ORIGINAL ARTICLE

Antithrombotic Strategies in Atrial Fibrillation. The XIX CONAREC Registry

Estrategias antitrombóticas en fibrilación auricular. Registro CONAREC XIX

 

VALENTÍN C. ROEL¹, JUAN A. MOUKARZEL², EZEQUIEL J. ZAIDEL3, MATÍAS A. GALI⁴, WALTER DA ROSA⁵, RODOLFO LEIVA⁶, CAROLINA CICERO⁷, JORGE THIERER^{MTSAC, 8}, on behalf of the Argentine Council of Residents in Cardiology

SEE RELATED ARTICLE: Rev Argent Cardiol 2015;83:183-184. http://dx.doi.org/10.7775/rac.v83.i3.6645

Received: 01/05/2015 - Accepted: 03/11/2015

Address for reprints: Dr. Valentín C. Roel - Consejo Argentino de Residentes de Cardiología. Sociedad Argentina de Cardiología - Azcuénaga 980 -(C1115AAD) Ciudad Autónoma de Buenos Aires - e-mail: valsis@hotmail.com

Argentine Council of Residents in Cardiology (CONAREC)

^MTSAC Full Member of the Argentine Society of Cardiology

¹ Chief Resident Hospital Durand (CABA)
² Chief Resident Fundación Favaloro (CABA)
³ Chief Resident Sanatorio Güemes (CABA)
⁴ Chief Resident Hospital Eva Perón (ex Castex) (Buenos Aires Province)
⁵ Chief Resident Hospital Alta Complejidad (Formosa)
⁶ Chief Resident Hospital del Centenario (Rosario)
⁷ Resident, Hospital Lagomaggiore (Mendoza)
⁸ Head of Heart Failure Hospital Universitario CEMIC (CABA)

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ABSTRACT

background: Atrial fibrillation (AF) represents the most common sustained arrhythmia. Treatment has evolved since the last survey performed in our setting, with a marked trend towards the use of anticoagulation therapy, and the development of new anticoagula-tion drugs. However, Argentina lacks updated data about antithrombotic therapy or the use of new oral anticoagulants (NOAC).
Objective: The aim of the study was to assess antithrombotic strategies in AF patients admitted for cardiovascular causes in centers with cardiology residency.
Methods: Between September and November 2013, 927 patients with at least one episode of atrial fibrillation within the last 12 months and hospitalized for cardiovascular causes in centers with cardiology residency were enrolled in the study.
results: Median values (interquartile range) of CHADS2 and CHA2DS2-VASc and HASBLED scores were: 2 (1-3), 3 (2-4) and 1 (1-2), respectively. At admission, only 54% of patients with history of AF without contraindication and CHADS2 1 (n=253) received anticoagulation therapy; 89% with dicoumarinic agents and only 26.5% in the therapeutic range. At discharge, anticoagulation rates increased up to 70%, and including all patients without contraindication, 59.74% received anticoagulation therapy at discharge. As-pirin as single strategy was used in 26% of patients. The major reasons for not prescribing anticoagulants included contraindications (36%), social limitations (21%) and unknown reasons (14.8%). Stroke [OR 2.18 (95% CI 1.02-4.67); p=0.04], age [OR 1.01 (95% CI 1-1.03); p=0.009], hypertension [OR 1.54 (95% CI 0.99-2.41); p=0.05], heart failure [OR 1.68 (95% CI 1.1-2.55); p<0.01] and severe ventricular dysfunction [OR 4.99 (95% CI 1.71-14.55); p=0.003] were independent predictors of anticoagulation. High level of educa-tion was a predictor for the use of NOAC (OR 1.84, 95% CI 1.08-3.14).
Conclusions: The population of this survey performed in centers with cardiology residency has moderate thromboembolic risk and low bleeding risk. The rate of oral anticoagulation increased during hospitalization and high level of education was associated with the indication of NOAC.

Key words: Atrial Fibrillation - Anticoagulation - Hemorrhage - Stroke

RESUMEN

introducción: La fibrilación auricular (FA) representa la arritmia sostenida más frecuente. Desde el último relevamiento en nuestro medio, la concepción del tratamiento ha cambiado, con una marcada tendencia hacia la anticoagulación de los pacientes, y han surgido nuevas drogas anticoagulantes. No obstante ello, no existen datos actualizados en la Argentina sobre el tratamiento antitrombótico ni del uso de nuevos anticoagulantes orales (NACO).
Objetivos: Evaluar las estrategias antitrombóticas en la FA en pacientes internados por una causa cardiovascular en centros con residencia de cardiología.
Material y métodos: Entre septiembre y noviembre de 2013 se registraron 927 pacientes con al menos un episodio de FA en los 12 meses previos e internados por una causa cardiovascular en centros con residencia de cardiología.
resultados: las medianas (rango intercuartil) de CHADS2, CHA2DS2-VASc y HASBLED fueron de 2 (1-3), 3 (2-4) y 1 (1-2), respectivamente. Al ingreso solo recibían anticoagulantes el 54% de los pacientes con antecedente de FA sin contraindicación y CHADS2 1 (n = 253), con dicumarínicos el 89% y solo el 26,5% en rango terapéutico. En ellos, la tasa de anticoagulación al alta subió al 70%. Incluyendo a todos los pacientes sin contraindicación al alta, el 59,74% recibió anticoagulación. La aspirina como única estrategia fue empleada en el 26%. Los motivos para no anticoagular fueron contraindicaciones (36%), limitaciones sociales (21%) y no aclarados en el 14,8%. Fueron predictores independientes de anticoagulación en pacientes sin contraindicaciones: el accidente cerebrovascular [OR 2,18 (IC 95% 1,02-4,67); p = 0,04], la edad [OR 1,01 (IC 95% 1-1,03); p = 0,009], la hipertensión arterial [OR 1,54 (IC 95% 0,99-2,41); p = 0,05], la insuficiencia cardíaca [OR 1,68 (1,1-2,55); p < 0,01] y la disfunción ventricular grave [OR 4,99 (IC 95% 1,71-14,55); p = 0,003]. El alto nivel educativo fue predictor de NACO (OR 1,84, IC 95% 1,08-3,14).

Conclusiones: La población de este registro realizado en centros con residencia de cardiología presenta un riesgo tromboembólico moderado y un riesgo hemorrágico bajo. Durante la internación se observó un aumento de las tasas del uso de anticoagulantes orales y el nivel educativo fue un factor asociado con la indicación de NACO.

Palabras clave: Fibrilación auricular - Anticoagulación - Hemorragia - Accidente cerebrovascular

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abbreviations

Abbreviations
AF Atrial fibrillation
AFL Atrial flutter
ECG Electrocardiogram
NOAC New oral anticoagulants

 

INTRODUCTION

Atrial fibrillation (AF) is the most frequent sustained arrhythmia. According to international registries it is estimated that about 1-2% of the world population suffers from this disease and its prevalence is even higher with increasing age, reaching 15% in the popu-lation over 80 years of age. (1, 2)

The presence of AF doubles mortality rate (3, 4) even adjusted for other causes, with a fivefold increase in the risk of stroke, which is often fatal. (5)

Due to the progressive increase in life expectancy, the prevalence of AF in the overall United States population could reach 5.6 billion people by 2050. (1)

In our setting, 13 years have elapsed since the publication of the last survey on AF management. (6) Thereafter, the concept of treatment has changed, and with the development of new anticoagulant drugs there is a marked trend towards patient anticoagula-tion. Moreover, ablation has gained a predominant role in the treatment.

The benefit of oral anticoagulation with vitamin K inhibitors for the prevention of thromboembolic events has been clearly demonstrated, with approxi-mately 64% of stroke reduction and a clear relation-ship between adherence to treatment, time in thera-peutic range and events. (7)

However, Argentina has no updated data on the characteristics of patients with A F, management strategies and oral anticoagulation.

Furthermore, new oral anticoagulants (NOAC) have emerged as an interesting option to consider in certain populations of patients with A F. Therefore, there is need of epidemiological data in the general population beyond large randomized trials.

The main aim of the XIX CONAREC registry is to survey the current status of AF in Argentina, focusing on the antithrombotic approach

METHODS

The XIX CONAREC registry is a multicenter, cross-sectional

observational study conducted in cardiology services with residency affiliated to the Argentine Council of Residents in Cardiology (CONAREC). Patients ≥18 years hospitalized for cardiovascular causes and presenting with documented AF and/or atrial flutter (AFL) or a previous history of these conditions in the past 12 months (surface ECG, Holter, te-lemetry) were included in the study. Patients with AF/AFL in the postoperative period of cardiac surgery were excluded from the study. The primary end-point sought to identify the antithrombotic strategies adopted by the treating physicians during hospitalization in the cardiology service or coronary care unit. The secondary end-point sought to detect the strategies adopted to control rhythm and heart rate. Patient recruitment was consecutively performed from September 16 to November 16, 2013, and follow-up was limited to hos-pitalization. No patient personal data was registered.

Data collection and validation

Data collection for each patient was obtained through personal interviews during hospitalization and was in charge of a cardiology resident.

Data were loaded online through the www.conarec.org page in an electronic case report form (eCRF) specially de-signed with unique access via an individual password. Data were immediately and automatically incorporated into the central database.

The information was evaluated every 15 days and the officer in charge of the center was contacted in case of incon-sistencies. Definitions have been previously published (8-9). The analysis of CHADS2, CHA2DS2-VASc thrombotic event and HASBLED bleeding risk scores was independently per-formed from their constitutive variables. Classification of AF type as a function of time of evolution and therapeutic strategy was independently adjudicated as defined in the protocol.

Cross-auditing was randomly performed to 20% of cent-ers and those presenting with a loading rate <1 patient/ month were excluded from the study.

statistical analysis

Patients with AFL were excluded from the analysis. Discrete variables are presented as percentage and continuous variables as mean±standard deviation if the distribution was normal or as median and interquartile range if they were not normal. Variables were compared using Student's t test, Wilcoxon test, chi -square test or Fisher´s exact test, as ap-propriate.

A multiple logistic regression analysis was performed to determine which factors were independently associated with indication for anticoagulation and another to assess novel anticoagulant predictors. Variables that in the univariate analysis were associated with events with p <0.10 were in-corpporated in the model. A p value <0.05 was considered as statistically significant and the Epi Info 2000® software package was used for statistical analysis.

Ethical considerations

The protocol was revised and approved by the Argentine So-ciety of Cardiology Ethical Board

RESULTS

Patient Characteristics

The study included 927 AF patients from 59 centers, distributed in the following regions: Buenos Aires/ CABA 55%, Center 28%, Argentine North 12%, New Cuyo 4% and Patagonia 1%. Patient baseline charac-teristics are listed in Table 1. Median age was 73 years (64-81) and 59% of patients were men. Atrial fibrilla-tion showed no valvular etiology in 93% of cases. His-tory of stroke was found in 9.8% of cases (84% with ischemic etiology) and transient ischemic attack in 3%. The estimated CHADS2 score for thromboem-bolic risk had a median of 2 (1-3) and the CHA2DS2-VASc score a median of 3 (2-4). In 9.5% of cases, no risk factor was detected by CHADS2 and this value was reduced to 4% using CHA2DS2-VASc. The risk of bleeding assessed by HASBLED presented a median of 1 (1-2).

Hospitalization

Patients had medical coverage insurance in 85% of cases: social security in 49%, prepaid coverage in 21% and PAMI in 15%. Eleven percent of patients had not completed primary education. The most frequent reasons for hospitalization were AF in 37% of cases, decompensated heart failure in 31% and coronary ar-tery disease in 8.5%, with a median hospital stay of 4 days (1, 5-7). Transthoracic echocardiography was performed during hospitalization in 83% of patients, with estimated moderate to severe left ventricular systolic dysfunction in 25% of cases; 12% of patients underwent transesophageal echocardiography.

Eighty-seven percent of patients presented with symptoms (66% with EHRA III/IV). According to Gallagher´s AF classification, (10) first episode was found in 42% of cases, paroxysmal in 13.5%, persis-tent in 17.5% and permanent in 27%. Overall mortal-ity was 6% and 0.4% in patients exclusively hospital-ized for A F. In the admission electrocardiogram 85% of patients presented with A F, 13% with sinus rhythm and 2% with other ECG patterns.

antithrombotic strategy

Patients with a history of non-valvular AF without

Table 1. Baseline population characteristics

age, years*	73	64-81
We¡ght, kg*	80	70-90
Heart rate, bpm*	106	76-140
	n	%
Female gender	382	41.2
Valvular aF	60	6.5
F¡rst epísode of AF	261	41.6
Hypertensíon	724	78.4
Diabetes	153	16.9
AMI	140	15.3
Stroke	89	9.8
TÍA	23	2.9
Heart faüure	326	35.6
Moderate-severe LVEF	193	24.87
peripheral vascular disease	114	12.6
Uver dysfunctíon	22	2.4
alcohol consumption	73	8
renal failure	138	15.1
Cáncer	74	8.1
Dyspepsía	72	7.9
anemia	156	17
Labüe INR	32	4.2
Major bleedíng	27	3
Mild bleedíng	40	4.4
Hemorrhagíc stroke	5	0.6
CHADS2*	2	(1-3)
CHA2DS2-VASc*	3	(2-4)
HASBLED*	1	(1-2)

AF: Atrial fbrilation. AMI: Acute myocardial infarction. TIA: Transient ischemic attack. LVEF: Left ventricular ejection fraction. INR: Interna-tional Normalized Ratio. *median (interquartile range)

contraindications and with CHADS2≥1 (n=253) were under anticoagulant therapy in 54% of cases (median CHADS2=2 [1-3]). They were mostly treated with di-coumarinic agents (89%, only 26.5% of which were in the therapeutic range on admission); the remaining 11% were treated with NOAC (dabigatran at doses of 110 and 150 mg every 12 hours, and rivaroxaban). At the time of this registry apixaban was not marketed.

In this selected population, anticoagulation rate increased significantly between admission and dis-charge from 54% to 70%, respectively [OR 1.98 (1.35-2.91)]; p <0.05] (Figure 1).

In 59.74% of cases, patients without contraindi-cations received anticoagulant therapy at discharge (CHADS2 score of 0, 1 and ≥2 in 6.1%, 31.9% and 61.7% of these patients, respectively). Percutaneous atrial FiBrillation XiX ConareC registry / Valentín C. roel et al. on behalf of ConareC

Fig. 1. Antithrombotic strate-gies in patients with history of atrial fbrillation with no contraindications and CHADS₂> 1 (n=253). Signifcant increase of strategies, including antico-agulant agents, observed after hospitalization in a center with cardiology residency. (OR 1.98; p<0.01). OAC= Dicou-marinc agents. ASA=Aspirin, NOAC=New oral anticoagulants.

closure of left atrial appendage was made only in 0.4% of cases. The independent predictors associated with the use of anticoagulation in patients without con-traindications were stroke, age, hypertension, heart failure and severe ventricular dysfunction (Table 2).

In our registry, the overall rate of ASA use at dis-charge was 26%, while only 23 patients (2.6%) re-ceived triple antithrombotic scheme.

new oral anticoagulants

Six percent of patients with history of AF received NOAC treatment. Several factors were associated with use of NOAC such as age, gender, renal dysfunc-tion, weight, embolic risk, risk of bleeding, educa-tional level, health coverage and concomitant use of aspirin. In the multiple logistic regression analysis (Table 3), adjusted by all the other factors, only high educational level was predictor of NOAC use (OR1.84, 95% CI 1.08-3.14). A strong association was also found between prepaid coverage and high educational level, the latter prevailing in the multivariate analysis. At discharge, the overall rate of NOAC was 16%, distrib-uted in rivaroxaban (6.7%), and dabigatran 150 mg (5.7%) and 110 mg (3.5%).

no anticoagulation

Excluding patients who died in hospital, 351 patients (40%) were discharged without anticoagulation (Figure 2). The reasons were: contraindications (36%), social limitations (21%), and patient decision (8%). Nineteen percent of patients did not receive antico-agulation owing to low embolic risk score, and in 15% no reason was found for not indicating anticoagula-tion. A trend for not using anticoagulant therapy was observed in patients with coronary stent (see Table 2). No anticoagulation due only to old age was described as the most frequent relative contraindication.

table 2. Multiple logistic regression analysis of predictors for anticoagulant use
	Odds Ratio	95% Cl	'
Severe LVEF	4.99	1.71-14.55	0.003
Stroke	2.18	1.02-4.67	0.04
Heart faüure	1.68	1.10-2.55	0.01
Hypertensíon	1.54	0.99-2.41	0.05
renal failure	1.47	0.72-2.98	0.27
Diabetes	1.13	0.64-2.01	0.66
Female gender	1.07	0.7-1.63	0.72
age	1.01	1-1.03	0.009
Stent	0.59	0.31-1.11	0.10

LVEF: Left ventricular ejection fraction

supplementary data

Figure 3 shows anticoagulant therapy at discharge as a function of CHA2DS2-VASCc

DISCUSSION

The XIX CONAREC registry describes the updated characteristics of patients with AF hospitalized in centers with cardiology residency in Argentina. More-over, this is the first Argentine registry including pa-tients treated with NOAC.

As the registry was conducted in cardiology wards, it included patients with more comorbidities and with at least moderate thromboembolic risk as evidenced by median values of 2 and 3 in the CHADS2 and CHA2DS2-Vasc scores, respectively. However, antico-agulation rate in patients with prior AF and antico-agulant therapy indication was only 54%, increasing significantly to 70% at discharge. These results are superior to those obtained previously in our country

 

table 3. Predictors of new anti-coagulant indication

	OR	Uní vai ¡ate analysis 95% Cl	P	Múltiple regression analysis OR 95% Cl p
Female gender	0.54	0.32-091	0.01
CHA2DS2-VASc		.	<0.01
HASBLED			<0.01
Severe LVEF	1.91	1.06-3.57	0.018
Aspírin	0.52	0.30-0.88	<0.01
H¡gh educatíonal level	1.82	1.1-3.01	<0.01	1.92 1.13-3.26 0.015
old age	0.42	0.24-0.68	<0.01
SevereCRF	0.37	0.11-1.23	0.04

The only predictor in the multiple regression model was high educational level (complete secondary or uni-versity education). In a second adjustment after inclusion of health coverage, only educational level remained signifcant (see text). LVEF: Left ventricular ejection fraction. CRF: Chronic renal failure

Fig. 2. Main causes for not indicating oral anticoagulation (n=351). CI= contraindication.

5%
13%		■ Relative Cl
^		^ D Social limitations
i		^| D CHADS7=0
15% ^		f ■ Not specifed
^		V D Absolute Cl
^H 20%	¥	' D Patient decisión

Fig. 3. Supplementary material. Anticoagulation at discharge according to the CHA2DS2Vasc score. OAC: Anticoagulation

Anticoagulation rate according to the CHA2DS2Vasc score

90% 1

70% / 60%

0123406789 ■ NO OAC OAC

with a total rate of 48.5% reported patients with anti-coagulant use in the PENFACRA (6) registry, and are consistent with international data collected in regis-tries such as the Euro Heart Survey on Atrial Fibril-lation (11) but lower than in exclusively ambulatory

AF registries such as the Orbit AF study. (12) This marks a clear trend favoring the use of antithrombotic strategies in AF in our country following current rec-ommendations. On the other hand it shows the im-portance of hospitalization in a cardiology service, as previous registries have reported the relevant involve-ment of a cardiologist at the moment of indicating an-ticoagulant treatment compared to the intervention of a clinical or general practitioner. (6).

According to the present registry, the independent predictors to indicate anticoagulation in Argentina were: previous stroke, age, history of heart failure and left ventricular ejection fraction impairment, all of them contributing to thromboembolic risk scores used in daily practice, showing coherence and ration-ality in antithrombotic indications consistent with in-ternational data.

Of note, only 26% of patients with dicoumarinic anticoagulants were in the therapeutic range on ad-mission, considering that this is a determinant factor of thromboembolism, bleeding and even death in pa-tients treated with anticoagulant therapy (13). This result should be viewed with caution as it is a unique and defined value on patient admission and data were not collected during hospitalization or ambulatory fol-low-up. Most patients (49%) received acenocoumarol as vitamin K antagonist, whose pharmacokinetics and interactions are different from warfarin used in most registries and clinical trials.

In the last years, with the introduction of NOAC, the spectrum of possibilities has expanded turning the decision of indicating antithrombotic treatment even harder. As in the case of dicoumarinic agents, the rate of NOAC use increased after hospitalization in a car-diology ward. These drugs might be useful in specific groups, such as patients with difficulties in adherence or understanding the dicoumarinic scheme. However, the only independent predictor of NOAC at discharge was a high educational level, revealing a relationship between this variable and prepaid health coverage. It is possible that the current cost of these drugs has a clear influence on prescription and that this distribu-tion might change with time according to the econom-ic and social situation.

Interestingly, despite the high thromboembolic risk, this was not a population at high risk of bleed-ing, presenting a median HASBLED of 1. This should favor the rate of anticoagulation. However about 35% of patients with no absolute contraindications and with CHA2DS2-Vasc≥2 and CHADS2≥1 are not an-ticoagulated despite having a net clinical benefit as demonstrated from these risk strata in favor of anti-coagulation (14). Among the major causes of non-an-ticoagulation are social limitations and the patient's decision, barely modifiable from the cardiologist´s position.

However, excluding these two groups, there re-mains a considerable percentage of non-anticoagu-lated patients without absolute contraindications, old age being the most common cause in this group. As an isolated datum old age should not be a contraindica-tion to anticoagulation, since the reduction of stroke risk exceeds the risk of bleeding (8-15), but there are different variables of a subjective nature such as fra-gility or unstable gait that in everyday practice lead to contraindicate anticoagulants.

limitations

The XIX CONAREC registry exclusively included hospitalized patients evaluated in cardiology services. This entails three drawbacks; firstly the described population may not be representative of the general population of patients with AF in our country; sec-ondly there is no patient follow-up data and thirdly it does not provide data on ambulatory patients exclu-sively with A F, who usually have fewer comorbidities, and hence, less risk. On the other hand, the inclusion of patients hospitalized for cardiovascular causes in-dicates that it is a heterogeneous population with a relatively high overall mortality not attributable ex-clusively to A F.

COnClUsiOns

The XIX CONAREC registry provides updated infor-mation on the indication of oral anticoagulation ther-apy and the first results on the use of NOAC. The sur-veyed population has a moderate thromboembolic risk and low bleeding risk. Regarding previous data, the rate of anticoagulation in patients with high throm-boembolic risk has increased. In turn, hospitalization in a center with cardiology residency has significantly raised the indication of anticoagulation in the popula-tion studied.

Nevertheless, a significant percentage of patients in Argentina are not anticoagulated without a clear justification.

Conficts of interest

None declared

(See author´s conflicts of interest forms in the web / Supplementary Material)

REFERENCES

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3. Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener HC, et al. Outcome parameters for trials in atrial fibrillation: executive summary. Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eur Heart J 2007;28:2803-17. http://doi.org/cst44w

4. Stewart S, Hart CL, Hole DJ, McMurray JJ. A population based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/ Paisley study. Am J Med 2002;113:359-64. http://doi.org/cd3bgv

5. Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Fram-ingham study. Neurology 1978;28:973-7. http://doi.org/2s9

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APPENDIx

Main centers and researchers

Center	Researcher
bUEnOs airEs
Centro de alta Complejidad pte. peron	Camilo pulmari
Clinica ima adrogue	Fernando Barone
Clinica san nicolas - san nicolas	nahuel guadagnoli
Hospital Castex eva peron	Dario igolnikof
Hospital el Cruce - Florencio Varela	pilar anoni
Hospital Universitario austral	maria laura ayerdi
Caba
Fundación Favaloro	Federico Zeppa
Htal. aeronáutico Central	alejo orellano
Htal. aleman	Juliana marin
Htal. argerich	Juan soumolou
Htal. Cesar milstein	gonzalo miranda
Htal. Churruca	marina Baglioni
Htal. Durand	soledad Vizzarri
Htal. italiano	Fernando Cohen
Htal. naval	alberto gobelet
Htal. militar Central	Jorgelina Dorado
Htal. ramos mejia	Juan Carlos ruffno
Htal. rivadavia	Javier Juan miguel
Htal. santojanni	nelcy prado
instituto Cardiovascular de Buenos aires	luciano Battioni
instituto Cardiovascular Denton Cooley	Victor nuñez
sanatorio Colegiales	Cristian suarez
sanatorio güemes	matias grieco
sanatorio Julio mendez	ignacio garrido
sanatorio mitre	Diego Crippa
sanatorio sagrado Corazón	Carlos luis gonzalez
COrDOba
Clinica Chutro	alejandro Delgado
Clinica reina Fabiola	Carolina ingaramo
Clinica Velez sarsfeld	Carlos segura
Htal. aeronautico Córdoba	ana grassani
sanatorio allende	Jose Werenitzky
COrriEntEs
Htal. José de san martin	José romano
instituto Juana Cabral	pablo aguirre
FOrMOsa
Hospital de alta Complejidad Formosa	sebastián ghibaudo
JUJUY
sanatorio ntra. sra. Del rosario	augusto Barboza
la riOJa
Htal. enrique Vera Barros	mauro Diaz

Center	Researcher
instituto del Corazon - inCor	lisandro ivan metelsky
MEnDOZa
Htal. Central de mendoza	pablo giganti
Htal. el Carmen - godoy Cruz	soledad tejera
Htal. luis lagomaggiore	Jennifer Cozzari
sociedad española de socorros mutuos	saimon sgarioni
nEUQUEn
Htal. Castro rendon	lorena patricia Heine
salta
Htal. san Bernardo	Julio nuñez
san JUan
Hospital marcial Quiroga	alejandro peñaloza aviles
santa FE
Clínica de nefrologia y enfermedades	maria Jose Diez
Cardiovasculares
Hospital Clemente alvarez (rosario)	Celeste giuli
Hospital español de rosario	ivan gribaudo
Hospital italiano garibaldi de rosario	luciano Calvente
Hospital provincial del Centenario	rodolfo leiva
(rosario)
Hospital provincial de rosario	marcela galuppo
instituto Cardiovascular de rosario	miguel Hominal
instituto De Cardiologia Dr. sabathie	marcos Cicerchia
(rosario)
ipC - sagrada Familia	mauro storani
sanatorio de la mujer	Claudio marigo
sanatorio Diagnóstico y tratamiento	Victor alfonso
sanatorio nosti (rafaela)	pamela reyes
sanatorio mayo	gonzalo Costa
sanatorio los alerces (rosario)	Carolina navarro
sanatorio los arroyos (rosario)	romina Deganutto
sanatorio parque (rosario)	sabrina Juliá
sanatorio rosendo garcia Uom (rosario)	Valeria Cabrol
sanatorio san gerónimo	santiago Vicario
sanatorio santa Fe	marianela Colombo
tUCUMan
instituto de Cardiologia srl	pilar Haurigot
Centro privado de Cardiologia	Jorge Carminati

AUDIT: Marcela Galuppo, Ignacio Cigalini, Cristian Pazos, Abigail Cueto, Evaristo Castellanos,GabrielTissera, German Albrecht, Liliana Gasparini, Paula Ramos, Anabela Seta, Adrián Picech, Jennifer Cozzari, Ezequiel Besmalinovich.