CLINICAL RESEARCH
Europace (2014) 16, 1175–1180 doi:10.1093/europace/euu015
Sudden death and ICDs
Sex differences in implantable cardioverterdefibrillator implantation indications and outcomes: lessons from the Nationwide Israeli-ICD Registry Guy Amit 1,2*, Mahmoud Suleiman 3, Yuval Konstantino 1, David Luria 1,4, Mark Kazatsker 5, Israel Chetboun 6, Moti Haim 6, Natalie Gavrielov-Yusim 7, Ilan Goldenberg 7, and Michael Glikson 1,4 On behalf of the Israeli Working Group on Pacing and Electrophysiology 1 Cardiology Department, Soroka Medical Center, Beer-Sheva, Israel; 2Division of Cardiology, Department of Medicine McMaster University, Hamilton General Hospital 237 Barton Street East, Hamilton, ON L8L 2X2, Canada; 3Cardiology Department, Rambam Medical Center, Haifa, Israel; 4Cardiology Department, Sheba Medical Center, Tel Hashomer, Israel; 5 Cardiology Department, Hillel Yafe Hospital, Hadera, Israel; 6Cardiology Department, Meir Hospital, Kfar Saba, Israel; and 7IACT-Neufeld Cardiac Research Institute, Tel Hashomer, Israel
Aims
Implantable cardioverter-defibrillators (ICDs) improve survival in certain high arrhythmic risk populations. However, there are sex differences regarding both the utilization and the benefit of these devices. Using a prospective national ICD registry, we aim to compare the indications for ICD implantation as well as outcomes in implanted women vs. men. ..................................................................................................................................................................................... Methods All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July and results 2010 and February 2013 were included. A total of 3544 subjects constructed the baseline cohort, of whom 615 (17%) were women. Women had the same age (64 years) and rate of secondary prevention indication (26%) as men. However, women were more likely than men to have significant heart failure symptoms (52 vs. 45%), QRS . 120 ms (41 vs. 36%), and a higher rate of non-ischaemic cardiomyopathy (54 vs. 21%, all P values ,0.05). Using multivariate analysis, women were more likely to undergo CRTD implantation (odds ratio ¼ 1.8, P , 0.01). Follow-up data were available for 1518 subjects with a mean follow-up of 12 months. During follow-up, there were no significant differences among genders in the rate of any single or the combined outcomes of appropriate device therapies, heart failure admissions, or death. First-year re-intervention rate was double among women (5.6 vs. 3.0%, P , 0.01). ..................................................................................................................................................................................... Conclusion In real-world setting, women implanted with an ICD differ significantly from men in their baseline characteristics and in the use of CRTD devices. These, however, did not translate into outcome differences.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Implantable cardioverter-defibrillators † Cardiac resynchronization therapy † Women † Outcomes † Registry
Background Numerous studies have consistently shown that implantable cardioverter-defibrillators (ICDs) reduce mortality when used for the primary prevention of sudden cardiac death1 – 3 or for the secondary prevention of such an event.4,5 Accordingly, current practice guidelines6,7 advocate implantation of ICDs according to the characteristics of the populations studied; including those with
previous myocardial infarction (MI) or heart failure (HF) with significantly reduced left ventricular ejection fraction (LVEF) of ,0.30– 0.35, and those who survived life-threatening ventricular arrhythmia such as ventricular tachycardia or fibrillation. Although current guidelines apply to both women and men, there are sex-related differences in the rate of utilization of ICDs. Recent studies suggested that men were three times more likely to receive a device for primary prevention and more than twice for secondary
* Corresponding author. Cardiology Department, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University, POB 151, Beer-Sheva, Israel. Tel: +1 905-527-4322; fax: +1 905-577-1447, E-mail: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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Received 26 July 2013; accepted after revision 16 January 2014; online publish-ahead-of-print 19 February 2014
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What’s new? † Women implanted with an implantable cardioverterdefibrillator (ICD) have a higher rate than men of advanced heart failure symptoms. † Women are implanted more often than men with a resynchronization device. † Among the secondary prevention groups, women present more often with ventricular fibrillation rather than ventricular tachycardia. † Women have a higher re-intervention rate than men. † Women implanted with an ICD have same the same shortterm rate of device therapies, heart failure admissions, and death as men.
Methods Study population All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July 2010 and February 2013 were included. The registry was approved by the ethics committee of each participating institution and the patients provided written informed consent. Data were prospectively collected from the index hospitalization at the time of initial ICD implantation or device upgrade by the local electrophysiologist at the implanting centre and entered into a secure, firewall, and password protected web-based electronic case report form. Data collected included demographic, clinical, and procedure-related variables.
Follow-up Follow-up was requested from all centres at a median time of 1 year post-implantation. Mean compliance rate with the follow-up queries was about 50%. Data collected included: the occurrence of death, re-hospitalization for HF or other cardiovascular cause, re-hospitalization for device-related events, and the number and appropriateness of therapies (shock or anti tachycardia pacing) for ventricular tachyarrhythmias.
Statistical analyses Baseline variables were compared using Student’s t-test, analysis of variance, or x2 as appropriate. Logistic regression was used to predict CRTD implantation using gender, New York Heart Association (NYHA) HF class, LVEF, QRS width, implantation indication, and renal function as prespecified covariates. Cox regression was used to assess for independent predictors of mortality, and of appropriate ICD therapy or mortality
during follow-up. Best-fitted stepwise models were built according to the P values of all baseline parameters.
Results Patient population A total of 3544 subjects were included in the baseline cohort, of whom 615 (17%) were women. The mean age was 64 in both the groups. There were significant differences between genders at baseline: coronary artery disease was less prevalent (46 vs. 79%, P , 0.01) and dilated cardiomyopathy was more prevalent (38 vs. 18%, P , 0.01) among women. Likewise, risk factors for coronary disease, including diabetes, hypertension, smoking, and dyslipidaemia were less frequent among women (Table 1). Implanted women had a higher rate of advanced HF, a wider QRS, and a higher proportion of left bundle branch block (LBBB). Women had a lower haemoglobin level and a lower glomerular filtration rate at implantation. Women were treated less frequently with betablockers. The rate of secondary prevention indication for ICD implantation was similar between women and men. However, among the secondary prevention group, documented ventricular fibrillation (VF) was more common (43 vs. 32%), and sustained ventricular tachycardia (VT) was less common (36 vs. 44%) among women (P ¼ 0.01).
Device type Overall, 40% received dual-chamber ICD, 20% received singlechamber ICD, and 40% received CRTD. Women were more likely to undergo CRTD implantation (46 vs. 37%, P , 0.001). Using multivariate analysis, women were almost twice as likely to receive a CRTD device at implantation [odds ratio ¼ 1.8, 95% confidence interval (CI): 1.2 –2.7]. In both women and men, a more advanced NYHA class, a wide QRS, a lower LVEF, primary prevention indication, and age were all independently associated with implantation of a CRTD device; whereas in men, more advanced renal disease was an additional predictor.
Risk of appropriate implantable cardioverter-defibrillator therapy, heart failure hospitalization, or death The follow-up cohort included 1518 patients, of whom 252 (17%) were women. There were no significant baseline differences between the patients with and without follow-up data available. Median follow-up time was 323 days, and the first outcome event was appropriate ICD therapy in 81 subjects (6.1%), HF exacerbation needing admission in 100 subjects (8.1%), and death in 77 subjects (5.4%). Kaplan–Meier survival analysis showed no significant difference between men and women in the cumulative probability for appropriate ICD therapy or death in the whole study cohort, as well as in the primary prevention and the secondary prevention groups (Figure 1A and B, respectively). Similarly, the cumulative probability of HF admission or death during follow-up was not significantly different between men and women receiving both the ICD and the CRTD devices (Figure 2A and B, respectively). Consistent with the univariate findings, multivariate analysis showed that gender was not independently
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prevention,8 and although the rate of ICD utilization among women steadily increased over the years, it is still significantly lower than in men.9 Furthermore, a meta-analysis found no survival benefit for ICDs in women with HF and primary prevention indication.10 Thus, there is an urgent need to further elucidate the benefits and harms of ICDs among women. The Israeli ICD registry is a prospective nationwide database of all ICD implants. Herein, we aim at comparing the indication for ICD implantation as well as the outcome in women vs. men in a reallife scenario.
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Sex differences in ICD implantation indications and outcomes
Table 1 Comorbidities, baseline, and device characteristics according to gender N (%)
Women N 5 615
Men N 5 2927
P value
............................................................................................................................................................................... Age mean + SD
64 + 14
64 + 13
0.19
Diabetes
192 (31)
1075 (37)
,0.01
Hypertension Dyslipidaemia
346 (57) 288 (47)
1864 (64) 1618 (56)
,0.01 ,0.01
74 (12)
1014 (35)
,0.01
Atrial fibrillation Ischaemic cardiomyopathy
123 (20) 282 (46)
620 (21) 2305 (79)
0.49 ,0.01
Dilated cardiomyopathy
234 (38)
529 (18)
,0.01
62 (11)
166 (6)
Smoking
Left ventricular ejection fraction Normal (≥50%) Mild dysfunction (40–49%)
,0.01 30 (5)
161 (6)
161 (28) 320 (56)
937 (34) 1525 (54)
I II
36 (8) 192 (40)
233 (10) 1037 (45)
III
242 (51)
1022 (44)
Moderate dysfunction (30– 39%) Severe dysfunction (,30%) HF; NYHA class
0.02
8 (1) 120 + 32
27 (1) 118 + 30
0.05
QRS ≥ 120 ms:
251 (41%):
1059 (36%):
0.03
LBBB morphology Haemoglobin level (g/dL) at implantation, median
209 (83%) 12.4
798 (75%) 13.2
0.04 ,0.01
Glomerular filtration rate (mL/min), median Medications ACEI/ARB
67
71
,0.01
435 (71)
2156 (75)
0.08
Beta-blockers
472 (77)
2380 (82)
,0.01
Diuretics Antiarrhythmics
436 (71) 99 (16)
2040 (70) 514 (18)
0.69 0.35
79 (20)
397 (22)
0.42 0.82
Coumadin ICD implantation indication Secondary prevention of sudden death
160 (26):
749 (26):
Resuscitated VF
69 (43)
241 (32)
Spontaneous sustained VT Syncope/unknown aetiology
58 (36) 26 (23)
332 (44) 137 (24)
0.01 ,0.01
Device type Single chamber Dual chamber
117 (19) 218 (35)
623 (21) 1215 (42)
Cardiac resynchronization
280 (46)
1089 (37)
NYHA, New York Heart Association; ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker.
associated with increased risk of all-cause mortality, HF admissions, appropriate ICD therapy, mortality, or combinations of the above, after further adjustment for age, device-type, LVEF, implantation indication, diabetes, use of beta-blockers, and renal function (Table 2).
replacement) and 5 system removals. The re-intervention rate was significantly higher among women vs. men (5.6 vs. 3.0%, P ¼ 0.02). These rates were 4.4 vs. 2.6% (P ¼ 0.24), and 6.9 vs. 3.7% (P ¼ 0.13), among the ICD and the CRTD groups, respectively.
Re-intervention rate
Discussion
There were 52 re-interventions during the first year in the follow-up cohort (3.4%) including 45 lead-related procedures (reposition/
Using a nationwide comprehensive ICD registry, we found the following major findings: there are significant differences in the clinical
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IV QRS duration (ms) + SD
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G. Amit et al.
P (log rank) = 0.65
A
P (log rank) = 0.39
B
90
90 Survival (%)
100
Survival (%)
100
80 70 60
80 70 60
Male Female
50
Male Female
50 0
50 100 150 200 250 300 350 400 450 500 Time (days)
0
50 100 150 200 250 300 350 400 450 500 Time (days)
Figure 1 Time to appropriate ICD therapy or death by gender among primary (A) and secondary (B) prevention subjects.
P (log rank) = 0.84
A
P (log rank) = 0.64
B
90
90
80 70 60
80 70 60
Male Female
50
Male Female
50 0
50 100 150 200 250 300 350 400 450 500 Time (days)
0
50 100 150 200 250 300 350 400 450 500 Time (days)
Figure 2 Time to HF admission or death by gender in ICD (A) and CRTD (B) recipients.
Table 2 The impact of gender on different outcomes HR
95% CI
P value
0.83 1.17
0.44– 1.81 0.54– 2.54
0.64 0.69
................................................................................ Death Appropriate therapy HF admission
0.81
0.41– 1.60
0.55
Death or appropriate therapy Death or HF admission
1.03 0.85
0.60– 1.77 0.51– 1.41
0.92 0.53
Data shown are hazard ratios (HRs) in women vs. men adjusted for age, LVEF, CRT, implantation indication, diabetes, use of beta-blockers, and renal function.
characteristics between men and women who receive a device in a real-world setting; women have a higher proportion of nonischaemic cardiomyopathy, and are more likely to be implanted with a CRTD device. Among women implanted for secondary prevention of sudden death, the presenting arrhythmia is more often VF than sustained VT. However, those baseline and
device-type-related differences did not translate into significant gender-related differences in the risk of all-cause mortality, appropriate ICD therapy, or HF admission rates, during follow-up. On the other hand women had a significantly higher re-intervention rate than men. The relatively lower rate of coronary artery disease among implanted women, partially explains the lower participation rate of women in some of the primary prevention studies. Thus, in trials of post-MI patients such as the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II)2 women comprised only 15% of the population studied. This contrasts with the HF studies; in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT),3 where about half of the subjects had non-ischaemic cardiomyopathy, women comprised 24% of the population. Likewise, in the Ontario database,11 where 21% of ICD implants were in women, men had a significantly higher rate of atherosclerosis risk factors and past coronary artery interventions. Furthermore, not only the aetiology of the cardiac disease is different among genders, implanted women have a higher rate of advanced HF, bundle branch blocks, and longer QRS, and therefore are implanted more often with CRTD devices.
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Survival (%)
100
Survival (%)
100
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Sex differences in ICD implantation indications and outcomes
Study limitations include the inherent limitations of a registry, mainly quality and completeness of the data. Although several quality assurance algorithms were applied in the patient registration phase, some devices were probably missed from the national registry. In addition, follow-up information regarding therapies given by the device and readmission rates were reported by the implanting facility following queries sent to 1 year after implantation. It was the implanting physician responsibility to see the patient/medical chart, interrogate the device, and answer the query in a timely manner. If not answered, the queries were re-sent. However, even after adding a phone and an e-mail-based notification system, the response rates varied significantly between the implanting hospitals, and averaged 50%. However, to see whether the response rate introduces a bias regarding our follow-up results (e.g. overemphasizing sicker population with more physician follow-ups), we analysed the baseline characteristics of patients with and without follow-up data were available. No statistical differences were found regarding the basic demographics, co-morbidities, or implant types between the two groups. Therefore, we believe our follow-up data results are valid. In conclusion, in real-world setting, women implanted with an ICD differ significantly from men in baseline characteristics and in the use of CRTD devices. These, however, did not translate to outcome differences. Conflict of interest: none declared.
Funding This work was supported by an unrestricted research grant from Boston Scientific to the Israeli Working Group on Electrophysiology and the Israeli Association for Cardiovascular Trials.
References 1. Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H et al. Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933 –40. 2. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877 –83. 3. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225–37. 4. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337: 1576 –83. 5. Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS et al. Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297 –302. 6. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA III, Freedman RA, Gettes LS et al. ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/ AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51: e1 –62. 7. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M et al. ACC/ AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace 2006;8:746 –837.
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Since the rate of non-ischaemic cardiomyopathy is higher in women than men, and since current primary prevention guidelines advocate that ICD implantation in this population will be based upon HF symptoms, it is not surprising that in real life, women with ICDs are found to have an overall higher rate of HF symptoms, and thus a higher rate of CRTD implantations. There were no significant gender differences in the distribution of primary vs. secondary implantation indication. However, among the secondary prevention subset, women were more often diagnosed with VF than monomorphic VT, probably reflecting the different myocardial pathologies. That is, the baseline differences found in the aetiology of the cardiac disease that led to ICD implantation (i.e. ischaemic vs. non-ischaemic cardiomyopathy) also point to a different arrhythmogenic substrate (monomorphic VT being more prevalent than VF among the post-MI-ischaemic cardiomyopathy patients).12 Even so, at follow-up, we did not observe a significant gender difference in the rate of appropriate therapies or death. These finding contrasts with previous reports which found 31% less appropriate shocks in women over 1 year9 or an analogous two- to three-fold increased hazard for such events in men.8 Both studies did not find a mortality difference between men and women, although one meta-analysis found no ICD survival benefit in women.10 Our lack of association between gender and ICD therapies/death can be attributed to the contemporary programming of the devices, in which slow and non-sustained tachycardias are not treated and therefore the overall rate of treated monomorphic VT events is lower than in previous studies. In addition, no gender differences were found relating to HF admissions both in the ICD and the CRTD group. In contrast to the previous small-scale studies, the MADIT-CRT trial demonstrated significant mortality and HF admissions reduction in women vs. men with CRTD devices, which was attributed to a higher incidence of LBBB and non-ischaemic cardiomyopathy among women.13 Furthermore, the investigators also found, that a greater sex-related difference in responses to CRT was evident in the subgroup of patients with non-ischaemic cardiomyopathy.14 However, in the SMART-AV study, women had a better response to CRT even after adjustment for baseline variables such as ischaemic vs. nonischaemic cardiomyopathy and LBBB.15 According to our data, and given their worse baseline CHF status, women were expected to have higher mortality and HF rates over follow-up. The higher rate of CRT use can partially explain the equal rates of events between genders. Other explanations can be the more benign course of nonischaemic cardiomyopathy, and the relatively short follow-up time. Re-intervention rate was double in women in our registry, where the most common procedure was lead repositioning or replacement. The same pattern was detected in both CRTD and non-CRTD implants, implying that the difference was not due to the higher CRTD rate among women. In the Ontario registry,11 an increase rate of complications were observed in women, an observation reported also in the American national cardiovascular data registry.16 One explanation could be the higher rate of CRTD use among the registry women: using more leads and especially coronary sinus leads predisposes the patient to more lead complications. We can also speculate that some lead designs might be more suitable for men than for women due to intrinsic properties (e.g. weight, screw length, etc.).
1180 8. Curtis LH, Al-Khatib SM, Shea AM, Hammill BG, Hernandez AF, Schulman KA. Sex differences in the use of implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death. JAMA 2007;298:1517 –24. 9. MacFadden DR, Tu JV, Chong A, Austin PC, Lee DS. Evaluating sex differences in population-based utilization of implantable cardioverter-defibrillators: role of cardiac conditions and noncardiac comorbidities. Heart Rhythm 2009;6:1289 –96. 10. Ghanbari H, Dalloul G, Hasan R, Daccarett M, Saba S, David S et al. Effectiveness of implantable cardioverter defibrillators for the primary prevention of sudden cardiac death in women with advanced heart failure: a meta-analysis of randomized controlled trials. Arch Intern Med 2009;169:1500 –6. 11. MacFadden DR, Crystal E, Krahn AD, Mangat I, Healey JS, Dorian P et al. Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database. Ann Intern Med 2012;156:195 –203. 12. Attin M, Ideker RE, Pogwizd SM. Mechanistic insights into ventricular arrhythmias from mapping studies in humans. Heart Rhythm 2008;5(suppl):S53– 8.
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13. Arshad A, Moss AJ, Foster E, Padeletti L, Barsheshet A, Goldenberg I et al. MADIT-CRT Executive Committee. Cardiac resynchronization therapy is more effective in women than in men: the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) trial. J Am Coll Cardiol 2011;57:813 –20. 14. Barsheshet A, Brenyo A, Goldenberg I, Moss AJ. Sex-related differences in patients’ responses to heart failure therapy. Nat Rev Cardiol 2012;9:234 –42. 15. Cheng A, Gold MR, Waggoner AD, Meyer TE, Seth M, Rapkin J et al. Potential mechanisms underlying the effect of gender on response to cardiac resynchronization therapy: insights from the SMART-AV multicenter trial. Heart Rhythm 2012;9: 736 –41. 16. Peterson PN, Daugherty SL, Wang Y, Vidaillet HJ, Heidenreich PA, Curtis JP et al. National Cardiovascular Data Registry. Gender differences in procedure-related adverse events in patients receiving implantable cardioverter-defibrillator therapy. Circulation 2009;119:1078 –84.
EP CASE EXPRESS
doi:10.1093/europace/euu060 Online publish-ahead-of-print 27 March 2014
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Simultaneous re-isolation of the left pulmonary veins and termination of peri-mitral flutter with only an ethanol infusion in the vein of Marshall: killing two birds with one stone Kazuyasu Yoshitani1*, Kazuto Kujira1, and Kaoru Okishige2
* Corresponding author. Tel: +81 6 6482 1521; fax: +81 6 6482 7430. E-mail: [email protected]
A 65-year-old male patient was admitted for ablation of a recurrent atrial A B C tachycardia (AT) after a previous ablation of persistent atrial fibrillation that consisted of a bilateral pulmonary vein (PV) isolation, electrogram-based ablation, and linear ablation at the mitral isthmus (MI) and cavotricuspid isthmus. During the index procedure, bidirectional block of the MI could D not be achieved in spite of a meticulous endocardial radiofrequency ablation as well as from inside the coronary sinus. In the second procedure, a recurrent perimitral AT and reconnection of the left PVs were confirmed. Then a vein of Marshall (VOM) ethanol infusion was performed (Figure). The left PVs were isolated 30 s after the beginning of the VOM ethanol infusion, and AT was terminated 9 s after the PV isolation. Another two bonus injections of ethanol were administered into more proximal portions of the VOM, following which bidirectional conduction block of the MI was confirmed with a differential pacing technique. There were no complications, and the patient became free from any type of atrial tachyarrhythmia without any antiarrhythmia drugs after a 1-year follow-up. The full-length version of this report can be viewed at: http://www.escardio.org/communities/EHRA/publications/ep-case-reports/ Documents/Simultaneous-re-isolation.pdf. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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1 Department of Cardiovascular Medicine, Hyogo Prefectural Amagasaki Hospital, 1-1-1 Higashidaimotsu, Amagasaki, Hyogo 660-0828, Japan and 2Heart Center, Yokohama-city Bay Red Cross Hospital, Yokohama, Japan
Europace (2014) 16, 1175–1180 doi:10.1093/europace/euu015
Sudden death and ICDs
Sex differences in implantable cardioverterdefibrillator implantation indications and outcomes: lessons from the Nationwide Israeli-ICD Registry Guy Amit 1,2*, Mahmoud Suleiman 3, Yuval Konstantino 1, David Luria 1,4, Mark Kazatsker 5, Israel Chetboun 6, Moti Haim 6, Natalie Gavrielov-Yusim 7, Ilan Goldenberg 7, and Michael Glikson 1,4 On behalf of the Israeli Working Group on Pacing and Electrophysiology 1 Cardiology Department, Soroka Medical Center, Beer-Sheva, Israel; 2Division of Cardiology, Department of Medicine McMaster University, Hamilton General Hospital 237 Barton Street East, Hamilton, ON L8L 2X2, Canada; 3Cardiology Department, Rambam Medical Center, Haifa, Israel; 4Cardiology Department, Sheba Medical Center, Tel Hashomer, Israel; 5 Cardiology Department, Hillel Yafe Hospital, Hadera, Israel; 6Cardiology Department, Meir Hospital, Kfar Saba, Israel; and 7IACT-Neufeld Cardiac Research Institute, Tel Hashomer, Israel
Aims
Implantable cardioverter-defibrillators (ICDs) improve survival in certain high arrhythmic risk populations. However, there are sex differences regarding both the utilization and the benefit of these devices. Using a prospective national ICD registry, we aim to compare the indications for ICD implantation as well as outcomes in implanted women vs. men. ..................................................................................................................................................................................... Methods All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July and results 2010 and February 2013 were included. A total of 3544 subjects constructed the baseline cohort, of whom 615 (17%) were women. Women had the same age (64 years) and rate of secondary prevention indication (26%) as men. However, women were more likely than men to have significant heart failure symptoms (52 vs. 45%), QRS . 120 ms (41 vs. 36%), and a higher rate of non-ischaemic cardiomyopathy (54 vs. 21%, all P values ,0.05). Using multivariate analysis, women were more likely to undergo CRTD implantation (odds ratio ¼ 1.8, P , 0.01). Follow-up data were available for 1518 subjects with a mean follow-up of 12 months. During follow-up, there were no significant differences among genders in the rate of any single or the combined outcomes of appropriate device therapies, heart failure admissions, or death. First-year re-intervention rate was double among women (5.6 vs. 3.0%, P , 0.01). ..................................................................................................................................................................................... Conclusion In real-world setting, women implanted with an ICD differ significantly from men in their baseline characteristics and in the use of CRTD devices. These, however, did not translate into outcome differences.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Implantable cardioverter-defibrillators † Cardiac resynchronization therapy † Women † Outcomes † Registry
Background Numerous studies have consistently shown that implantable cardioverter-defibrillators (ICDs) reduce mortality when used for the primary prevention of sudden cardiac death1 – 3 or for the secondary prevention of such an event.4,5 Accordingly, current practice guidelines6,7 advocate implantation of ICDs according to the characteristics of the populations studied; including those with
previous myocardial infarction (MI) or heart failure (HF) with significantly reduced left ventricular ejection fraction (LVEF) of ,0.30– 0.35, and those who survived life-threatening ventricular arrhythmia such as ventricular tachycardia or fibrillation. Although current guidelines apply to both women and men, there are sex-related differences in the rate of utilization of ICDs. Recent studies suggested that men were three times more likely to receive a device for primary prevention and more than twice for secondary
* Corresponding author. Cardiology Department, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University, POB 151, Beer-Sheva, Israel. Tel: +1 905-527-4322; fax: +1 905-577-1447, E-mail: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
Downloaded from by guest on March 15, 2016
Received 26 July 2013; accepted after revision 16 January 2014; online publish-ahead-of-print 19 February 2014
1176
What’s new? † Women implanted with an implantable cardioverterdefibrillator (ICD) have a higher rate than men of advanced heart failure symptoms. † Women are implanted more often than men with a resynchronization device. † Among the secondary prevention groups, women present more often with ventricular fibrillation rather than ventricular tachycardia. † Women have a higher re-intervention rate than men. † Women implanted with an ICD have same the same shortterm rate of device therapies, heart failure admissions, and death as men.
Methods Study population All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July 2010 and February 2013 were included. The registry was approved by the ethics committee of each participating institution and the patients provided written informed consent. Data were prospectively collected from the index hospitalization at the time of initial ICD implantation or device upgrade by the local electrophysiologist at the implanting centre and entered into a secure, firewall, and password protected web-based electronic case report form. Data collected included demographic, clinical, and procedure-related variables.
Follow-up Follow-up was requested from all centres at a median time of 1 year post-implantation. Mean compliance rate with the follow-up queries was about 50%. Data collected included: the occurrence of death, re-hospitalization for HF or other cardiovascular cause, re-hospitalization for device-related events, and the number and appropriateness of therapies (shock or anti tachycardia pacing) for ventricular tachyarrhythmias.
Statistical analyses Baseline variables were compared using Student’s t-test, analysis of variance, or x2 as appropriate. Logistic regression was used to predict CRTD implantation using gender, New York Heart Association (NYHA) HF class, LVEF, QRS width, implantation indication, and renal function as prespecified covariates. Cox regression was used to assess for independent predictors of mortality, and of appropriate ICD therapy or mortality
during follow-up. Best-fitted stepwise models were built according to the P values of all baseline parameters.
Results Patient population A total of 3544 subjects were included in the baseline cohort, of whom 615 (17%) were women. The mean age was 64 in both the groups. There were significant differences between genders at baseline: coronary artery disease was less prevalent (46 vs. 79%, P , 0.01) and dilated cardiomyopathy was more prevalent (38 vs. 18%, P , 0.01) among women. Likewise, risk factors for coronary disease, including diabetes, hypertension, smoking, and dyslipidaemia were less frequent among women (Table 1). Implanted women had a higher rate of advanced HF, a wider QRS, and a higher proportion of left bundle branch block (LBBB). Women had a lower haemoglobin level and a lower glomerular filtration rate at implantation. Women were treated less frequently with betablockers. The rate of secondary prevention indication for ICD implantation was similar between women and men. However, among the secondary prevention group, documented ventricular fibrillation (VF) was more common (43 vs. 32%), and sustained ventricular tachycardia (VT) was less common (36 vs. 44%) among women (P ¼ 0.01).
Device type Overall, 40% received dual-chamber ICD, 20% received singlechamber ICD, and 40% received CRTD. Women were more likely to undergo CRTD implantation (46 vs. 37%, P , 0.001). Using multivariate analysis, women were almost twice as likely to receive a CRTD device at implantation [odds ratio ¼ 1.8, 95% confidence interval (CI): 1.2 –2.7]. In both women and men, a more advanced NYHA class, a wide QRS, a lower LVEF, primary prevention indication, and age were all independently associated with implantation of a CRTD device; whereas in men, more advanced renal disease was an additional predictor.
Risk of appropriate implantable cardioverter-defibrillator therapy, heart failure hospitalization, or death The follow-up cohort included 1518 patients, of whom 252 (17%) were women. There were no significant baseline differences between the patients with and without follow-up data available. Median follow-up time was 323 days, and the first outcome event was appropriate ICD therapy in 81 subjects (6.1%), HF exacerbation needing admission in 100 subjects (8.1%), and death in 77 subjects (5.4%). Kaplan–Meier survival analysis showed no significant difference between men and women in the cumulative probability for appropriate ICD therapy or death in the whole study cohort, as well as in the primary prevention and the secondary prevention groups (Figure 1A and B, respectively). Similarly, the cumulative probability of HF admission or death during follow-up was not significantly different between men and women receiving both the ICD and the CRTD devices (Figure 2A and B, respectively). Consistent with the univariate findings, multivariate analysis showed that gender was not independently
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prevention,8 and although the rate of ICD utilization among women steadily increased over the years, it is still significantly lower than in men.9 Furthermore, a meta-analysis found no survival benefit for ICDs in women with HF and primary prevention indication.10 Thus, there is an urgent need to further elucidate the benefits and harms of ICDs among women. The Israeli ICD registry is a prospective nationwide database of all ICD implants. Herein, we aim at comparing the indication for ICD implantation as well as the outcome in women vs. men in a reallife scenario.
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Table 1 Comorbidities, baseline, and device characteristics according to gender N (%)
Women N 5 615
Men N 5 2927
P value
............................................................................................................................................................................... Age mean + SD
64 + 14
64 + 13
0.19
Diabetes
192 (31)
1075 (37)
,0.01
Hypertension Dyslipidaemia
346 (57) 288 (47)
1864 (64) 1618 (56)
,0.01 ,0.01
74 (12)
1014 (35)
,0.01
Atrial fibrillation Ischaemic cardiomyopathy
123 (20) 282 (46)
620 (21) 2305 (79)
0.49 ,0.01
Dilated cardiomyopathy
234 (38)
529 (18)
,0.01
62 (11)
166 (6)
Smoking
Left ventricular ejection fraction Normal (≥50%) Mild dysfunction (40–49%)
,0.01 30 (5)
161 (6)
161 (28) 320 (56)
937 (34) 1525 (54)
I II
36 (8) 192 (40)
233 (10) 1037 (45)
III
242 (51)
1022 (44)
Moderate dysfunction (30– 39%) Severe dysfunction (,30%) HF; NYHA class
0.02
8 (1) 120 + 32
27 (1) 118 + 30
0.05
QRS ≥ 120 ms:
251 (41%):
1059 (36%):
0.03
LBBB morphology Haemoglobin level (g/dL) at implantation, median
209 (83%) 12.4
798 (75%) 13.2
0.04 ,0.01
Glomerular filtration rate (mL/min), median Medications ACEI/ARB
67
71
,0.01
435 (71)
2156 (75)
0.08
Beta-blockers
472 (77)
2380 (82)
,0.01
Diuretics Antiarrhythmics
436 (71) 99 (16)
2040 (70) 514 (18)
0.69 0.35
79 (20)
397 (22)
0.42 0.82
Coumadin ICD implantation indication Secondary prevention of sudden death
160 (26):
749 (26):
Resuscitated VF
69 (43)
241 (32)
Spontaneous sustained VT Syncope/unknown aetiology
58 (36) 26 (23)
332 (44) 137 (24)
0.01 ,0.01
Device type Single chamber Dual chamber
117 (19) 218 (35)
623 (21) 1215 (42)
Cardiac resynchronization
280 (46)
1089 (37)
NYHA, New York Heart Association; ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker.
associated with increased risk of all-cause mortality, HF admissions, appropriate ICD therapy, mortality, or combinations of the above, after further adjustment for age, device-type, LVEF, implantation indication, diabetes, use of beta-blockers, and renal function (Table 2).
replacement) and 5 system removals. The re-intervention rate was significantly higher among women vs. men (5.6 vs. 3.0%, P ¼ 0.02). These rates were 4.4 vs. 2.6% (P ¼ 0.24), and 6.9 vs. 3.7% (P ¼ 0.13), among the ICD and the CRTD groups, respectively.
Re-intervention rate
Discussion
There were 52 re-interventions during the first year in the follow-up cohort (3.4%) including 45 lead-related procedures (reposition/
Using a nationwide comprehensive ICD registry, we found the following major findings: there are significant differences in the clinical
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IV QRS duration (ms) + SD
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G. Amit et al.
P (log rank) = 0.65
A
P (log rank) = 0.39
B
90
90 Survival (%)
100
Survival (%)
100
80 70 60
80 70 60
Male Female
50
Male Female
50 0
50 100 150 200 250 300 350 400 450 500 Time (days)
0
50 100 150 200 250 300 350 400 450 500 Time (days)
Figure 1 Time to appropriate ICD therapy or death by gender among primary (A) and secondary (B) prevention subjects.
P (log rank) = 0.84
A
P (log rank) = 0.64
B
90
90
80 70 60
80 70 60
Male Female
50
Male Female
50 0
50 100 150 200 250 300 350 400 450 500 Time (days)
0
50 100 150 200 250 300 350 400 450 500 Time (days)
Figure 2 Time to HF admission or death by gender in ICD (A) and CRTD (B) recipients.
Table 2 The impact of gender on different outcomes HR
95% CI
P value
0.83 1.17
0.44– 1.81 0.54– 2.54
0.64 0.69
................................................................................ Death Appropriate therapy HF admission
0.81
0.41– 1.60
0.55
Death or appropriate therapy Death or HF admission
1.03 0.85
0.60– 1.77 0.51– 1.41
0.92 0.53
Data shown are hazard ratios (HRs) in women vs. men adjusted for age, LVEF, CRT, implantation indication, diabetes, use of beta-blockers, and renal function.
characteristics between men and women who receive a device in a real-world setting; women have a higher proportion of nonischaemic cardiomyopathy, and are more likely to be implanted with a CRTD device. Among women implanted for secondary prevention of sudden death, the presenting arrhythmia is more often VF than sustained VT. However, those baseline and
device-type-related differences did not translate into significant gender-related differences in the risk of all-cause mortality, appropriate ICD therapy, or HF admission rates, during follow-up. On the other hand women had a significantly higher re-intervention rate than men. The relatively lower rate of coronary artery disease among implanted women, partially explains the lower participation rate of women in some of the primary prevention studies. Thus, in trials of post-MI patients such as the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II)2 women comprised only 15% of the population studied. This contrasts with the HF studies; in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT),3 where about half of the subjects had non-ischaemic cardiomyopathy, women comprised 24% of the population. Likewise, in the Ontario database,11 where 21% of ICD implants were in women, men had a significantly higher rate of atherosclerosis risk factors and past coronary artery interventions. Furthermore, not only the aetiology of the cardiac disease is different among genders, implanted women have a higher rate of advanced HF, bundle branch blocks, and longer QRS, and therefore are implanted more often with CRTD devices.
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Survival (%)
100
Survival (%)
100
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Study limitations include the inherent limitations of a registry, mainly quality and completeness of the data. Although several quality assurance algorithms were applied in the patient registration phase, some devices were probably missed from the national registry. In addition, follow-up information regarding therapies given by the device and readmission rates were reported by the implanting facility following queries sent to 1 year after implantation. It was the implanting physician responsibility to see the patient/medical chart, interrogate the device, and answer the query in a timely manner. If not answered, the queries were re-sent. However, even after adding a phone and an e-mail-based notification system, the response rates varied significantly between the implanting hospitals, and averaged 50%. However, to see whether the response rate introduces a bias regarding our follow-up results (e.g. overemphasizing sicker population with more physician follow-ups), we analysed the baseline characteristics of patients with and without follow-up data were available. No statistical differences were found regarding the basic demographics, co-morbidities, or implant types between the two groups. Therefore, we believe our follow-up data results are valid. In conclusion, in real-world setting, women implanted with an ICD differ significantly from men in baseline characteristics and in the use of CRTD devices. These, however, did not translate to outcome differences. Conflict of interest: none declared.
Funding This work was supported by an unrestricted research grant from Boston Scientific to the Israeli Working Group on Electrophysiology and the Israeli Association for Cardiovascular Trials.
References 1. Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H et al. Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933 –40. 2. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877 –83. 3. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225–37. 4. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337: 1576 –83. 5. Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS et al. Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297 –302. 6. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA III, Freedman RA, Gettes LS et al. ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/ AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51: e1 –62. 7. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M et al. ACC/ AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace 2006;8:746 –837.
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Since the rate of non-ischaemic cardiomyopathy is higher in women than men, and since current primary prevention guidelines advocate that ICD implantation in this population will be based upon HF symptoms, it is not surprising that in real life, women with ICDs are found to have an overall higher rate of HF symptoms, and thus a higher rate of CRTD implantations. There were no significant gender differences in the distribution of primary vs. secondary implantation indication. However, among the secondary prevention subset, women were more often diagnosed with VF than monomorphic VT, probably reflecting the different myocardial pathologies. That is, the baseline differences found in the aetiology of the cardiac disease that led to ICD implantation (i.e. ischaemic vs. non-ischaemic cardiomyopathy) also point to a different arrhythmogenic substrate (monomorphic VT being more prevalent than VF among the post-MI-ischaemic cardiomyopathy patients).12 Even so, at follow-up, we did not observe a significant gender difference in the rate of appropriate therapies or death. These finding contrasts with previous reports which found 31% less appropriate shocks in women over 1 year9 or an analogous two- to three-fold increased hazard for such events in men.8 Both studies did not find a mortality difference between men and women, although one meta-analysis found no ICD survival benefit in women.10 Our lack of association between gender and ICD therapies/death can be attributed to the contemporary programming of the devices, in which slow and non-sustained tachycardias are not treated and therefore the overall rate of treated monomorphic VT events is lower than in previous studies. In addition, no gender differences were found relating to HF admissions both in the ICD and the CRTD group. In contrast to the previous small-scale studies, the MADIT-CRT trial demonstrated significant mortality and HF admissions reduction in women vs. men with CRTD devices, which was attributed to a higher incidence of LBBB and non-ischaemic cardiomyopathy among women.13 Furthermore, the investigators also found, that a greater sex-related difference in responses to CRT was evident in the subgroup of patients with non-ischaemic cardiomyopathy.14 However, in the SMART-AV study, women had a better response to CRT even after adjustment for baseline variables such as ischaemic vs. nonischaemic cardiomyopathy and LBBB.15 According to our data, and given their worse baseline CHF status, women were expected to have higher mortality and HF rates over follow-up. The higher rate of CRT use can partially explain the equal rates of events between genders. Other explanations can be the more benign course of nonischaemic cardiomyopathy, and the relatively short follow-up time. Re-intervention rate was double in women in our registry, where the most common procedure was lead repositioning or replacement. The same pattern was detected in both CRTD and non-CRTD implants, implying that the difference was not due to the higher CRTD rate among women. In the Ontario registry,11 an increase rate of complications were observed in women, an observation reported also in the American national cardiovascular data registry.16 One explanation could be the higher rate of CRTD use among the registry women: using more leads and especially coronary sinus leads predisposes the patient to more lead complications. We can also speculate that some lead designs might be more suitable for men than for women due to intrinsic properties (e.g. weight, screw length, etc.).
1180 8. Curtis LH, Al-Khatib SM, Shea AM, Hammill BG, Hernandez AF, Schulman KA. Sex differences in the use of implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death. JAMA 2007;298:1517 –24. 9. MacFadden DR, Tu JV, Chong A, Austin PC, Lee DS. Evaluating sex differences in population-based utilization of implantable cardioverter-defibrillators: role of cardiac conditions and noncardiac comorbidities. Heart Rhythm 2009;6:1289 –96. 10. Ghanbari H, Dalloul G, Hasan R, Daccarett M, Saba S, David S et al. Effectiveness of implantable cardioverter defibrillators for the primary prevention of sudden cardiac death in women with advanced heart failure: a meta-analysis of randomized controlled trials. Arch Intern Med 2009;169:1500 –6. 11. MacFadden DR, Crystal E, Krahn AD, Mangat I, Healey JS, Dorian P et al. Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database. Ann Intern Med 2012;156:195 –203. 12. Attin M, Ideker RE, Pogwizd SM. Mechanistic insights into ventricular arrhythmias from mapping studies in humans. Heart Rhythm 2008;5(suppl):S53– 8.
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13. Arshad A, Moss AJ, Foster E, Padeletti L, Barsheshet A, Goldenberg I et al. MADIT-CRT Executive Committee. Cardiac resynchronization therapy is more effective in women than in men: the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) trial. J Am Coll Cardiol 2011;57:813 –20. 14. Barsheshet A, Brenyo A, Goldenberg I, Moss AJ. Sex-related differences in patients’ responses to heart failure therapy. Nat Rev Cardiol 2012;9:234 –42. 15. Cheng A, Gold MR, Waggoner AD, Meyer TE, Seth M, Rapkin J et al. Potential mechanisms underlying the effect of gender on response to cardiac resynchronization therapy: insights from the SMART-AV multicenter trial. Heart Rhythm 2012;9: 736 –41. 16. Peterson PN, Daugherty SL, Wang Y, Vidaillet HJ, Heidenreich PA, Curtis JP et al. National Cardiovascular Data Registry. Gender differences in procedure-related adverse events in patients receiving implantable cardioverter-defibrillator therapy. Circulation 2009;119:1078 –84.
EP CASE EXPRESS
doi:10.1093/europace/euu060 Online publish-ahead-of-print 27 March 2014
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Simultaneous re-isolation of the left pulmonary veins and termination of peri-mitral flutter with only an ethanol infusion in the vein of Marshall: killing two birds with one stone Kazuyasu Yoshitani1*, Kazuto Kujira1, and Kaoru Okishige2
* Corresponding author. Tel: +81 6 6482 1521; fax: +81 6 6482 7430. E-mail: [email protected]
A 65-year-old male patient was admitted for ablation of a recurrent atrial A B C tachycardia (AT) after a previous ablation of persistent atrial fibrillation that consisted of a bilateral pulmonary vein (PV) isolation, electrogram-based ablation, and linear ablation at the mitral isthmus (MI) and cavotricuspid isthmus. During the index procedure, bidirectional block of the MI could D not be achieved in spite of a meticulous endocardial radiofrequency ablation as well as from inside the coronary sinus. In the second procedure, a recurrent perimitral AT and reconnection of the left PVs were confirmed. Then a vein of Marshall (VOM) ethanol infusion was performed (Figure). The left PVs were isolated 30 s after the beginning of the VOM ethanol infusion, and AT was terminated 9 s after the PV isolation. Another two bonus injections of ethanol were administered into more proximal portions of the VOM, following which bidirectional conduction block of the MI was confirmed with a differential pacing technique. There were no complications, and the patient became free from any type of atrial tachyarrhythmia without any antiarrhythmia drugs after a 1-year follow-up. The full-length version of this report can be viewed at: http://www.escardio.org/communities/EHRA/publications/ep-case-reports/ Documents/Simultaneous-re-isolation.pdf. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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1 Department of Cardiovascular Medicine, Hyogo Prefectural Amagasaki Hospital, 1-1-1 Higashidaimotsu, Amagasaki, Hyogo 660-0828, Japan and 2Heart Center, Yokohama-city Bay Red Cross Hospital, Yokohama, Japan
