Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2017

Open Access 01-12-2017 | Research article

Cryoballoon vs. open irrigated radiofrequency ablation for paroxysmal atrial fibrillation: long-term FreezeAF outcomes

Authors: Armin Luik, Kevin Kunzmann, Patrick Hörmann, Kerstin Schmidt, Andrea Radzewitz, Peter Bramlage, Thomas Schenk, Gerhard Schymik, Matthias Merkel, Meinhard Kieser, Claus Schmitt

Published in: BMC Cardiovascular Disorders | Issue 1/2017

Login to get access

Abstract

Background

Effective treatment of paroxysmal atrial fibrillation (AF) is essential for reducing the risk of stroke and heart failure. Cryoballoon (CB) ablation has been developed as an alternative to the use of radiofrequency (RF) energy for electrical isolation of the pulmonary veins. Herein, we provide long-term data regarding the efficacy of CB ablation in comparison to RF.

Methods

FreezeAF was a randomised non-inferiority study comparing CB ablation with RF ablation for the treatment of patients with drug-refractory paroxysmal AF. Procedural success for the long-term follow-up (30 months) was defined as freedom from AF with an absence of persistent complications.

Results

Of the 315 patients that were randomised and received catheter ablation, 292 (92.7%) completed the 30-month follow-up (147 in the RF group and 145 in the CB group). The baseline characteristics of the RF and CB groups were similar. Single-procedure success was achieved by 40% of patients in the RF group and 42% of the CB group (p < 0.001 for non-inferiority). When including re-do procedures in the analysis, the multiple procedure success rate was 72% in the RF group and 76% in the CB group.

Conclusion

The data provide long-term evidence that CB ablation is non-inferior to RF ablation, with high proportions of patients reporting freedom from AF 30 months after the index procedure.

Trial registration

ClinicalTrials.​gov Identifier: NCT00774566; first registered October 16, 2008; first patient included October 20, 2008.
Literature
1.
go back to reference 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(5):359–64.CrossRefPubMed 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(5):359–64.CrossRefPubMed
2.
go back to reference Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham heart study. Circulation. 1998;98(10):946–52.CrossRefPubMed Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham heart study. Circulation. 1998;98(10):946–52.CrossRefPubMed
3.
go back to reference Lafuente-Lafuente C, Longas-Tejero MA, Bergmann JF, Belmin J. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. The Cochrane database of systematic reviews. 2012;5:CD005049. Lafuente-Lafuente C, Longas-Tejero MA, Bergmann JF, Belmin J. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. The Cochrane database of systematic reviews. 2012;5:CD005049.
4.
go back to reference Hakalahti A, Biancari F, Nielsen JC, Raatikainen MJ. Radiofrequency ablation vs. antiarrhythmic drug therapy as first line treatment of symptomatic atrial fibrillation: systematic review and meta-analysis. Europace. 2015;17(3):370–8.CrossRefPubMed Hakalahti A, Biancari F, Nielsen JC, Raatikainen MJ. Radiofrequency ablation vs. antiarrhythmic drug therapy as first line treatment of symptomatic atrial fibrillation: systematic review and meta-analysis. Europace. 2015;17(3):370–8.CrossRefPubMed
5.
go back to reference Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of Atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace. 2012;14(4):528–606.CrossRefPubMed Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of Atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace. 2012;14(4):528–606.CrossRefPubMed
6.
go back to reference Schmidt M, Dorwarth U, Andresen D, Brachmann J, Kuck K, Kuniss M, Willems S, Deneke T, Tebbenjohanns J, Gerds-Li JH, et al. German ablation registry: Cryoballoon vs radiofrequency ablation in paroxysmal atrial fibrillation-one-year outcome data. Heart Rhythm. 2016;13(4):836–44.CrossRefPubMed Schmidt M, Dorwarth U, Andresen D, Brachmann J, Kuck K, Kuniss M, Willems S, Deneke T, Tebbenjohanns J, Gerds-Li JH, et al. German ablation registry: Cryoballoon vs radiofrequency ablation in paroxysmal atrial fibrillation-one-year outcome data. Heart Rhythm. 2016;13(4):836–44.CrossRefPubMed
7.
go back to reference Andrade JG, Khairy P, Guerra PG, Deyell MW, Rivard L, Macle L, Thibault B, Talajic M, Roy D, Dubuc M. Efficacy and safety of cryoballoon ablation for atrial fibrillation: a systematic review of published studies. Heart Rhythm. 2011;8(9):1444–51.CrossRefPubMed Andrade JG, Khairy P, Guerra PG, Deyell MW, Rivard L, Macle L, Thibault B, Talajic M, Roy D, Dubuc M. Efficacy and safety of cryoballoon ablation for atrial fibrillation: a systematic review of published studies. Heart Rhythm. 2011;8(9):1444–51.CrossRefPubMed
8.
go back to reference Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, et al. Cryoballoon or radiofrequency ablation for paroxysmal Atrial fibrillation. N Engl J Med. 2016;374(23):2235–45.CrossRefPubMed Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, et al. Cryoballoon or radiofrequency ablation for paroxysmal Atrial fibrillation. N Engl J Med. 2016;374(23):2235–45.CrossRefPubMed
9.
go back to reference Metzner A, Heeger CH, Wohlmuth P, Reissmann B, Rillig A, Tilz RR, Mathew S, Lemes C, Deiss S, Maurer T, et al. Two-year outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon: lessons from the bonus freeze protocol. Clin Res Cardiol. 2016;105(1):72–8.CrossRefPubMed Metzner A, Heeger CH, Wohlmuth P, Reissmann B, Rillig A, Tilz RR, Mathew S, Lemes C, Deiss S, Maurer T, et al. Two-year outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon: lessons from the bonus freeze protocol. Clin Res Cardiol. 2016;105(1):72–8.CrossRefPubMed
10.
go back to reference Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the north American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013;61(16):1713–23.CrossRefPubMed Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the north American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013;61(16):1713–23.CrossRefPubMed
11.
go back to reference Malmborg H, Lonnerholm S, Blomstrom P, Blomstrom-Lundqvist C: Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter: a randomized controlled study comparing the clinical outcome and safety; the AF-COR study. Europace. 2013, 15(11):1567-1573. Malmborg H, Lonnerholm S, Blomstrom P, Blomstrom-Lundqvist C: Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter: a randomized controlled study comparing the clinical outcome and safety; the AF-COR study. Europace. 2013, 15(11):1567-1573.
12.
go back to reference Mugnai G, Chierchia GB, de Asmundis C, Sieira-Moret J, Conte G, Capulzini L, Wauters K, Rodriguez-Manero M, Di Giovanni G, Baltogiannis G, et al. Comparison of pulmonary vein isolation using cryoballoon versus conventional radiofrequency for paroxysmal atrial fibrillation. Am J Cardiol. 2014;113(9):1509–13.CrossRefPubMed Mugnai G, Chierchia GB, de Asmundis C, Sieira-Moret J, Conte G, Capulzini L, Wauters K, Rodriguez-Manero M, Di Giovanni G, Baltogiannis G, et al. Comparison of pulmonary vein isolation using cryoballoon versus conventional radiofrequency for paroxysmal atrial fibrillation. Am J Cardiol. 2014;113(9):1509–13.CrossRefPubMed
13.
go back to reference Squara F, Zhao A, Marijon E, Latcu DG, Providencia R, Di Giovanni G, Jauvert G, Jourda F, Chierchia GB, De Asmundis C, et al. Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation. Europace. 2015;17(5):718–24.CrossRefPubMed Squara F, Zhao A, Marijon E, Latcu DG, Providencia R, Di Giovanni G, Jauvert G, Jourda F, Chierchia GB, De Asmundis C, et al. Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation. Europace. 2015;17(5):718–24.CrossRefPubMed
14.
go back to reference Wasserlauf J, Pelchovitz DJ, Rhyner J, Verma N, Bohn M, Li Z, Arora R, Chicos AB, Goldberger JJ, Kim SS et al: Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation. Pacing and clinical electrophysiology : PACE 2015. Wasserlauf J, Pelchovitz DJ, Rhyner J, Verma N, Bohn M, Li Z, Arora R, Chicos AB, Goldberger JJ, Kim SS et al: Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation. Pacing and clinical electrophysiology : PACE 2015.
15.
go back to reference Jourda F, Providencia R, Marijon E, Bouzeman A, Hireche H, Khoueiry Z, Cardin C, Combes N, Combes S, Boveda S, et al. Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation. Europace. 2015;17(2):225–31.CrossRefPubMed Jourda F, Providencia R, Marijon E, Bouzeman A, Hireche H, Khoueiry Z, Cardin C, Combes N, Combes S, Boveda S, et al. Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation. Europace. 2015;17(2):225–31.CrossRefPubMed
16.
go back to reference Luik A, Radzewitz A, Kieser M, Walter M, Bramlage P, Hormann P, Schmidt K, Horn N, Brinkmeier-Theofanopoulou M, Kunzmann K, et al. Cryoballoon versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation: the prospective, randomized, controlled, noninferiority FreezeAF study. Circulation. 2015;132(14):1311–9.CrossRefPubMedPubMedCentral Luik A, Radzewitz A, Kieser M, Walter M, Bramlage P, Hormann P, Schmidt K, Horn N, Brinkmeier-Theofanopoulou M, Kunzmann K, et al. Cryoballoon versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation: the prospective, randomized, controlled, noninferiority FreezeAF study. Circulation. 2015;132(14):1311–9.CrossRefPubMedPubMedCentral
17.
go back to reference Kuck KH, Furnkranz A, Chun KR, Metzner A, Ouyang F, Schluter M, Elvan A, Lim HW, Kueffer FJ, Arentz T, et al. Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial. Eur Heart J. 2016;37(38):2858–65.CrossRefPubMedPubMedCentral Kuck KH, Furnkranz A, Chun KR, Metzner A, Ouyang F, Schluter M, Elvan A, Lim HW, Kueffer FJ, Arentz T, et al. Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial. Eur Heart J. 2016;37(38):2858–65.CrossRefPubMedPubMedCentral
18.
go back to reference Hunter RJ, Baker V, Finlay MC, Duncan ER, Lovell MJ, Tayebjee MH, Ullah W, Siddiqui MS, Mc LA, Richmond L, et al. Point-by-point radiofrequency ablation versus the cryoballoon or a novel combined approach: a randomized trial comparing 3 methods of pulmonary vein isolation for paroxysmal atrial fibrillation (the Cryo versus RF trial). J Cardiovasc Electrophysiol. 2015;26(12):1307–14.CrossRefPubMed Hunter RJ, Baker V, Finlay MC, Duncan ER, Lovell MJ, Tayebjee MH, Ullah W, Siddiqui MS, Mc LA, Richmond L, et al. Point-by-point radiofrequency ablation versus the cryoballoon or a novel combined approach: a randomized trial comparing 3 methods of pulmonary vein isolation for paroxysmal atrial fibrillation (the Cryo versus RF trial). J Cardiovasc Electrophysiol. 2015;26(12):1307–14.CrossRefPubMed
19.
go back to reference Luik A, Merkel M, Hoeren D, Riexinger T, Kieser M, Schmitt C. Rationale and design of the FreezeAF trial: a randomized controlled noninferiority trial comparing isolation of the pulmonary veins with the cryoballoon catheter versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation. Am Heart J. 2010;159(4):555–60. e551CrossRefPubMed Luik A, Merkel M, Hoeren D, Riexinger T, Kieser M, Schmitt C. Rationale and design of the FreezeAF trial: a randomized controlled noninferiority trial comparing isolation of the pulmonary veins with the cryoballoon catheter versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation. Am Heart J. 2010;159(4):555–60. e551CrossRefPubMed
20.
go back to reference Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med. 1990;9(12):1447–54.CrossRefPubMed Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med. 1990;9(12):1447–54.CrossRefPubMed
21.
go back to reference Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med. 2002;21(16):2409–19.CrossRefPubMed Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med. 2002;21(16):2409–19.CrossRefPubMed
22.
go back to reference Van Buuren S. Groothuis-Oudshoorn K: mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1–67. Van Buuren S. Groothuis-Oudshoorn K: mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1–67.
23.
go back to reference Conti S, Moltrasio M, Fassini G, Tundo F, Riva S, Dello Russo A, Casella M, Majocchi B, Marino V, De Iuliis P, et al. Comparison between first- and second-generation cryoballoon for paroxysmal atrial fibrillation ablation. Cardiol Res Pract. 2016;2016:5106127.PubMedPubMedCentral Conti S, Moltrasio M, Fassini G, Tundo F, Riva S, Dello Russo A, Casella M, Majocchi B, Marino V, De Iuliis P, et al. Comparison between first- and second-generation cryoballoon for paroxysmal atrial fibrillation ablation. Cardiol Res Pract. 2016;2016:5106127.PubMedPubMedCentral
24.
go back to reference Furnkranz A, Bordignon S, Dugo D, Perotta L, Gunawardene M, Schulte-Hahn B, Nowak B, Schmidt B, Chun JK. Improved 1-year clinical success rate of pulmonary vein isolation with the second-generation cryoballoon in patients with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 2014;25(8):840–4.CrossRefPubMed Furnkranz A, Bordignon S, Dugo D, Perotta L, Gunawardene M, Schulte-Hahn B, Nowak B, Schmidt B, Chun JK. Improved 1-year clinical success rate of pulmonary vein isolation with the second-generation cryoballoon in patients with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 2014;25(8):840–4.CrossRefPubMed
25.
go back to reference Knecht S, Sticherling C, von Felten S, Conen D, Schaer B, Ammann P, Altmann D, Osswald S, Kuhne M. Long-term comparison of cryoballoon and radiofrequency ablation of paroxysmal atrial fibrillation: a propensity score matched analysis. Int J Cardiol. 2014;176(3):645–50.CrossRefPubMed Knecht S, Sticherling C, von Felten S, Conen D, Schaer B, Ammann P, Altmann D, Osswald S, Kuhne M. Long-term comparison of cryoballoon and radiofrequency ablation of paroxysmal atrial fibrillation: a propensity score matched analysis. Int J Cardiol. 2014;176(3):645–50.CrossRefPubMed
26.
go back to reference Neumann T, Wojcik M, Berkowitsch A, Erkapic D, Zaltsberg S, Greiss H, Pajitnev D, Lehinant S, Schmitt J, Hamm CW, et al. Cryoballoon ablation of paroxysmal atrial fibrillation: 5-year outcome after single procedure and predictors of success. Europace. 2013;15(8):1143–9.CrossRefPubMed Neumann T, Wojcik M, Berkowitsch A, Erkapic D, Zaltsberg S, Greiss H, Pajitnev D, Lehinant S, Schmitt J, Hamm CW, et al. Cryoballoon ablation of paroxysmal atrial fibrillation: 5-year outcome after single procedure and predictors of success. Europace. 2013;15(8):1143–9.CrossRefPubMed
27.
go back to reference Casado-Arroyo R, Chierchia GB, Conte G, Levinstein M, Sieira J, Rodriguez-Manero M, di Giovanni G, Baltogiannis Y, Wauters K, de Asmundis C, et al. Phrenic nerve paralysis during cryoballoon ablation for atrial fibrillation: a comparison between the first- and second-generation balloon. Heart Rhythm. 2013;10(9):1318–24.CrossRefPubMed Casado-Arroyo R, Chierchia GB, Conte G, Levinstein M, Sieira J, Rodriguez-Manero M, di Giovanni G, Baltogiannis Y, Wauters K, de Asmundis C, et al. Phrenic nerve paralysis during cryoballoon ablation for atrial fibrillation: a comparison between the first- and second-generation balloon. Heart Rhythm. 2013;10(9):1318–24.CrossRefPubMed
28.
go back to reference Nakamura K, Naito S, Sasaki T, Nakano M, Minami K, Nakatani Y, Ikeda K, Yamashita E, Kumagai K, Funabashi N, et al. Randomized comparison of contact force-guided versus conventional circumferential pulmonary vein isolation of atrial fibrillation: prevalence, characteristics, and predictors of electrical reconnections and clinical outcomes. J Interv Card Electrophysiol. 2015;44(3):235–45.CrossRefPubMed Nakamura K, Naito S, Sasaki T, Nakano M, Minami K, Nakatani Y, Ikeda K, Yamashita E, Kumagai K, Funabashi N, et al. Randomized comparison of contact force-guided versus conventional circumferential pulmonary vein isolation of atrial fibrillation: prevalence, characteristics, and predictors of electrical reconnections and clinical outcomes. J Interv Card Electrophysiol. 2015;44(3):235–45.CrossRefPubMed
29.
go back to reference Wakili R, Clauss S, Schmidt V, Ulbrich M, Hahnefeld A, Schussler F, Siebermair J, Kaab S, Estner HL. Impact of real-time contact force and impedance measurement in pulmonary vein isolation procedures for treatment of atrial fibrillation. Clin Res Cardiol. 2014;103(2):97–106.CrossRefPubMed Wakili R, Clauss S, Schmidt V, Ulbrich M, Hahnefeld A, Schussler F, Siebermair J, Kaab S, Estner HL. Impact of real-time contact force and impedance measurement in pulmonary vein isolation procedures for treatment of atrial fibrillation. Clin Res Cardiol. 2014;103(2):97–106.CrossRefPubMed
30.
go back to reference Aryana A, Singh SM, Kowalski M, Pujara DK, Cohen AI, Singh SK, Aleong RG, Banker RS, Fuenzalida CE, Prager NA, et al. Acute and long-term outcomes of catheter ablation of atrial fibrillation using the second-generation cryoballoon versus open-irrigated radiofrequency: a multicenter experience. J Cardiovasc Electrophysiol. 2015;26(8):832–9.CrossRefPubMed Aryana A, Singh SM, Kowalski M, Pujara DK, Cohen AI, Singh SK, Aleong RG, Banker RS, Fuenzalida CE, Prager NA, et al. Acute and long-term outcomes of catheter ablation of atrial fibrillation using the second-generation cryoballoon versus open-irrigated radiofrequency: a multicenter experience. J Cardiovasc Electrophysiol. 2015;26(8):832–9.CrossRefPubMed
31.
go back to reference Khoueiry Z, Albenque JP, Providencia R, Combes S, Combes N, Jourda F, Sousa PA, Cardin C, Pasquie JL, Cung TT, et al. Outcomes after cryoablation vs. radiofrequency in patients with paroxysmal atrial fibrillation: impact of pulmonary veins anatomy. Europace. 2016;18(9):1343–51.CrossRefPubMed Khoueiry Z, Albenque JP, Providencia R, Combes S, Combes N, Jourda F, Sousa PA, Cardin C, Pasquie JL, Cung TT, et al. Outcomes after cryoablation vs. radiofrequency in patients with paroxysmal atrial fibrillation: impact of pulmonary veins anatomy. Europace. 2016;18(9):1343–51.CrossRefPubMed
32.
go back to reference Kuck K, Brugada J, Albenque J. Cryoballoon or radiofrequency ablation for Atrial fibrillation. N Engl J Med. 2016;375(11):1100–1.PubMed Kuck K, Brugada J, Albenque J. Cryoballoon or radiofrequency ablation for Atrial fibrillation. N Engl J Med. 2016;375(11):1100–1.PubMed
33.
go back to reference Friede T, Mitchell C, Muller-Velten G. Blinded sample size reestimation in non-inferiority trials with binary endpoints. Biom JBiochem Z. 2007;49(6):903–16. Friede T, Mitchell C, Muller-Velten G. Blinded sample size reestimation in non-inferiority trials with binary endpoints. Biom JBiochem Z. 2007;49(6):903–16.
Metadata
Title
Cryoballoon vs. open irrigated radiofrequency ablation for paroxysmal atrial fibrillation: long-term FreezeAF outcomes
Authors
Armin Luik
Kevin Kunzmann
Patrick Hörmann
Kerstin Schmidt
Andrea Radzewitz
Peter Bramlage
Thomas Schenk
Gerhard Schymik
Matthias Merkel
Meinhard Kieser
Claus Schmitt
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2017
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-017-0566-6

Other articles of this Issue 1/2017

BMC Cardiovascular Disorders 1/2017 Go to the issue