First-time implantation of pacemakers and prevalence of
Chagas disease at an Argentinian public hospital
JOSÉ LUIS SERRA, VICTORINO FUENTEALBA, LUIS GUZMÁN, DANIELA ROGUIER,
NÉSTOR BUSTAMANTE, SERGIO ROTTINO Y ADOLFO URIBE
Hospital Córdoba, Ciudad de Córdoba
(X5004CDT). Córdoba, Argentina. E-mail
Recibido el 04-JUL-2019 – ACEPTADO después de revisión el 17-AGOSTO-2019.
There are no conflicts of interest to disclose.
Objectives: To describe the demographics of patients submitted to a first-time implantation of a pacemaker at an Argentinian public hospital and their reasons for implantation, pacing mechanisms, and prevalence of Chagas disease. Methods: Descriptive, analytical, cross-sectional, and single-center study, in which data were collected from 624 consecutive pts from 1998 to 2013. Results: First implantations totaled 624, 57.3% were male patients. The average age was 63.8 years. Further, 81% had new generators implanted and 19% were re-sterilized. Reasons for implantation: 70% due to atrioventricular blocks (AVBs) and 30% due to sinus node dysfunction/tachycardia-bradycardia syndrome (SND/TBS). A total of 81.6% had a VVI/VVIR PM implanted. Serology for Chagas disease was positive in 58.9%. Chagasic and non-Chagasic pts had similar average ages and male prevalence. In both subgroups, AVB predominated. Non-Chagasic patients had a higher prevalence of AVB: 75.7% vs. 62.3% (p<0.002). Chagasic female patients had a higher incidence of SND / TBS compared with non-Chagasic women: 46% vs. 27% (p<0.007). Non-Chagasic male patients had the highest incidence of AVB (78%). Conclusions. The average age was 63.8 years, 57.3% of whom were male patients. The most common cause for implantation was AVB. There was a notable predominant indication for single-chamber PMs (81.6%). Nineteen percent received re-sterilized pacemakers. A high prevalence of Chagas disease was observed. Chagasic female patients had a higher incidence of SND / TBS, and more non-Chagasic male patients tended to have AVB.
Artificial pacemaker. Sterilization. Chagas disease. Public hospital.
The two main nosological entities that lead to pacemaker (PM) implant are atrioventricular block (AVB) and sinus node dysfunction/tachycardia-bradycardia syndrome (SND/TBS) [1-2].
There are different pacing modes, and according to the paced chamber(s), they may or may not preserve the atrio-ventricular (A-V) sequence. Sequential pacemaker is the device that allows to preserve A-V synchrony: AAI/AAIR, VDD, DDD/DDDR. Single-chamber pacing modes in the ventricle are not sequential: VVI and VVIR. Selecting the pacing mode according to the bradyarrhythmia causing the implant has been the object of numerous studies, and it is well known that while possible, the more physiological pacing mode should be selected if possible. The indication of pacing mode should be guided by evidence-based medicine and by the individual context of each patient, and in turn, it is often influenced by the social and financial conditions in each population and health-care institutions [2-4].
Chagas disease is a parasitic pathology, whose causing agent is the Tripanosoma cruzi, predominantly transmitted by a hematophagous insect, the Triatoma infestans, widely spread in the rural areas of Latin America [2,3,5]. It is a highly prevalent endemic in certain regions, and in Argentina, it is estimated that approximately 1,800,000 to 2,300,000 people may be carriers, though reliable data that would enable us knowing its real epidemiological impact is lacking. The region with the highest reported frequency of infected vectors is the area shared by Argentina, Bolivia and Paraguay, known as Gran Chaco [2,3,6]. The epidemiological profile has changed in recent years by controlling vector transmission in rural areas, and controlling migration phenomena of a large number of infected individuals moving to big cities, turning these parasites into an urban disease too, with the addition of new autochthonous cases by transplacental or transfusion via, or by organ transplant [2,3]. From the whole infected population, 70% remains with normal chest X-rays and ECG; while the rest evolves into the chronic cardiac form, so that in the infected population, there is 30% of chances of evolving into different degrees of heart disease.
Chronic Chagas heart disease comprises a wide range of symptoms, which go from changes in ECG, with no clinical symptoms, like ventricular repolarization alterations and His bundle blocks; to symptoms like supraventricular tachyarrhythmias, simple and complex ventricular arrhythmias, bradyarrhythmias requiring PM implant, ventricular aneurysms, dilated cardiomyopathy with heart failure and the presentation of sudden cardiac death; all of this within a very frequent framework of autonomic dysfunction [2,5,7,8].
Córdoba is the second city, in terms of number of inhabitants, of Argentina, surrounded by land at the center of the country, a medicine reference center in the province bearing the same name and also in the province of Santiago del Estero, on the north of Córdoba. In the public hospitals of Argentina, mainly the population with low income is treated; those with no formal jobs; i.e. with no medical insurance or prepaid health plans. Municipal, provincial and national states cover the expenses for such medical care.
The aims of this study were:
To write the demographic characteristics of patients undergoing first implants (FI) of PM, in the population attended in a public hospital of the city of Córdoba, from 1998 to 2013. To point out the main causes of bradycardia leading to FI. To describe the types of PM implanted. To determine the prevalence of Chagas disease. To relate the presence/absence of Chagas disease with the type of bradyarrhythmia leading to the indication of PM (SND/TBS vs AVB). To compare the latter with the demographic data between the groups of chagasic and non-chagasic patients.
MATERIALS AND METHODS Descriptive, analytic, cross-sectional and single-center study, where data were collected on 624 patients, who underwent FI of permanent PM, since January 1998 to December 2013 at the Hospital Córdoba, a public, high-complexity hospital, under the administration and direction of the state of the province of Córdoba, Argentina.
A database was prepared from a specific file designed to record the demographic and clinical data, and data on PM implant that was filled in at the time of the implant for each patient. The following variables were recorded: age, gender, new or re-sterilized generators (previously used by another, now deceased patient, for no more than 2 years; thus the generator was re-sterilized, with previous technical evaluation of its operation and battery status), VVI/VVIR pacing mode or sequential PM, reason for the implant: either SND/TBS or second- and third-degree AVB.
Within the first years of the mentioned period, the indication of the type of prosthesis to be implanted was made by the clinical cardiologist attending the patient, according to his/her personal criteria, a scenario that changed to focus mainly on the indication by the 2 first authors of this paper, who were in charge of the area of Arrhythmias and Pacemaking. Likewise, within the first years of the registry, there was more reluctance from the Public Ministry to grant sequential PMs, as they are more expensive, later agreeing about the benefits for the patients.
Serological tests were made for Chagas disease as long as it was considered necessary. The two initial methods were Elisa and hemagglutination. Serology was considered positive with reactivity in both tests, and negative in the absence of it in both. When there was mismatch, a third method was used (immunofluorescence), which if positive, confirmed the diagnosis, and if negative, ruled it out.
For the analysis of data, the software MedCalc was used, in its demo version. To compare the numerical data, the Student’s t test was used; while for the comparison of categorical data, the Chi square test was used. A p<0.05 was considered statistically significant. For the analysis of some variables of the database, the population in the study was divided by five-year periods.
Demographic analysis, type of generator, causes for the implant, pacing methods
A total of 624 FI of PM were performed over the term of the registry.
Gender: From 623 patients with surveyed gender, 57.3% were males.
Age and gender: The general average age was 63.8 years (range 19 to 96). In both genders, age averages were similar; in men 63.7 (range 19 to 96) and in women 63.5 years (range 19 to 93).
New and used generators:Table 1. The total of FI with data on this issue was 576. There were 466 (81%) new generators and 110 (19%) used and re-sterilized ones. There is no use of re-sterilized generators since 2008.
Table 1. Distribution over time of implantation of new and used (re-sterilized) generators.
Reason for the implant and gender: Both data were obtained in 612 patients, from whom 70% (428) were due to AVB. In patients with AVB, male gender was predominant (62%) versus 38% of women (p<0.002). Between the patients with SND/TBS, the distribution according to gender was similar: 51% females, 49% males.
Reason for the implant and pacing mode:Table 2. From the 612 patients whose reason to receive an implant was recorded, data were obtained on the type of pacing in 604. From them, 493 (81.6%) had VVI/VVIR PM implanted; and 111 (18.4%) sequential PM. In the group of patients with SND/TBS, 24.3% had sequential PM implanted; while between patients with AVB, only 15.8%; which shows a mild higher percentage of sequential pacing in patients with SND/TBS in comparison to those with AVB (p<0.03).
Table 2 . Pacing mode (sequential or single-chamber ventricular) according to reason for implant.
Reason for implant
VVI / VVIR PM
* p <0,03
Pacing mode according to reason for the implant and by five-year period (excluding patients that at the time of the implant presented atrial fibrillation): In Table 3, the distribution is indicated, of 347 patients with AVB who were in sinus rhythm (SR) at the time of the implant, in regard to the pacing mode used in every five-year period of the observation term: there was a marked increase in sequential pacing (41%) in the last 5-year period (2008-2013). In Table 4, the distribution is shown for 156 patients with SND/TBS, in SR at the time of the implant, and the pacing mode used in relation to each 5-year period. This group also presented in the third five-year term, an increase in the indication of sequential pacing (50%).
Table 3. Pacing mode, according to five-year period, in patients with indication by AVB,
being in sinus rhythm at the time of the implant.
Table 4. Pacing mode, according to five-year period, in patients with
indication by SND/TBS, being in sinus rhythm at the time of the implant.
Analysis according to Chagas serology
From the 624 FI, 489 patients had serology test made to determine infection by Tripanosoma cruzi. The results were 288 (58.9%) had positive serology (Chag +) and 201 (41.1%) negative serology (Chag -). In both groups, positive and negative for Chagas, there was a slight predominance of the male gender; namely, 53.8 and 54.7% respectively.
Analysis of chagasic and non-chagasic patients according to gender and age
There were no statistically significant differences in age, in the subgroups by serology and gender: in the chagasic patients, the average age was 62 years in women and 63 years in men; and in non-chagasic patients, the average age was 65 years in the female gender and 64 years in the male gender.
Reason for implant according to serology: Table 5. There were 6 patients excluded with no data and 1 non-chagasic patient with first implant due to hypertrophic cardiomyopathy. Although in both groups, AVB predominated over SND/TBS, non-chagasic patients presented a greater presence of blocks than in chagasic ones (75.8 vs 62.2%, p<0.002).
Table 5. Serology and reason for implant.
177 (62.3%) *
150 (75.8%) *
Distribution according to gender and serology of the reason for implant:Table 6. In all subgroups, AVB predominated. Male, non-chagasic patients presented a higher incidence of AVB as reason for the implant (78.18%). Chagasic women presented a higher incidence of SND/TBS (45.80%), a significantly greater prevalence between the serologically negative ones, in whom it was 26.96% (p<0.007). There were no statistically significant differences in the percentage of chagasic and non-chagasic males in regard to SND/TBS and AVB (p=0.140). When analyzing this Table from another perspective, the contribution of AVB was 177 patients (53.9%) in Chag + and 151 patients (46.03%) in serologically negative ones, which entails a similar contribution. The same did not occur with patients implanted due to SND/TBS, where Chag + patients contributed 107 patients (69.03%); while Chag – contributed 48 patients (30.9%).
Evolution of predominance of chagasic patients according to five-year periods: The percentage of chagasic patients in every 5-year term was 63.2% in the first period, 54.6% in the third one.
Table 6. Distribution according to gender and serology of reason for implant.
54,19 # 73,03 # 69,28 78,18
Num: absolute number. (* p<0.007) (# p<0.007).
Argentina is characterized by its diversity, both geographical and social, financial, cultural and sanitary. The Hospital Córdoba provides care to individuals from the province of Córdoba and nearby provinces, mainly the south of Santiago del Estero, with no financial resources, and no medical insurances or prepaid health plans. Similarly, some patients come from Bolivia, whether because they migrated years ago or are relatives to migrants.
A comparative analysis was conducted with our own data versus different publications that reported similar information on the populations having received permanent PMs.
The average age in this study (63.8 years) was less than that in several reports, among them: the Cuban study by Dr. Casola Crespo, who presented an age average of 74.6 years. In European registries and studies (from Spain, Italy, Germany and Greece), the mean age of the population was from 72 to 79 years. In these reports, just as in this study, there was a light male predominance, and AVB was the main reason for the implant [9-14]. There are not enough data to be able to explain why there was this age difference. There is no reason to hypothesize that Chagas disease lowered the average, as in the population studied, the average ages between chagasic and non-chagasic patients were similar.
In Hospital Córdoba, there was an evident predominance of single-chamber ventricular PM indication (81.6%), with higher percentage of sequential PM in patients with SND/TBS in comparison to AVB (p<0.03). There was an increase in the option of sequential PMs over time, as observed in Tables 3 and 4.
Unlike the results presented in this publication, the Spanish study showed a greater indication of sequential PMs (57.9%); highlighting in their conclusions that even this rate of indication close to 60% is low . The European registries –from Italy, Germany and France- showed a high use of sequential pacing, 66-75.4% [11,12,14]. The Greek registry showed a clear increase in the sequential pacing option over years; 26% in the first years, to subsequently reach figures greater than 50% . In a US registry (1993 to 2009) there was an evident increase in the use of dual-chamber pacing, from 62 to 82%, a very high percentage of sequential pacing in comparison to the previously mentioned studies . Unlike the European and US studies, and like the study in Hospital Córdoba, the Cuban report showed single-chamber ventricular pacing as predominant .
From what was stated above, it can be inferred that there are more indications of sequential PMs in developed countries, in comparison to countries with less financial resources. This is so, even though the different bradyarrhythmias that promote the prescription of devices remain in similar percentages in all registries.
The clinical experience of the authors of this paper and reports from literature show a predominance of advantages over drawbacks in the indication of sequential PMs, except when faced with CAVB with permanent atrial fibrillation. Numerous studies compared different modes of pacing, grouping them on the one hand, in asynchronous ventricular pacing, and on the other, in “physiological” or sequential.
There is strong evidence of less incidence of atrial fibrillation, and evidence suggesting a decrease in morbidity by heart failure in patients with atrial pacing and dual-chamber ones with predominance of ventricular sensing [16-23].
The observations on decrease of cardioembolic events and mortality vary [18-24]. It should be taken into account in this analysis, that the adverse hemodynamic effect of ventricular activation on the apex of the right ventricle has already been proven a long while ago [25,26]. It is very difficult, even with all the information available in the studies made, to be able to obtain permanent conclusions on the advantages and drawbacks of the different pacing modes, due to the variations existing between the studied populations, pacing forms and modes, percentages of ventricular pacing, follow-up terms and evaluated variables. Before the weight of the published evidence, the percentage of sequential PMs implanted at Hospital Córdoba could be considered to be low.
In relation to the type of implanted PM at Hospital Córdoba, 19% received re-sterilized generators and there were no more indications for this type of generators from 2008 forward. There were no failures in the operation of such generations in their follow-up. In regard to the implant of previously used devices, observational studies showed that reusing generators in a good operational state is safe after a proper re-sterilization [27,28].
Sandeep Patel et al, in India in year 2011 , concluded due to the good results obtained, that reused PM implant would be a safe and effective alternative for patients that require it, in countries where the possibilities of the population to have access to PM are very limited. It is a valid form to recycle completely reusable material . This practice is possible as long as the established protocols to control operation and proper sterilization guidelines are met properly. Although in the population studied, there was no regulated and prospective follow-up of patients with re-used PMs, during subsequent controls, there were no immediate or mid-term post-procedure complications, and no problem was detected with the operation of these devices, nor a greater incidence of infections related to the devices.
The consequences on morbidity and mortality in young populations affected by Chagas disease are very negative. Cardiac involvement has a significant impact on public health expense, due to requirements of PMs, cardioverter defibrillators and advanced and certainly complex treatments for heart failure [6,30,31].
Chagas disease is a significant cause of AVB and SND in Latin American countries, due to the inflammation and fibrosis of the conduction system .
This work shows a significant incidence of patients with positive serology for Chagas disease in a population with scant financial resources in the geographical center of Argentina, who have to receive a PM implant. Part of the population that comes to Hospital Córdoba comes from rural areas from the north of the city of Córdoba, or who have migrated from endemic areas close to the city. This hospital population is really not representative of the whole set of the population of the city of Córdoba, the capital city of the province, nor representative for the population of the province of Córdoba. From the 624 first implants, 489 had serology for Chagas disease made, which was positive in almost 60% (58.9%) of the studied sample.
Why was the subgroup of 135 patients with no serology for Chagas disease not tested? Hypothesizing as to why, leads to the consideration of multiple causes, among them the cases in which epidemiology was evidently negative, and/or the cause of AVB/SND being clearly attributed to another pathology: valve surgery, infarction, etc. If we assume that these 135 patients, with no serology, could have been serologically “negative” if the corresponding tests had been made, and we add the 201 with negative serology, it results in 336 patients, 70% negative vs 30% positive.
Dr. Brunetto published in the 1980s, about a group of 258 patients from another public hospital in Córdoba, with a similar population to Hospital Córdoba, 37% of whom had positive serologies .
Romero Villanueva in the 1st Virtual Conference on Chagas Disease (Federación Argentina de Cardiología 2002), revealed that in a population of 5532 individuals registered in a database of the National Institute of Retired and Pensioned Citizens, who had a PM implanted, 266 (4.8%) has positive serology for Chagas disease. Distribution was heterogeneous throughout the country, with the highest incidence (21.2%) in the provinces of Santiago del Estero, Córdoba and Catamarca; and the lowest (1.7%) in the province of Buenos Aires . This distribution is a thorough sample of the endemic area in Argentina.
Guillermo Mora et al, in 2004-2005 in Bogotá, in a descriptive, cross-sectional study, showed that in 332 patients carriers of PM, the prevalence of anti-T cruzi antibodies was high: 17% .
In the Hospital Córdoba study, there were no significant differences in positive or negative serology, age or gender, although there was a slight predominance of the male gender both in those with positive serology as in those with negative serology, similar to what was presented by other Argentine publications as those by Arce  and Romero Villanueva . On the contrary, García Rincón in Brazil, reported a predominance of the female gender in chagasic patients . There are many Latin American registries that show a different reality from that of Hospital Córdoba, in regard to age, of the infected individuals when compared to those not infected.
In the same geographical area, in the previous decade, Brunetto published that the average age of infected individuals was 43 years versus 61 years in those serologically negative . The age difference between both samples cannot be explained with the data published, and neither by different types of treatment, as in none of these populations antiparasitic treatment was conducted, except in the cases diagnosed in the acute period of chagasic infection.
The average age in chagasic individuals was lower in other publications in regard to those at Hospital Córdoba, where the serologically negative ones presented higher mean ages in comparison to non-chagasic ones [33,34,36]. There is no information published that would allow comparing and explaining the existing differences in the different regions of South America.
At Hospital Córdoba, in the total sample that was the object of this study, AVB had a greater presence in serologically negative individuals than in positive ones, while the opposite occurred in patients with SND/TBS, in whom there was a greater presence of positive rather than negative serology (Table 5). Tenton  and Nuñez , in Argentina, reported 32.3% and 16.7% respectively, of SND in their serologically positive populations; while Vanegas in Brazil , reported SND in 52% of cases.
There is no fair assessment of the differences reported on the causes leading to the indication of first implant of PM. Could it be a different compromise by Tripanosoma in the different regions? Could the gender differences explain the different compromise by Tripanosoma cruzi on the sinus node and/or AV node? Could there be a higher or lower “sensitivity” or “threshold” of the physicians responsible for the indication of first implant of PM in patients with SND/TBS? The “hard” datum of CAVB is less discussed in the indication of the first implant than the variability that may exist in the clinical and electrocardiographic presentation, when evaluating a patient with possible SND.
In patients who undergo FI of PM at an Argentine public hospital, the average age was 63.8 years, with AVB as the predominant cause. There was 19% of re-sterilized generations that were implanted and no problems during follow-up. There was an evident predominance of single-chamber ventricular pacing (81.6%) in the studied population, mainly motivated by budgetary reasons. The incidence of positive serology for Chagas disease was important, with an average age similar to non-chagasic ones. Serologically positive women showed a higher incidence of SND, and serologically negative men a higher incidence of AVB.
To Silvia Barzón, biochemist and advisor on statistics, Sanatorio Allende, Córdoba.
Braunwald E, Bonow RO, Libby P et al. Braunwald’s Heart Disease. 9th edition. Philadelphia. Elsevier; 2012
Cardiología basada en la evidencia y la experiencia de la Fundación Favaloro, 2 vols. 2da edición. Santiago de Chile. Mediterráneo. 2010.
Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Hert J 2013; 34: 2281-329,
Muratore CA, Baranchuk A. Current and emerging therapeutic options for the treatment of chronic chagasic cardiomyopathy. Vasc Health Risk Manag 2010; 6: 593-601.
Clark EH, Sherbuk J, Okamoto E, et al. Hyperendemic Chagas Disease and the Unmet Need for Pacemakers in the Bolivian Chaco, PLOS Neglected Tropical Diseases. 2014; June https://doi.org/10.1371/journal.pntd.0002801.
Machado FS, Jelicks LA, Kirchhoff LV, et al. Chagas Heart Disease: Report on Recent Developments. Cardiol Rev 2012; 20: 53-65.
Pereira Nunes MC, Dones W, Morillo CA, et al. Chagas Disease: An Overview of Clinical and Epidemiological Aspects. J Am Coll Cardiol 2013; 62: 767-76.
Casola Crespo R, Casola Crespo E, Ramírez Lana LJ, et al. Registro de implante de MP: trece años de experiencia. Rev. Arch Med Camagüey. 2016; 20: 135-44.
Cano Pereza O, Pombo Jimeneza M, Coma Samartına R. Registro español de Marcapasos. XII Informe Oficial de la Sección de Estimulación Cardiaca de la Sociedad Española de Cardiología. Rev Esp Cardiol. 2015; 68: 1138-53.
Proclemer A, Ghidina M, Gregori D, et al. Trend of the main clinical characteristics and pacing modality in patients treated by pacemaker: data from the Italian Pacemaker Registry for the quinquennium 2003–07. Europace 2010; 12: 202-9.
Nowak B, Tasche K, Barnewold L, et al. Association between hospital procedure volume and early complications after pacemaker implantation: results from a large, unselected, contemporary cohort of the German nationwide obligatory external quality assurance programme. Europace 2015; 17: 787-93.
Styliadis IH, Mantziari AP, Gouzoumas NI, et al. Indications for permanent pacing and pacing mode prescription from 1989 to 2006. Experience of a single academic centre in Northern Greece. Hellenic J Cardiol. 2008; 49:155-62.
Tuppina P, Neumanna A, Marijonb E, et al. Implantation and patient profiles for pacemakers and cardioverter-defibrillators in France (2008-2009). Arch Cardiovasc Dis 2011; 104: 332-42.
Greenspon AJ, Patel JD, Lau E, et al. Trends in permanent pacemaker implantation in the United States from 1993 to 2009. Increasing complexity of patients and procedures. J Am Coll Cardiol 2012; 60: 1540-45.
Connolly SJ, Kerr CR, Gent M et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian trial of physiologic pacing investigators. N Engl J Med. 2000; 342:1385–91.
Lamas GA, Lee KL, Sweeney MO et al for the Mode Selection Trial in Sinus-Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002. 346: 1854-62.
Andersen HR, Thuesen L, Bagger JP, et al. Prospective randomized trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet 1994; 344: 1523-28.
Andersen HR, Nielsen JC, Thomsen PE et al. Long-term follow-up of patients from a randomized trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997; 350: 1210-16.
Sweeney MO, Bank AJ, Nsah E, et al. Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med. 2007; 357: 1000-8.
Nielsen JC, Kristensen L, Andersen HR, et al. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol. 2003; 42: 614-23.
Healey JS, Toff WD, Lamas GA, et al. Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation 2006; 114: 11-7.
Fored CM, Granath F, Gadler F, et al. Atrial vs. dual-chamber cardiac pacing in sinus node disease: a register-based cohort study. Europace 2008; 10: 825-31.
Toff WD, Camm AJ, Skehan JD. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med. 2005; 353: 145-55.
Leclercq C, Gras D, Le Helloco A, et al. Hemodynamic importance of preserving the normal sequence of ventricular activation in permanent cardiac pacing. Am Heart J 1995; 129: 1133-41.
Rosenqvist M, Isaaz K, Botvinick EH, et al. Relative importance of activation sequence compared to atrioventricular synchrony in left ventricular function. Am J Cardiol 1991; 67: 148-56.
Hasan R, Ghanbari H, Feldman D, et al. Safety, efficacy, and performance of implanted recycled cardiac rhythm management (CRM) devices in underprivileged patients.. Pacing Clin Electrophysiol 2011; 34: 653-58.
Kantharia BK, Patel SS, Kulkarni G, et al. Reuse of explanted permanent pacemakers donated by funeral homes.. Am J Cardiol 2011; 109: 238-40.
Sandeep Patel, Gaurav Kulkarni, et al. Reuse of Explanted Pacemakers at a Charity Hospital in India. J Am Coll Cardiol 2011; 57 (14); Supplement.e82.
Abuhab A, Trindade E, Aulicino GB, et al. Chagas’ cardiomyopathy: the economic burden of an expensive and neglected disease. Int J Cardiol. 2013; 168: 2375-80.
Castillo-Riquelme M, Guhl F, Turriago B, et al. The costs of preventing and treating Chagas disease in Colombia. PLOS Negl Trop Dis 2008. doi.org/10.1371/journal.pntd.0000336
Brunetto JF. Tratamiento eléctrico de las arritmias en la miocardiopatía chagásica crónica. Rev Fed Arg Cardiol 1980; 10: 164-69.