry consisted of 302 patients who were followed for 12.8 ± 11.8 months (from 15 days to 66 months), of which 161 (53.3%) were female. The mean age was 58.1 ± 15.1 years, ranging from 18 to 92 years. Clinical data, calculated scores and echocardiographic values are shown in Table 1. They had systolic ventricular dysfunction, defined as the ejection fraction lower than 50%, 112 patients (37.1%). Valvular heart disease was of rheumatic etiology in 96 patients. The valvular dysfunction of rheumatic etiology was moderate/important mitral stenosis in 34 patients, moderate/severe mitral regurgitation in 10, double mitral lesion in 13, and 39 patients had been submitted before to the implantation of a prosthesis in the mitral position, being 10 with mechanical prosthesis . Three patients had mitral valve prolapse with moderate/severe insufficiency. Among patients with non-valvular AF were not included patients with valvular morphological alterations.
Clinical characteristics and echocardiographic parameters of patients
Variable
Number (proportion and variation)
Femenine gender (%)
161 (53%)
Age (years)
58.1 ± 15.1 (18-92)
BMI (Kg/m2)
25.1 ± 5.5 (14.9-55.0)
Paroxysmal AF
87 (28.8%)
Persistent AF
45 (14.9%)
Permanent AF
170 (56.2%)
Etiology
Valvular Heart Disease
99 (32.8%)
Dilated cardiomyopathy
95 (31.5%)
Hypertensive cardiomyopathy
85 (28.1%)
Others (ischemic without ventricular disfunction, congenit, pericarditis constrictive, Brady-Taqui syndrome)
11 (3.6%)
Isolated AF
12 (4.0%)
Previous thromboembolism
62 (20.5%)
HR (bpm)
81 ± 19 (34-180)
SBP (mmHg)
121 ± 22 (60-200)
DBP (mmHg)
75 ± 13 (30-120)
ACC Score
Low risk
25 (8.6%)
Moderate risk
133 (44.0%)
High risk
143 (47.4%)
CHADS2
1.7 ± 1.1 (0-5)
R2CHADS2
2.5 ± 1.7 (0-7)
CHA2DS2-VASc
2.9 ± 1.8 (0-8)
F1 (%)
11.8 ± 8.8 (4-54)
F2 (%)
29.7 ± 21.4 (7-95)
CCS
2.6 ± 1.1 (0-4)
EHRA
2.7 ± 0.9 (1-4)
LA (mm)
50.7 ± 10.0 (30-84)
LVDD (mm)
55.5 ± 10.4 (33-86)
LVSD (mm)
40.6 ± 12.9 (17-81)
PSAP (mmHg)
43.6 ± 13.8 (10-101)
LVEF (Teicholz)
51.6 ± 17.3 (12-85)
BMI: body mass index; HR: supine heart rate; bpm: beats per minute; SBP: supine systolic blood pressure; DBP: supine diastolic blood pressure; ACC: American College of Cardiology; Framingham score for prediction of stroke (F1) and prediction of death or stroke (F2); CCS: Canadian Cardiovascular Society; EHRA: European Heart Rhythm Association; AE: anteroposterior diameter of the left atrium; LV: left ventricle; LVDD: LV diastolic diameter; LVSD: LV systolic diameter; PSAP: pulmonary artery systolic pressure; EF: ejection fraction.
Clinical pathology examinations at the time of inclusion of the patients showed the following mean values: creatinine of 1.2 ± 1.1 mg/dL (ranging from 0.3 to 11.4), creatinine clearance by the Cockroft formula And Gault of 72.2 ± 36.4 mL/min (between 4.4 and 233.7), serum sodium of 137.4 ± 4.2 (120.0 to 150.0) mmol/L and serum potassium of 4.2 ± 0.6 (1.3 to 6.3) mmol/L.
At the time of inclusion in the study, 174 patients (57.6%) were using warfarin. The HAS-BLED and ATRIA scores presented the mean values of 1.4 ± 1.1 and 1.2 ± 1.5 (median of 1.0), respectively. In 58 patients (19.2%), the HAS-BLED was ≥ 3 and in 14 patients (4.6%) the ATRIA was high risk.
Eighty patients were on antiarrhythmic medication (4 on sotalol, 11 on propafenone and the rest on amiodarone).
Clinical follow-up and survival curves
Patients who presented with electrolytic and metabolic disorders were treated according to their disorders. There was no interference of the researchers regarding the approach and therapies adopted by the attending physicians. For heart rate control in those patients with persistent or permanent AF, beta-blockers, or calcium channel antagonists (verapamil or diltiazem) and/or digoxin were used.
During clinical follow-up of 12.8 ± 11.2 (between 15 days and 66 months), 181 (59.9%) patients used warfarin. The International Normalized Ratio (INR) fraction within the therapeutic range (TTR) was calculated to be 45.8 ± 27.6% (between zero and 100%), and 22.9% of the patients evolved with TTR ≥ 60 %. The mean scores of CHADS2 and CHA2DS2-VASC among patients who did not use and those who used warfarin were 1.8 versus 1.6 (p = 0.22) and 3.2 versus 2.6 (p = 0, 12), respectively.
Thirty patients (9.9%) died from cardiac cause and 41 (22.6%) presented some type of hemorrhage due to the use of warfarin. The causes of cardiac death were: HF in 25 patients (83.3%), sudden cardiac death in 3 (10%) and thrombosis in a mechanical valve prosthesis in 2 (6.6%). Only 6 patients (2%) had a new nonfatal thromboembolic event, and 2 were not in regular use of warfarin. The comparison of the studied variables between the patients with and without cardiac death were shown in Table 2. There was no influence of the use of antiarrhythmic and the evolution to cardiac death (16.7% in antiarrhythmic use had cardiac death and 27.5 % in antiarrhythmic use did not present with cardiac death, p = 0.14).
Comparison of the means and proportions of the variables among the group of patients who attended without and with cardiac death
Variables
Group without CD (n = 272)
Group with CD (n = 30)
Valor p
Age (Years)
58.7 ± 15.1
53.7 ± 13.8
0.14
Femenine gender
146 (53.6%)
15 (50.0%)
0.59
BMI (Kg/m2)
25.3 ± 5.3
24.2 ± 6.3
0.13
Permanent AF
146 (53.7%)
24 (80.0%)
0.01
Valvular AF
93 (34.1%)
6 (20.0%)
0.11
HR (bpm)
81.0 ± 19.0
80.3% ± 16.7
0.93
SBP (mmHg)
123.7 ± 20.8
102.0 ± 20.1
< 0.0001
DBP (mmHg)
75.7 ± 13.2
68.1 ± 13.0
0.004
LA (mm)
49.7 ± 9.4
57.9 ± 12.0
0.001
LVDD (mm)
54.7 ± 9.8
64.3 ± 12.3
< 0.0001
LVSD (mm)
39.5 ± 12.2
52.2 ± 14.7
< 0.0001
PASP (mmHg)
42.3 ± 13.3
51.3 ± 12.8
< 0.0001
LVEF (%)
53.2 ± 16.4
37.0 ± 18.4
< 0.0001
Creatinine (mg/dL)
1.2 ± 1.1
1.4 ± 0.6
0.004
Creatinine Clearance (mL/min)
72.8 ± 37.2
57.5 ± 26.5
0.01
Sodium (mmol/L)
137.9 ± 3.9
134.3 ± 4.5
< 0.0001
Potassium (mmol/L)
4.2 ± 0.5
4.1 ± 0.8
0.23
Varfarine use
149 (54.7%)
19 (63.3%)
0.37
TTR
126 (46.3%)
13 (42.3%)
0.66
BP
57 (21.0%)
11 (36.3%)
0.10
CCS
2.5 ± 1.1
3.1 ± 1.0
0.01
EHRA
2.7 ± 0.9
3.2 ± 0.9
0.02
High risk ACC
130 (47.7%)
9 (30.0%)
0.10
CHADS2
1.7 ± 1.2
1.5 ± 0.7
0.60
R2CHADS2
2.4 ± 1.7
3.0 ± 1.1
0.02
CHA2DS2–VASC
2.9 ± 1.8
2.6 ± 1.4
0.59
F1 (%)
12.0 ± 8.6
8.5 ± 5.3
0.03
F2 (%)
30.1 ± 22.0
26.2 ± 14.1
0.90
HAS-BLED
1.4 ± 1.1
1.8 ± 0.9
0.01
ATRIA
1.2 ± 1.6
1.0 ± 1.1
0.68
CD: cardiac death; BMI: body mass index; HR: supine heart rate; Bpm: beats per minute; SBP: supine systolic blood pressure; DBP: supine diastolic blood pressure; Pts: patients; ACC: score of the American College of Cardiology; Framingham score for prediction of stroke (F1) and prediction of death or stroke (F2); CCS: Canadian Cardiovascular Society; EHRA: European Heart Rhythm Association; LA: anteroposterior diameter of the left atrium; LVDD: LV diastolic diameter; LVSD: LV systolic diameter; PSAP: pulmonary artery systolic pressure; EF: ejection fraction; LV: left ventricle; TTR: fraction of the RNI values (international normalized ratio) within the therapeutic range; BP: bleeding patients.
Among patients who died due to heart failure, 24 (80%) had permanent AF (p = 0.02 by the log rank test (Mantel-Cox), 95% confidence interval between 39.7 and 47.7). Using the Kaplan-Meier curve and considering as a prognostic basis the occurrence of cardiac death, survival curves were constructed in relation to the following variables: baseline heart disease, presence of systolic ventricular dysfunction and stratification of the score R2CHADS2 (low risk: score of 0 and 1, intermediate risk: 2 and 3, high risk: ≥ 4). Twenty-two patients (73.3%) who progressed to cardiac death had dilated myocardiopathy, 5 rheumatic heart valve disease and 3 hypertensive heart diseases. The Mantel-Cox test was applied to compare the curves. In relation to systolic ventricular dysfunction, the odds ratio was 8.1 (p < 0.0001) (95% confidence interval: 3.2-20.7). The data are plotted in Figures 1, 2 and 3. There was no difference in survival curves regarding the HAS-BLED, EHRA and CCS classification.
p <0.0001 Kaplan-Meier curve of cardiac death free survival of patients in relation to baseline heart disease.
Kaplan-Meier curve and cumulative percentage of cardiac death free survival (CD) of the patients in relation to the presence of systolic ventricular dysfunction.
Kaplan-Meier curve of free survival of cardiac death (CD) of patients in relation to the stratification of the score R<sub>2</sub>CHADS<sub>2</sub>.
Multivariate analysis
Through the multivariate analysis by Stepwise and considering the variables with p ≤ 0.10 in the univariate analysis associated with cardiac death, the variables systemic arterial pressure (systolic and diastolic), pulmonary artery systolic pressure, CCS classification and systolic ventricular dysfunction were statistically significant (Table 3).
Multivariate analysis for the dependent variable cardiac death
The characteristics of the population of the present study were distinct from records already published19,20 in relation to age, gender, and mainly regarding the proportion of patients with valvular AF, which was 32.7%. The previous registries were multicentric and performed in developed countries, with only 4.2% of patients with valvar AF, which implied in older age (71.5 and 75 years) and a higher proportion of men (60.1% and 57 %). Due to these factors, the mean of thromboembolism and bleeding scores reported in those registries were also higher, considering the increase in the prevalence of atherosclerosis and blood pressure levels with increasing age. However, the EHRA classification was similar, since 70% of patients in the European registry19 presented EHRA II or III, as well as the proportion of patients with heart failure between 21.3% and 36% in the cited registries and 31,4% in the present study.
Underutilization of oral anticoagulant is an aspect already reported in the literature, as well as subtherapeutic treatment, with low rates of TTR,21-23 with improved adherence to therapy over time, as demonstrated by the registries studies.19,20 Among patients at high risk, with a previous stroke or transient ischemic stroke, about half (ranging from 19% to 81.3%) were not treated with anticoagulants.22 In the recent published European registry19 and with a previous history of embolism in 15.5% of patients, 78% were in use of some vitamin K antagonist and 6.1% in the use of new oral anticoagulants, with 13.5% of patients with labile INRs. Accordingly, in the American registry,20 the mean TTR was 65%, with 17% of patients with INR below the therapeutic range, also showing a greater adherence to the guidelines. In the present study, although about 60% of patients used warfarin at the time of inclusion and during follow-up, one-third of the patients had AF valvular and 20.5% had a history of previous embolism, with TTR lability being observed in 77, 1% of the patients, evidencing an inadequate adherence to the treatment. This underutilization of oral anticoagulation was also verified in a survey conducted in an African country with 25.6% of patients with valvular heart disease and 34.2% with anticoagulant use among eligible patients.24
Contemporary data showed an annual mortality rate of 5.8% attributed to AF, reaching up to 8.3%, and that 57.4% of these deaths were of cardiac cause, with 77.3% of them due to HF.25 In the present study, there was 9.9% of cardiac mortality, with 83% due to heart failure, of which 80% had permanent AF. In addition, survival curves showed higher cardiac mortality among patients with systolic ventricular dysfunction, with a odds ratio of 8.1. This concomitance of AF and HF, with more than half of the patients with AF having HF and more than one third of HF patients with AF,26 translating, a vicious circle adversely influences the prognosis. Systematic review and meta-analysis have confirmed the association between mortality and systolic dysfunction in patients with AF, compared with that of patients with AF, but without systolic dysfunction, during the 2-year period.27 In addition, the permanent AF presentation was the most frequent among those with cardiac death in the European multicenter study with a one-year follow-up.25
The R2CHADS2 score was published in 201328 and is calculated by adding 2 more points to CHADS2 for patients with non-valvular AF and creatinine clearance < 60 mL/min to better stratify the risk of thromboembolic events. There are no studies on this score and cardiac mortality in patients with AF. In the study in question, the R2CHADS2 score discriminated patients who presented cardiac death, unlike the other CHADS2 and CHA2DS2-VASC scores. There is influence of age, gender, ethnicity and weight in the estimation of renal function. The Cockroft & Gault29 formula was developed with a population of 249 patients aged 18 to 92 years, which is the same range as the population of the present study. A study of 925 patients with a mean age of 69 years, ranging from 59 to 75.5 years, comparing the three formulas (Cockroft-Gault, MDRD-4 (Modification of Diet in Renal Disease Study), and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) demonstrated that the first presented greater accuracy, including comparing groups with EF <40% and ≥40%.30 Regarding the R2CHADS2 score, a recent study31 with 524 patients with AF demonstrated its utility in predicting stroke also in patients with impaired renal function, compared with the CHADS2 and CHA2DS2-VASC scores.
Although several variables were associated with cardiac death, the independent predictors of this evolution were systemic arterial pressure, CCS classification, systolic dysfunction, and pulmonary artery systolic blood pressure. A cohort study32 with patients with AF demonstrated that baseline systolic blood pressure < 120 mmHg was associated with cardiovascular mortality in those with systolic ventricular dysfunction during an average follow-up of 41 months, corroborating the results of the present study. In a systematic review with patients with HF, the highest systolic blood pressure was a favorable prognostic marker.33
Regarding the CCS classification, which was validated in terms of the quality of life of patients with AF,34 its value as an independent variable is due to its graduation, since patients with symptoms of HF secondary to arrhythmia are classified in category 4. On the other side, despite the association between the EHRA score and cardiac death, it was not a predictor of that outcome. This finding was also reported in another cohort of patients with AF, with an association between the score and hospitalization, rather than mortality.35
Pulmonary hypertension has been associated with morbidity and mortality, including in those patients with bordering systolic pressure of the pulmonary artery.36,37 Its most prevalent cause is left ventricular heart disease, with decreased or preserved ejection fraction, and mitral valvopathy. Therefore, this finding in the present study demonstrated what is already reported in the literature.
Limitations of the study
The main limitations of this study are the size of the population and the fact that it is unicentric, which does not reflect the disparities in the approach of these patients between institutions and regions. In addition, the influence of interventions such as arrhythmia reversal or ablation in patients' evolution was not investigated.
Conclusions
In the population with AF and high prevalence of rheumatic valve disease, there was an underutilization of oral anticoagulant, in spite of lower bleeding scores and thromboembolism in relation to those reported in the literature. Survival was lower in those with permanent AF, with dilated cardiomyopathy, and with high-risk R2CHADS2. The independent predictors of cardiac death were low measures of systemic arterial pressure, higher CCS scores, presence of systolic ventricular dysfunction, and pulmonary hypertension.
Sources of Funding
There were no external funding sources for this study.
Study Association
This study is not associated with any thesis or dissertation work.
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Europace. 2010;12(4):482-7.Ntep-GwethMZimmermannMMeiltzAKingueSNdoboPUrbanPBlochAAtrial fibrillation in Africa: clinical characteristics, prognosis, and adherence to guidelines in CameroonEuropace201012448248725 Lip GY, Laroche C, Ioachim PM, Rasmussen LH, Vitali-Serdoz L, Petrescu L, et al. Prognosis and treatment of atrial fibrillation patients by European cardiologists: one year follow-up of the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot registry). Eur Heart J. 2014;35(47):3365-76.LipGYLarocheCIoachimPMRasmussenLHVitali-SerdozLPetrescuLPrognosis and treatment of atrial fibrillation patients by European cardiologists: one year follow-up of the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot registry)Eur Heart J201435473365337626 Santhanakrishnan R, Wang N, Larson MG, Magnani JW, McManus DD, Lubitz SA, et al. Atrial Fibrillation begets heart failure and vice versa: temporal associations and differences in preserved vs. reduced ejection fraction. Circulation. 2016;133(5):484-92.SanthanakrishnanRWangNLarsonMGMagnaniJWMcManusDDLubitzSAAtrial Fibrillation begets heart failure and vice versa: temporal associations and differences in preserved vs. reduced ejection fractionCirculation2016133548449227 Kotecha D, Chudasama R, Lane DA, Kirchhof P, Lip GY. Atrial fibrillation and heart failure due to reduced versus preserved ejection fraction: A systematic review and meta-analysis of death and adverse outcomes. Int J Cardiol. 2016 Jan 15; 203:660-6.KotechaDChudasamaRLaneDAKirchhofPLipGYAtrial fibrillation and heart failure due to reduced versus preserved ejection fraction: A systematic review and meta-analysis of death and adverse outcomesInt J Cardiol2016011520366066628 Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, et al. 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Contribuição dos autores
Concepção e desenho da pesquisa: Silva RMFL. Obtenção de dados: Silva RMFL, Silva PA, Lima MC, Sant'Anna LT, Silva TC, Moreira PHV, Gandra RM, Cavalcanti TR, Mourão PHV. Análise e interpretação dos dados: Silva RMFL, Silva PA, Lima MC, Sant'Anna LT, Silva TC, Moreira PHV, Gandra RM, Cavalcanti TR, Mourão PHV. Análise estatística: Silva RMFL. Redação do manuscrito: Silva RMFL. Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Silva RMFL.
Potencial Conflito de Interesse
Declaro não haver conflito de interesses pertinentes.
ResumoFundamento:
A fibrilação atrial (FA) é uma arritmia comum, com risco de embolia sistêmica e morte. Apresenta etiologia reumática em até 32% dos países em desenvolvimento, cujos dados de anticoagulação e evolução são escassos.
Objetivos:
Verificar as variáveis preditoras de morte cardíaca (MC) conforme o perfil clínico, os escores de tromboembolismo e de sangramento dos pacientes com FA de uma única instituição universitária, com alta prevalência de cardiopatia reumática.
Métodos:
Foram estudados 302 pts com FA, média de idade 58,1 anos; 161 mulheres; 96 pts com etiologia reumática. Os pts foram submetidos à avaliação clínica e laboratorial, ao cálculo dos escores de risco e ao seguimento clínico médio de 12,8 meses.
Resultados:
174 pts estavam em uso de varfarina. As médias dos escores HAS-BLED e ATRIA foram de 1,4 e de 1,2, respectivamente. O cálculo da fração dos valores da razão normalizada internacional dentro do intervalo terapêutico foi de 45,8%. Houve MC em 30 pts (9,9%) e 41 apresentaram algum tipo de hemorragia em decorrência do uso de varfarina. Pela análise univariada, houve significância estatística entre MC e FA permanente, pressões arteriais, disfunção sistólica, R2CHADS2, CCS, EHRA e HAS-BLED. Não houve associação com FA valvar. Por meio da análise multivariada, a pressão arterial sistêmica e da artéria pulmonar, a classificação CCS e a disfunção sistólica apresentavam significância estatística.
Conclusões:
Não houve associação entre MC e FA valvar. Os preditores independentes de MC foram medidas baixas de pressão arterial, escores mais elevados da classificação CCS e a presença de disfunção ventricular sistólica.
A fibrilação atrial (FA) afeta 2% da população, com aumento de sua prevalência com a idade, alcançando a taxa de 15% naqueles com 80 anos, sendo que metade dos pacientes com FA apresentam idade igual ou superior a 75 anos.1,2 Além dessa importância epidemiológica, essa arritmia está associada à piora da qualidade de vida e da tolerância aos esforços, aos fenômenos tromboembólicos, à internação, à insuficiência cardíaca (IC), além de duplicar a taxa de mortalidade.1,3-6 A FA aumenta em 5 vezes o risco de acidente vascular encefálico, o qual também aumenta com a idade, com um risco de 1,5% naqueles entre 50 e 59 anos e de 23,5% entre 80 e 89 anos de idade.1,3 Entre pacientes com FA valvar de etiologia reumática, o risco é 17 vezes o da população geral e de 5 vezes em relação aos pacientes com FA não valvar.7 Devido ao risco de tromboembolismo, há indicação de anticoagulação oral para esses pacientes. Entretanto, essa terapia apresenta complicações, com uma incidência anual de sangramento de 2,1 por 100 indivíduos, resultando em uma taxa de mortalidade entre 13 e 33%.8,9 Por isso, uma adequada estratificação de risco de tromboembolismo e sangramento é mandatória.
A valvopatia reumática é uma doença com alta prevalência em países em desenvolvimento, contudo ainda é negligenciada.10 Na FA essa etiologia apresenta percentuais distintos, entre 2,2%, em países desenvolvidos, a 31,5%, naqueles em desenvolvimento.11 Há escassos dados atuais sobre tratamento e evolução de pacientes com FA e cardiopatia reumática.11-13 Por conseguinte, os objetivos deste trabalho são analisar o perfil clínico, os escores de tromboembolismo e de sangramento dos pacientes com FA de uma única instituição universitária e verificar as variáveis preditoras de mortalidade cardíaca.
Métodos
Trata-se de um estudo observacional, longitudinal e prospectivo. A população foi constituída por 302 pacientes consecutivos, com FA, provenientes do ambulatório e enfermaria de Cardiologia e que aceitaram participar do estudo. Os pacientes foram selecionados durante o período de um ano. O projeto de pesquisa foi aprovado pelo Comitê de Ética e Pesquisa da instituição e todos pacientes assinaram o Termo de Consentimento Livre e Esclarecido. Os pacientes foram submetidos à avaliação clínica, ao eletrocardiograma de 12 derivações, ao ecocardiograma transtorácico e a exames de patologia clínica. O diagnóstico de FA foi feito por meio de eletrocardiograma por ocasião de sintomas ou em virtude de ritmo cardíaco irregular. No momento da inclusão no estudo, os seguintes escores foram calculados para todos os pacientes: escore de tromboembolismo do ACC (American College of Cardiology),7 escores de sangramento HAS-BLED e ATRIA,14,15 e as classificações de gravidade dos sintomas e impacto na qualidade de vida da CCS (Canadian Cardiovascular Society)16 e da EHRA (European Heart Rhythm Association),1 e o escore de Framingham17 para predição de acidente vascular encefálico (F1) e para predição de morte ou acidente vascular encefálico (F2). Já os escores CHADS2, R2CHADS2 e CHA2DS2-VASC1,14,18 foram calculados apenas para os casos com FA não valvar. Foram registradas as intercorrências clínicas como eventos tromboembólicos, hemorrágicos e a morte cardíaca.
Para a análise dos dados, foi utilizado o programa SPSS (Statistical Package for Social Science) versão 14.0. Os resultados foram expressos em números e proporção, para variáveis categóricas, e em medidas de tendência central (média ou mediana) e de dispersão (desvio padrão) para as variáveis contínuas. Os testes de Mann-Whitney e do qui-quadrado ou de Fisher foram utilizados para comparar as diferenças entre as variáveis contínuas e categóricas, respectivamente. Foi realizada a análise de sobrevida pela curva de Kaplan-Meier, considerando-se a ocorrência de morte cardíaca. Foi utilizada a análise de regressão logística pelo método Stepwise, sendo a variável dependente a ocorrência de morte cardíaca, considerando-se as variáveis com p ≤ 0,10 na análise univariada. O nível de significância estatística adotado foi de 5%.
ResultadosCaracterísticas da população, escores de tromboembolismo e de sangramento
A casuística foi composta por 302 pacientes que foram acompanhados por 12,8 ± 11,8 meses (entre 15 dias a 66 meses), sendo 161 (53,3%) do gênero feminino. A idade média foi de 58,1 ± 15,1 anos, variando de 18 a 92 anos. Os dados clínicos, os escores calculados e os valores referentes ao ecocardiograma estão dispostos na Tabela 1. Apresentavam disfunção ventricular sistólica, definida como a fração de ejeção inferior a 50%, 112 pacientes (37,1%). A cardiopatia valvar era de etiologia reumática em 96 pacientes. A disfunção valvar de etiologia reumática foi estenose mitral moderada/importante em 34 pacientes, insuficiência mitral moderada/importante em 10, dupla lesão mitral em 13, e 39 pacientes haviam sido submetidos previamente ao implante de prótese em posição mitral, sendo 10 com prótese mecânica. Três pacientes apresentavam prolapso de valva mitral com insuficiência moderada/importante. Entre os pacientes com FA não valvar não foram incluídos pacientes com alterações morfológicas valvares.
Características clínicas e parâmetros ecocardiográficos dos pacientes
Variável
Número (proporção ou variação)
Sexo feminino (%)
161 (53%)
Idade (anos)
58,1 ± 15,1 (18-92)
IMC (Kg/m2)
25,1 ± 5,5 (14,9-55,0)
FA paroxística
87 (28,8%)
FA persistente
45 (14,9%)
FA permanente
170 (56,2%)
Etiologia
Valvopatia
99 (32,8%)
Miocardiopatia dilatada
95 (31,5%)
Cardiopatia hipertensiva
85 (28,1%)
Outros (isquêmica sem disfunção ventricular, congênita, pericardite constritiva, síndrome bradi-taqui)
11 (3,6%)
FA isolada
12 (4,0%)
Tromboembolismo prévio
62 (20,5%)
FC (bpm)
81 ± 19 (34-180)
PAS (mmHg)
121 ± 22 (60-200)
PAD (mmHg)
75 ± 13 (30-120)
Escore ACC
risco baixo
25 (8,6%)
risco moderado
133 (44,0%)
risco alto
143 (47,4%)
CHADS2
1,7 ± 1,1 (0-5)
R2CHADS2
2,5 ± 1,7 (0-7)
CHA2DS2-VASc
2,9 ± 1,8 (0-8)
F1 (%)
11,8 ± 8,8 (4-54)
F2 (%)
29,7 ± 21,4 (7-95)
CCS
2,6 ± 1,1 (0-4)
EHRA
2,7 ± 0,9 (1-4)
AE (mm)
50,7 ± 10,0 (30-84)
DDVE (mm)
55,5 ± 10,4 (33-86)
DSVE (mm)
40,6 ± 12,9 (17-81)
PSAP (mmHg)
43,6 ± 13,8 (10-101)
FEVE (Teicholz)
51,6 ± 17,3 (12-85)
IMC: índice de massa corporal; FC: frequência cardíaca na posição supina; bpm: batimentos por minuto; PAS: pressão arterial sistólica na posição supina; PAD: pressão arterial diastólica na posição supina; ACC: American College of Cardiology; escore de Framingham para predição de acidente vascular encefálico (F1) e para predição de morte ou acidente vascular encefálico (F2); CCS: Canadian Cardiovascular Society; EHRA: European Heart Rhythm Association; AE: diâmetro anteroposterior do átrio esquerdo; VE: ventrículo esquerdo; DDVE: diâmetro diastólico do VE; DSVE: diâmetro sistólico VE; PSAP: pressão sistólica da artéria pulmonar; FE: fração de ejeção.
Os exames de patologia clínica, por ocasião da inclusão dos pacientes, demonstraram os seguintes valores médios: creatinina de 1,2 ± 1,1 mg/dL (variando de 0,3 a 11,4), clearance de creatinina pela fórmula de Cockroft & Gault de 72,2 ± 36,4 mL/min (entre 4,4 e 233,7), sódio sérico de 137,4 ± 4,2 (120,0 a 150,0) mmol/L e potássio sérico de 4,2 ± 0,6 (1,3 a 6,3) mmol/L.
Por ocasião da inclusão no estudo, 174 pacientes (57,6%) estavam em uso de varfarina. Os escores HAS-BLED e ATRIA apresentaram os valores (médios) de 1,4 ± 1,1 e de 1,2 ± 1,5 (mediana de 1,0), respectivamente. Em 58 pacientes (19,2%) o HAS-BLED foi ≥ 3 e em 14 pacientes (4,6%) o ATRIA foi de alto risco.
Oitenta pacientes estavam em uso de antiarrítmico (4 em uso de sotalol, 11 em uso de propafenona e o restante em uso de amiodarona).
Seguimento clínico e curvas de sobrevida
Os pacientes que apresentavam distúrbios eletrolíticos e metabólicos foram tratados conforme seus distúrbios. Não houve interferência dos pesquisadores quanto à abordagem e terapias adotadas pelos médicos assistentes. Para controle da frequência cardíaca naqueles pacientes com FA persistente ou permanente, foram usados betabloqueadores, ou antagonistas dos canais de cálcio (verapamil ou diltiazem) e/ou digoxina.
Durante o seguimento clínico de 12,8 ± 11,2 (entre 15 dias e 66 meses), 181 (59,9%) pacientes usaram varfarina. O cálculo da fração dos valores da razão normalizada internacional (RNI) dentro do intervalo terapêutico (TTR) foi de 45,8 ± 27,6 % (entre zero e 100%), e 22,9% dos pacientes evoluíram com TTR ≥ 60%. As médias dos escores CHADS2 e CHA2DS2-VASC entre os pacientes que não usaram e aqueles que usaram varfarina foram de 1,8 versus 1,6 (p = 0,22) e de 3,2 versus 2,6 (p = 0,12), respectivamente.
Trinta pacientes (9,9%) faleceram por causa cardíaca e 41 (22,6%) apresentaram algum tipo de hemorragia em decorrência do uso de varfarina. As causas de morte cardíaca foram: IC em 25 pacientes (83,3%), morte cardíaca súbita em 3 (10%) e trombose em prótese valvar mecânica em 2 (6,6%). Somente 6 pacientes (2%) apresentaram novo evento tromboembólico não fatal, sendo que 2 não estavam em uso regular de varfarina. A comparação das variáveis estudadas entre os pacientes que cursaram com e sem morte cardíaca estão dispostos na Tabela 2. Não houve influência do uso de antiarrítmico e a evolução para morte cardíaca (16,7% em uso de antiarrítmico apresentaram morte cardíaca e 27,5% em uso de antiarrítmico não cursaram com morte cardíca, p = 0,14).
Comparação das médias e proporções das variáveis entre o grupo de pacientes que cursaram sem e com morte cardíaca
Variáveis
Grupo sem MC (n = 272)
Grupo com MC (n = 30)
Valor p
Idade (anos)
58,7 ± 15,1
53,7 ± 13,8
0,14
Sexo feminino
146 (53,6%)
15 (50,0%)
0,59
IMC (Kg/m2)
25,3 ± 5,3
24,2 ± 6,3
0,13
FA permanente
146 (53,7%)
24 (80,0%)
0,01
FA valvar
93 (34,1%)
6 (20,0%)
0,11
FC (bpm)
81,0 ± 19,0
80,3% ± 16,7
0,93
PAS (mmHg)
123,7 ± 20,8
102,0 ± 20,1
< 0,0001
PAD (mmHg)
75,7 ± 13,2
68,1 ± 13,0
0,004
AE (mm)
49,7 ± 9,4
57,9 ± 12,0
0,001
DDVE (mm)
54,7 ± 9,8
64,3 ± 12,3
< 0,0001
DSVE (mm)
39,5 ± 12,2
52,2 ± 14,7
< 0,0001
PASP (mmHg)
42,3 ± 13,3
51,3 ± 12,8
< 0,0001
FE VE (%)
53,2 ± 16,4
37,0 ± 18,4
< 0,0001
Creatinina (mg/dL)
1,2 ± 1,1
1,4 ± 0,6
0,004
Clearance de creatinina (mL/min)
72,8 ± 37,2
57,5 ± 26,5
0,01
Sódio (mmol/L)
137,9 ± 3,9
134,3 ± 4,5
< 0,0001
Potássio (mmol/L)
4,2 ± 0,5
4,1 ± 0,8
0,23
Uso de varfarina
149 (54,7%)
19 (63,3%)
0,37
TTR
126 (46,3%)
13 (42,3%)
0,66
Pts que cursaram com hemorragia
57 (21,0%)
11 (36,3%)
0,10
CCS
2,5 ± 1,1
3,1 ± 1,0
0,01
EHRA
2,7 ± 0,9
3,2 ± 0,9
0,02
ACC de alto risco
130 (47,7%)
9 (30,0%)
0,10
CHADS2
1,7 ± 1,2
1,5 ± 0,7
0,60
R2CHADS2
2,4 ± 1,7
3,0 ± 1,1
0,02
CHA2DS2–VASC
2,9 ± 1,8
2,6 ± 1,4
0,59
F1 (%)
12,0 ± 8,6
8,5 ± 5,3
0,03
F2 (%)
30,1 ± 22,0
26,2 ± 14,1
0,90
HAS-BLED
1,4 ± 1,1
1,8 ± 0,9
0,01
ATRIA
1,2 ± 1,6
1,0 ± 1,1
0,68
MC: morte cardíaca; IMC: índice de massa corporal; FC: frequência cardíaca na posição supina; bpm: batimentos por minuto; PAS: pressão arterial sistólica na posição supina; PAD: pressão arterial diastólica na posição supina; pts: pacientes; ACC: escore do American College of Cardiology; escore de Framingham para predição de acidente vascular encefálico (F1) e para predição de morte ou acidente vascular encefálico (F2); CCS: Canadian Cardiovascular Society; EHRA: European Heart Rhythm Association; AE: diâmetro anteroposterior do átrio esquerdo; DDVE: diâmetro diastólico do VE; DSVE: diâmetro sistólico VE; PSAP: pressão sistólica da artéria pulmonar; FE: fração de ejeção; VE: ventrículo esquerdo; TTR: fração dos valores do RNI (razão normalizada internacional) dentro do intervalo terapêutico; Pts: pacientes
Entre os pacientes que faleceram por causa cardíaca, 24 (80%) apresentavam FA permanente (p = 0,02 pelo teste de Log rank (Mantel-Cox), intervalo de confiança de 95% entre 39,7 e 47,7). Utilizando a curva de Kaplan-Meier e considerando como base prognóstica a ocorrência de morte cardíaca, foram construídas curvas de sobrevida em relação às seguintes variáveis: cardiopatia de base, presença de disfunção ventricular sistólica e estratificação do escore R2CHADS2 (risco baixo: pontuação de 0 e 1; risco intermediário: 2 e 3; risco alto: ≥ 4). Vinte e dois pacientes (73,3%) que evoluíram para morte cardíaca apresentavam miocardiopatia dilatada, 5 cardiopatia valvar reumática e 3 cardiopatia hipertensiva. Foi aplicado o teste de Mantel-Cox para comparar as curvas. Em relação à disfunção ventricular sistólica, a razão de chance foi de 8,1 (p < 0,0001) (intervalo de confiança de 95%: 3,2 - 20,7). Os dados estão plotados nas Figuras 1, 2 e 3. Não houve diferença quanto às curvas de sobrevida em relação aos escores HAS-BLED, EHRA e à classificação CCS.
p < 0,0001 Curva de Kaplan-Meier de sobrevida livre de morte cardíaca dos pacientes em relação à cardiopatia de base.
Curva de Kaplan-Meier e porcentagem acumulada de sobrevida livre de morte cardíaca (MC) dos pacientes em relação à presença de disfunção ventricular sistólica.
Curva de Kaplan-Meier de sobrevida livre de morte cardíaca (MC) dos pacientes em relação à estratificação do escore R<sub>2</sub>CHADS<sub>2</sub>.
Análise multivariada
Por meio da análise multivariada por Stepwise e considerando as variáveis com p ≤ 0.10 na análise univariada associadas à morte cardíaca, as variáveis pressão arterial sistêmica (sistólica e diastólica), pressão sistólica da artéria pulmonar, classificação CCS e disfunção ventricular sistólica apresentavam significância estatística (Tabela 3).
Análise multivariada quanto à variável dependente morte cardíaca
Variáveis independentes
Valor p
PAS (mmHg)
0,001
PAD (mmHg)
0,033
Classificação CCS
0,002
PSAP (mmHg)
0,006
Disfunção sistólica VE (FE < 0,50)
0,044
PAS: pressão arterial sistólica na posição supina; PAD: pressão arterial diastólica na posição supina; CCS: Canadian Cardiovascular Society; PSAP: pressão arterial sistólica da artéria pulmonar; VE: ventrículo esquerdo.
Discussão
As características da população do presente estudo foram distintas de registros já publicados19,20 em relação à idade, ao gênero, e principalmente quanto a proporção de pacientes com FA valvar, que foi de 32,7%. Os registros anteriores foram multicêntricos e realizados em países desenvolvidos, com apenas 4,2% de pacientes com FA valvar, o que implicou em idade mais avançada (71,5 e 75 anos) e maior proporção de homens (60,1% e 57%). Em virtude desses fatores, a média dos escores de tromboembolismo e sangramento reportados naqueles registros também foram maiores, considerando-se o aumento da prevalência de aterosclerose e dos níveis pressóricos com a idade. Todavia, a classificação EHRA foi semelhante, visto que 70% dos pacientes do registro europeu19 apresentavam EHRA II ou III, assim como a proporção de pacientes com insuficiência cardíaca, entre 21,3% e 36%, nos registros citados, e de 31,4% no presente estudo.
A subutilização de anticoagulante oral é um aspecto já relatado na literatura, assim como o tratamento subterapêutico, com baixas taxas de TTR,21-23 com melhoria da aderência à terapia no decorrer do tempo, como demonstrado pelos estudos de registros.19,20 Entre pacientes de risco alto, com prévio acidente vascular encefálico ou isquêmico transitório, cerca de metade (variação de 19% a 81,3%) não foram tratados com anticoagulante.22 No registro europeu, recentemente publicado19 e com história prévia de embolia em 15,5% dos pacientes, 78% estavam em uso de algum antagonista da vitamina K e 6,1% em uso dos novos anticoagulantes orais, com 13,5% de pacientes com RNI lábil. Em consonância, no registro americano,20 a média do TTR foi de 65%, com 17% dos pacientes com RNI abaixo da faixa terapêutica, demonstrando, também, uma maior aderência às diretrizes. No presente estudo, apesar de cerca de 60% dos pacientes usarem varfarina por ocasião de sua inclusão e durante seu seguimento, um terço dos pacientes apresentavam FA valvar e 20,5% com história de embolia prévia, observando-se labilidade do TTR em 77,1% dos pacientes, evidenciando uma inadequada aderência ao tratamento. Essa subutilização da anticoagulação oral também foi verificada em um inquérito feito em um país da África com 25,6% de pacientes com cardiopatia valvar e com 34,2% em uso de anticoagulante entre os pacientes elegíveis.24
Dados contemporâneos demonstraram uma mortalidade anual de 5,8% atribuída à FA, alcançando até 8,3%, e que 57,4% dessas mortes foram de causa cardíaca, com 77,3% delas por IC.25 No presente estudo, houve 9,9% de mortalidade cardíaca, com 83% por falência cardíaca, sendo que entre esses pacientes, 80% apresentavam FA permanente. Além disso, as curvas de sobrevida demonstraram maior mortalidade cardíaca entre os pacientes com disfunção ventricular sistólica, com uma razão de chance de 8,1. Essa concomitância de FA e IC, com mais da metade dos pacientes com FA apresentando IC e mais de um terço dos pacientes com IC apresentando FA,26 traduzindo, um círculo vicioso, influencia de maneira adversa o prognóstico. Revisão sistemática e estudo de meta-análise confirmaram a associação entre mortalidade e disfunção sistólica em pacientes com FA, comparada com aquela de pacientes com FA, porém sem disfunção sistólica, durante o período de 2 anos.27 Além disso, a apresentação de FA permanente foi a mais frequente entre aqueles com morte cardíaca no estudo multicêntrico europeu com seguimento de um ano.25
O escore R2CHADS2 foi publicado em 201328 e é calculado pelo acréscimo de mais 2 pontos ao CHADS2 para pacientes com FA não valvar e com clearance de creatinina < 60 mL/min, para melhor estratificação de risco de eventos tromboembólicos. Não há estudos sobre esse escore e a mortalidade cardíaca em pacientes com FA. No estudo em questão, o escore R2CHADS2 discriminou os pacientes que apresentaram morte cardíaca, diferente dos demais escores CHADS2 e CHA2DS2-VASC. Há influência da idade, do gênero, da etnia e do peso na estimativa da função renal. A fórmula de Cockroft & Gault29 foi desenvolvida com uma população de 249 pacientes com idades entre 18 e 92 anos, intervalo idêntico ao da população do presente estudo. Estudo com 925 pacientes com média de idade de 69 anos, variando de 59 a 75,5 anos, comparando as três fórmulas [Cockroft-Gault, MDRD-4 (Modification of Diet in Renal Disease Study), e CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)] demonstrou que a primeira apresentou maior acurácia, inclusive comparando grupos com FE < 40% e ≥40%.30 Quanto ao escore R2CHADS2, estudo recente31 com 524 pacientes com FA demonstrou a utilidade do mesmo para predizer acidente vascular encefálico também em pacientes com insuficiência renal importante, comparando com os escores CHADS2 e CHA2DS2-VASC.
Apesar de diversas variáveis apresentarem associação com morte cardíaca, os preditores independentes dessa evolução foram a pressão arterial sistêmica, a classificação CCS, a disfunção sistólica e a pressão arterial sistólica da artéria pulmonar. Um estudo de coorte32 com pacientes com FA demonstrou que a pressão arterial sistólica basal < 120 mmHg esteve associada à mortalidade cardiovascular naqueles com disfunção ventricular sistólica durante um seguimento médio de 41 meses, corroborando os resultados do presente estudo. Em uma revisão sistemática com pacientes com IC, a pressão arterial sistólica mais elevada foi um marcador favorável de prognóstico.33
Em relação à classificação CCS, a qual foi validada quanto à qualidade de vida de pacientes com FA,34 seu valor como variável independente deve-se à sua graduação, visto que pacientes com sintomas de IC secundária à arritmia são classificados na categoria 4. Por outro lado, apesar da associação entre o escore EHRA e a morte cardíaca, o mesmo não foi preditor daquele desfecho. Esse achado também foi reportado em outra coorte de pacientes com FA, com associação do escore à internação e não à mortalidade.35
A hipertensão pulmonar tem sido associada à morbidade e mortalidade, inclusive naqueles pacientes com pressão sistólica da artéria pulmonar limítrofe.36,37 Sua causa mais prevalente são as cardiopatias do ventrículo esquerdo, com fração de ejeção diminuída ou preservada, e a valvopatia mitral. Portanto, este achado no presente estudo demonstrou o que já está relatado na literatura.
Limitações do estudo
As principais limitações deste estudo são o tamanho da população e o fato de ser unicêntrico, o que não reflete as disparidades de abordagem desses pacientes entre instituições e regiões. Além disso, não foi investigada a influência de intervenções como reversão ou ablação da arritmia na evolução dos pacientes.
Conclusões
Na população com FA e alta prevalência de FA valvar reumática, houve uma subutilização de anticoagulante oral, a despeito de menores escores de sangramento e de tromboembolismo em relação aos reportados na literatura. A sobrevida foi menor naqueles com FA permanente, com miocardiopatia dilatada e com R2CHADS2 de risco alto. Os preditores independentes de morte cardíaca foram medidas baixas de pressão arterial sistêmica, escores mais elevados da classificação CCS, a presença de disfunção ventricular sistólica e a hipertensão pulmonar.
Fontes de Financiamento
O presente estudo não teve fontes de financiamento externas.
Vinculação Acadêmica
Não há vinculação deste estudo a programas de pós-graduação.