Vol 30, No 2 (2023)
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Prognostic impact of age and gender on patients with electrical storm

Kathrin Weidner12, Tobias Schupp12, Jonas Rusnak12, Julian Mueller12, Gabriel Taton12, Linda Reiser12, Armin Bollow12, Thomas Reichelt12, Dominik Ellguth12, Niko Engelke12, Max Barre12, Dirk Große Meininghaus3, Jorge Hoppner4, Ibrahim El-Battrawy12, Kambis Mashayekhi5, Ibrahim Akin12, Michael Behnes12
Pubmed: 36651569
Cardiol J 2023;30(2):204-213.

Abstract

Background: Electrical storm (ES) is a severe and life-threatening heart rhythm disorder. Age and
male gender have been identified as independent risk factors for cardiovascular diseases. However, data
regarding the prognostic impact of age and gender on ES patients is limited.
Methods: The present study included retrospectively consecutive patients presenting with ES from
2002 to 2016. Patients 67 years old or older were compared to patients younger than 67, males were
also compared to females. Receiver operating characteristic analyses were performed to find the optimum
age cut-off value. The primary endpoint was all-cause mortality at 3 years. The secondary endpoints
were in-hospital mortality, rehospitalization rates, ES recurrences, and major adverse cardiac events
(MACE) at 3 years.
Results: Eighty-seven ES patients with implantable cardioverter-defibrillators were included. Age ≥ 67
years was associated with increased all-cause mortality at 3 years (48% vs. 20%, hazard ratio = 3.046;
95% confidence interval 1.316–7.051; p = 0.008; log-rank p = 0.006). MACE, in-hospital mortality, rehospitalization
rates, and ES recurrences were not affected by age. Even after multivariate adjustment, age
≥ 67 years was associated with increased long-term mortality at 3 years, besides left ventricular ejection
fraction < 35%. In contrast, gender was not associated with primary and secondary endpoints.
Conclusions: Patients 67 years old and older presenting with ES are associated with poor long-term
prognosis. Increased long-term mortality was still evident after multivariate adjustment. In contrast,
gender was not associated with primary and secondary endpoints.

clinicAL CARDIOLOGY

Original Article

Cardiology Journal

2023, Vol. 30, No. 2, 204–213

DOI: 10.5603/CJ.a2023.0003

Copyright © 2023 Via Medica

ISSN 1897–5593

eISSN 1898–018X

Prognostic impact of age and gender on patients with electrical storm

Kathrin Weidner12Tobias Schupp12Jonas Rusnak12Julian Mueller12Gabriel Taton12Linda Reiser12Armin Bollow12Thomas Reichelt12Dominik Ellguth12Niko Engelke12Max Barre12Dirk Große Meininghaus3Jorge Hoppner4Ibrahim El-Battrawy12Kambis Mashayekhi5Ibrahim Akin12Michael Behnes12
1Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
2European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
3Department of Cardiology, Carl-Thiem-Klinikum Cottbus, Germany
4Department of Nuclear Medicine, University Hospital Heidelberg, Germany
5Department of Cardiology and Angiology II, University Heart Center Freiburg, Bad Krozingen, Germany

Address for correspondence: Prof. Dr. med. Michael Behnes, First Department of Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany, tel: +49 621 383 6239, e-mail: michael.behnes@umm.de

Received: 8.07.2022 Accepted: 21.10.2022 Early publication date: 16.01.2023

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

Abstract

Background: Electrical storm (ES) is a severe and life-threatening heart rhythm disorder. Age and male gender have been identified as independent risk factors for cardiovascular diseases. However, data regarding the prognostic impact of age and gender on ES patients is limited.

Methods: The present study included retrospectively consecutive patients presenting with ES from 2002 to 2016. Patients 67 years old or older were compared to patients younger than 67, males were also compared to females. Receiver operating characteristic analyses were performed to find the optimum age cut-off value. The primary endpoint was all-cause mortality at 3 years. The secondary endpoints were in-hospital mortality, rehospitalization rates, ES recurrences, and major adverse cardiac events (MACE) at 3 years.

Results: Eighty-seven ES patients with implantable cardioverter-defibrillators were included. Age ≥ 67 years was associated with increased all-cause mortality at 3 years (48% vs. 20%, hazard ratio = 3.046; 95% confidence interval 1.316–7.051; p = 0.008; log-rank p = 0.006). MACE, in-hospital mortality, rehospitalization rates, and ES recurrences were not affected by age. Even after multivariate adjustment, age ≥ 67 years was associated with increased long-term mortality at 3 years, besides left ventricular ejection fraction < 35%. In contrast, gender was not associated with primary and secondary endpoints.

Conclusions: Patients 67 years old and older presenting with ES are associated with poor long-term prognosis. Increased long-term mortality was still evident after multivariate adjustment. In contrast, gender was not associated with primary and secondary endpoints. (Cardiol J 2023; 30, 2: 204–213)

Key words: electrical storm, age, gender, long-term mortality

Introduction

Electrical storm (ES) is a severe heart rhythm disorder defined as at least three distinct episodes of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) within 24 hours (separated by at least 5 min), requiring termination by an intervention [1, 2]. ES is associated with increased mortality of 40% at 1 year [3]. The clinical presentation varies between asymptomatic patients and those with severe hemodynamic instability or cardiac death [4]. Therefore, therapeutic options are diverse and include pharmacotherapy to reduce sympathetic system tension (first-line therapy beta-blockers), device therapy (overdrive stimulation, antitachycardia pacing, internal high voltage therapy), external cardioversion or defibrillation, rescue ablation of VT, and extracorporeal membrane oxygenation or intra-aortic balloon pump [1, 3]. Individually tailored therapy risk stratification is needed in this high-risk cohort and might improve patient outcomes [3].

The population of elderly patients is increasing in Europe [5]. Advanced age is the main risk factor for vascular disease [6]. The incidence of ventricular tachyarrhythmias (VTA) increases with age and is mostly attributed to higher rates of structural heart disease in the elderly, like ischemic or hypertensive cardiomyopathy [5, 7]. The treatment of VTA in elderly patients is a severe clinical challenge. Adverse effects of antiarrhythmic drugs have been frequently seen in elderly patients. These side effects are mostly attributed to decreased physiological function, side effects of polypharmacy, and geriatric syndromes [8, 9].

Male gender is an established risk factor for the future development of cardiovascular disease (CVD) [10]. Steroid hormones like estrogen and progesterone influence gender-related cardiovascular risk profiles [11]. It has been shown that steroid hormones affect blood pressure regulation, blood flow, vasodilatation, vascular inflammation, and atherosclerosis [11]. However, prior studies have reported an absence of these effects in postmenopausal women [12].

The prognostic impact of age and gender on ES patients has been investigated very little. Although advanced age is a known cardiovascular risk factor, elderly patients are usually excluded from most randomized controlled trials [13]. It is essential to identify clinical risk factors that impact ES patients’ long-term prognosis to reduce morbidity and mortality.

Therefore, the present longitudinal, observational, registry-based, monocentric cohort study investigates the prognostic impact of age ≥ 67 years and gender on long-term all-cause mortality, major adverse cardiac events (MACE), in-hospital mortality, rehospitalization rates, and recurrences of ES (ES-R) in patients presenting with ES.

Methods

Study population

All consecutive patients with implantable cardioverter-defibrillator (ICD) referred to our institution with an ES diagnosis between 2002 and 2016 were included. ES was defined as three or more episodes of VTA, delimited by at least 5 minutes, leading to appropriate ICD therapy during a single 24-hour time period [1]. Only ICD recipients were included. All relevant clinical data were documented using the electronic hospital information system, ICD protocols, discharge letters, daily charts, patient files, and reports from diagnostic testing, including 12-lead electrocardiogram (ECG) and Holter ECG assessed during the clinical routine.

In detail, data documentation included baseline characteristics, prior medical history, prior medical treatment, length of index stay, detailed findings of laboratory values at baseline, data derived from all non-invasive or invasive cardiac diagnostics and device therapies like coronary angiography and electrophysiological examination, and imaging modalities like echocardiography or cardiac magnetic resonance imaging. The documentation period lasted from the index event until 2016. Independent cardiologists blinded to final data analyzes performed all medical data documentation at the time of the patient’s individual clinical presentation period.

The present study is derived from a retrospective analysis of the Registry of Malignant Arrhythmias and Sudden Cardiac Death–Influence of Diagnostics and Interventions (RACE-IT) and represents a single-center registry that includes consecutive patients presenting with VTA and aborted cardiac arrest and acutely admitted to the University Medical Center Mannheim, Germany (clinicaltrials.gov identifier: NCT02982473) from 2002 until 2016. The registry was carried out according to the principles of the Declaration of Helsinki. It was approved by the medical ethics committee II of the Faculty of Medicine Mannheim, University of Heidelberg, Germany.

Definition of study groups, inclusion and exclusion criteria

Risk stratification was performed according to age and gender. Only patients who already had an ICD and presented with ES were analyzed. Receiver operating characteristic (ROC) analyzes were performed to find the highest Youden index. The Youden index, defined as the maximum of sensitivity + specificity –1, was used to find the optimum age cut-off for the present study [14, 15]. Furthermore, males were compared to females. Each patient was counted only once for inclusion when presenting with the first episode of ES.

Study endpoints

The primary endpoint was all-cause mortality at a follow-up of 3 years. Secondary endpoints were in-hospital mortality, first cardiac rehospitalization, MACE, and ES-R at long-term follow-up of 3 years. First cardiac rehospitalization was related to recurrent VT and VF, excluding ES-R, and to cardiopulmonary resuscitation, acute heart failure, or acute myocardial infarction (AMI). AMI patients included those with both ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction according to current guidelines [16]. In addition, the coronary angiography results at index stay were retrieved to update these patients’ coronary artery disease diagnoses. MACE was defined as the composite of AMI, target vessel revascularization by percutaneous coronary intervention or coronary artery bypass grafting, and the primary endpoint of all-cause mortality [16]. ES-R was defined as the recurrence of further ES episodes at follow-up beyond the initial 24 hours of prior ES [2]. The follow-up period lasted until 2016. All-cause mortality was documented using our electronic hospital information system and by directly contacting state resident registration offices (Bureau of mortality statistics) across Germany. Patient identity was verified by name, surname, date of birth, and registered living address.

Statistical methods

Quantitative data are presented as mean ± standard error of mean, median, and interquartile range and ranges, depending on the data distribution, and were compared using the Student t-test for normally distributed data or the Mann–Whitney U test for nonparametric data. The Kolmogorov–Smirnov test tested deviations from a Gaussian distribution. The Spearman rank correlation for nonparametric data was used to test univariate correlations. Qualitative data are presented as appropriate and relative frequencies and were compared using the c2 test or the Fisher exact test.

Multivariate Cox regression models were developed using the “forward selection” option, where only statistically significant variables (p < 0.05) were included and analyzed simultaneously (see below). The following analyzes were applied stepwise to evaluate the prognostic value of predefined variables for all-cause mortality: Kaplan-Meier survival curves were calculated with log-rank testing for statistical significance. Univariate hazard ratios (HR) are given with 95% confidence intervals (CI). Multivariate Cox regressions were applied for age analyzes only because of an assumed higher event rate for the primary endpoint. Predefined variables used for the multivariate Cox regressions included age ≥ 67 years, male gender, coronary artery disease, atrial fibrillation, left ventricular ejection fraction (LVEF) < 35%, beta-blocker, and, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). The result of a statistical test was considered significant for p < 0.05. SAS, release 9.4 (SAS Institute Inc., Cary, NC, USA) was used for statistics.

Results

Study population by age < 67 years and ≥ 67 years

Eighty-seven consecutive patients with ES at index were included in the present study. The maximum Youden index was 0.353 for a cut-off at 67 years. Therefore, patients 67 years old and older were compared to patients younger than 67 years old. Of these, 40% were younger than 67, and 60% were 67 or older. As outlined in Table 1, most patients were male, and significantly more patients 67 years old or older suffered from arterial hypertension (73% vs. 49%; p = 0.020). Furthermore, patients 67 years old or older had a significantly lower LVEF (79% vs. 53%, p = 0.042) and higher rates of ischemic cardiomyopathy (52% vs. 46%, p = 0.016). Notably, all patients 67 years old and older were treated with beta-blockers at discharge (100% vs. 87%, p = 0.015). No other differences were seen between these patient groups (Table 1).

Table 1. Baseline characteristics of patients presenting with electrical storm by age < 67 years and ≥ 67 years.

Characteristic

Age < 67 years (n = 35; 40%)

Age 67 years (n = 52; 60%)

P

Age, [year] median (range)

56 (22–67)

77 (68–85)

0.001

Male gender

28 (80%)

46 (89%)

0.278

Cardiopulmonary resucitation:

2 (6%)

3 (6%)

0.991

Out-of-hospital

1 (3%)

2 (4%)

0.999

In-hospital

1 (3%)

1 (2%)

0.775

Cardiovascular risk factors:

Arterial hypertension

17 (49%)

38 (73%)

0.020

Diabetes mellitus

6 (17%)

16 (31%)

0.152

Hyperlipidemia

11 (31%)

26 (50%)

0.086

Smoking

9 (26%)

6 (12%)

0.086

Cardiac family history

2 (6%)

5 (10%)

0.512

Comorbidities:

Acute myocardial infarction

0 (0%)

0 (0%)

Chronic kidney disease

8 (30%)

22 (51%)

0.076

Atrial fibrillation

12 (34%)

24 (46%)

0.270

Liver cirrhosis

1 (3%)

2 (4%)

0.804

COPD

3 (9%)

12 (23%)

0.079

Prior stroke

6 (17%)

6 (12%)

0.917

Cardiomyopathy:

Ischemic cardiomyopathy

16 (46%)

27 (52%)

0.016

Non-ischemic cardiomyopathy

3 (9%)

5 (10%)

0.868

Not documented

15 (14%)

20 (39%)

0.681

Channelopathies:

Long-QT syndrome

1 (3%)

0 (0%)

0.402

Brugada syndrome

1 (3%)

0 (0%)

0.402

Short-QT syndrome

0 (0%)

0 (0%)

Coronary angiography:

24 (69%)

43 (83%)

0.124

No coronary artery disease

8 (33%)

6 (14%)

0.257

Coronary one vessel disease

4 (17%)

7 (17%)

Coronary two vessel disease

6 (25%)

12 (28%)

Coronary three vessel disease

6 (25%)

18 (27%)

Electophysiological examination:

10 (29%)

11 (21%)

0.428

VT ablation

9 (26%)

9 (17%)

0.343

Laboratory data:

Hemoglobin [g/dL]

13.7 ± 0.3

12.7 ± 0.3

0.778

Potassium [mmol/L]

3.9 ± 0.1

4.1 ± 0.1

0.282

Creatinine [mg/dL]

1.2 ± 0.08

1.5 ± 0.1

0.403

Urea [mg/dL]

83.0 ± 12.0

88.0 ± 14.0

0.673

C-reactive protein [mg/dL]

20.9 ± 6.6

35.2 ± 8.7

0.197

Troponin I [µg/L]

0.4 ± 0.1

0.2 ± 0.0

0.128

Medication at discharge:

Beta-blocker

31 (87%)

49 (100%)

0.015

ACE inhibitor/ARB

28 (80%)

39 (80%)

0.963

Statin

19 (54%)

31 (63%)

0.408

Amiodarone

16 (46%)

29 (59%)

0.222

ECG data

PQ [ms]

240 ± 60

216 ± 10

0.015

QRS [ms]

120 ± 20

129 ± 15

0.401

QT [ms]

435 ± 19

442 ± 19

0.090

LVEF:

0.042

≥ 55%

7 (21%)

2 (4%)

45–54%

4 (13%)

3 (6%)

35–44%

4 (13%)

5 (10%)

< 35%

17 (53%)

38 (79%)

Type of ICD:

0.170

ICD

32 (91%)

44 (85%)

CRT-D

1 (3%)

7 (14%)

s-ICD

2 (6%)

1 (2%)

ICD indication:

0.071

Primary prevention

17 (49%)

15 (29%)

Secondary prevention

18 (51%)

36 (71%)

ICD programming [bpm], median (IQR):

VT detection threshold

169 (128–220)

165 (133–188)

0.382

VF detection threshold

217 (200–250)

219 (200–250)

0.486

Study population in patients by gender

Of the 87 patients included in this study, 15% were female, and 85% were male. As outlined in Table 2, in-hospital cardiac arrest was more frequent in females (15% vs. 1%, p = 0.010). Differences between males and females were found in ECG data. Female patients showed a significantly longer QT interval (400 ± 0 vs. 448 ± 15, p = 0.002) (Table 2). No other differences were seen between the two groups (Table 2).

Table 2. Baseline characteristics of female and male patients presenting with electrical storming.

Characteristic

Female (n = 13; 15%)

Male (n = 74; 85%)

P

Age [year], median (range)

65 (52–83)

72 (22–85)

0.414

Cardiopulmonary resucitation:

3 (23%)

5 (7%)

0.744

Out-of-hospital

1 (8%)

4 (5%)

0.743

In-hospital

2 (15%)

1 (1%)

0.010

Cardiovascular risk factors:

Arterial hypertension

11 (85%)

44 (60%)

0.083

Diabetes mellitus

4 (31%)

18 (24%)

0.622

Hyperlipidemia

7 (54%)

30 (40%)

0.371

Smoking

0 (0%)

15 (20%)

0.074

Cardiac family history

2 (15%)

5 (7%)

0.292

Comorbidities:

Acute myocardial infarction

0 (0%)

0 (0%)

Chronic kidney disease

6 (46%)

24 (32%)

0.337

Atrial fibrillation

7 (54%)

29 (39%)

0.322

Liver cirrhosis

1 (8%)

3 (4%)

0.563

COPD

2 (15%)

13 (18%)

0.847

Prior stroke

2 (15%)

12 (16%)

0.940

Cardiomyopathy:

Ischemic cardiomyopathy

5 (38%)

36 (48%)

0.443

Non-ischemic cardiomyopathy

1 (8%)

8 (11%)

0.733

Not documented

7 (54%)

30 (41%)

0.370

Channelopathies:

Long-QT syndrome

1 (8%)

0 (0%)

1.000

Brugada syndrome

0 (0%)

1 (1%)

1.000

Short-QT syndrome

0 (0%)

0 (0%)

Coronary angiography at index:

12 (92%)

54 (73%)

0.132

No coronary artery disease

4 (33%)

10 (18%)

0.664

Coronary one vessel disease

2 (17%)

9 (16%)

Coronary two vessel disease

3 (25%)

15 (27%)

Coronary three vessel disease

3 (25%)

21 (39%)

Electophysiological examination:

1 (8%)

20 (27%)

0.133

VT ablation

1 (8%)

17 (23%)

0.210

Laboratory data:

Hemoglobin [g/dL]

12.3 ± 0.5

13.3 ± 0.2

0.194

Potassium [mmol/L]

4.0 ± 0.2

4.0 ± 0.08

0.513

Creatinine [mg/dL]

1.4 ± 0.1

1.4 ± 0.08

0.861

Urea [mg/dL]

87.2 ± 6.5

87.2 ± 13.7

0.289

C-reactive protein [mg/dL]

61.9 ± 18.5

24.5 ± 6.0

0.187

Troponin I [µg/L]

0.3 ± 0.1

0.3 ± 0.06

0.462

Medication at discharge:

Beta-blocker

13 (100%)

68 (94%)

0.403

ACE inhibitor/ARB

10 (83%)

57 (79%)

0.739

Statin

7 (58%)

43 (60%)

0.928

Amiodarone

6 (50%)

39 (54%)

0.789

ECG data:

PQ [ms]

220 ± 40

220 ± 10

0.055

QRS [ms]

113 ± 13

134 ± 18

0.256

QT [ms]

400 ± 0

448 ± 15

0.002

LVEF:

0.727

≥ 55%

2 (15%)

7 (10%)

45–54%

2 (15%)

5 (8%)

35–44%

1 (8%)

8 (12%)

< 35%

8 (62%)

47 (70%)

Type of ICD:

0.654

ICD

11 (85%)

65 (88%)

CRT-D

1 (8%)

7 (10%)

s-ICD

1 (8%)

2 (3%)

ICD indication:

0.919

Primary prevention

5 (39%)

27 (37%)

Secondary prevention

8 (61%)

46 (63%)

ICD programming [bpm], median (IQR):

VT detection threshold

171 (136–220)

165 (128–188)

0.410

VF detection threshold

217 (200–250)

218 (200–250)

0.703

Primary and secondary endpoints by age < 67 years and ≥ 67 years

Follow-up for all patients regarding the primary endpoint of all-cause mortality was performed at 3 years (median 2.45 years, interquartile range 1.01–4.77 years), with at least one ICD check-up regularly every 6 to 12 months. Patients 67 years old and older were associated with the primary endpoint of all-cause mortality at 3 years (48% vs. 20%, HR = 3.046; 95% CI 1.316–7.051; p = = 0.008; log-rank p = 0.006) (Table 3; Fig. 1A) but not with MACE (48% vs. 29%, HR = 2.034; 95% CI 0.976–4.238; p = 0.069; log-rank p = 0.053) (Table 3; Fig. 1B), in-hospital mortality (4% vs. 0%, p = 0.513), first cardiac rehospitalization (38% vs. 51%, p = 0.231), or ES-R (31% vs. 17%, p = 0.152) (Table 3).

Table 3. Primary and secondary endpoints of patients with electrical storm, by age < 67 and ≥ 67 years.

Characteristic

Age < 67 years (n = 35; 40%)

Age 67 years (n = 52; 60%)

P

Primary endpoint

All-cause mortality at 3 years

7 (20%)

25 (48%)

0.008

Secondary endpoints

In-hospital mortality

0 (0%)

2 (4%)

0.513

First cardiac rehospitalization

18 (51%)

20 (38%)

0.231

Major adverse cardiac event

10 (29%)

25 (48%)

0.069

Electricial storm-recurrence

6 (17%)

16 (31%)

0.152

Figure 1. Prognostic impact of age on long-term all-cause mortality at long-term follow-up of 3 years (A) and major adverse cardiac events (MACE) (B).
Primary and secondary endpoints by gender

The primary and secondary endpoints were not affected by gender (Table 4; Fig. 2).

Table 4. Primary and secondary endpoints in female and male patients with electrical storm.

Characteristic

Female (n = 13; 15%)

Male (n = 74; 85%)

P

Primary endpoint

All-cause mortality

5 (39%)

27 (37%)

0.892

Secondary endpoints

In-hospital mortality

0 (0%)

2 (3%)

0.549

First cardiac rehospitalization

5 (38%)

33 (45%)

0.680

Major adverse cardiac event

6 (46%)

29 (39%)

0.637

Electricial storm-recurrence

2 (15%)

20 (27%)

0.376

Figure 2. Prognostic impact of gender on long-term all-cause mortality at long-term follow-up of 3 years.
Multivariate Cox regression by age < 67 years and ≥ 67 years

Even after multivariate adjustment, age ≥ 67 years was associated with increased long-term mortality at 3 years (HR = 4.267, 95% CI 1.057–8.277, p = 0.039), besides LVEF < 35% (HR = 10.341, 95% CI 2.127–50.26, p = 0.004). The presence of beta-blockers (HR = 0.119, 95% CI 0.017–0.825, p = 0.031) and ACE inhibitors or ARBs at discharge (HR = 0.345, 95% CI 0.143–0.831, p = 0.018) was beneficial (Table 5).

Table 5. Multivariable Cox regression analyses.

Endpoint

All-cause mortality at 3 years

HR

95% CI

P

Age ≥ 67 years

4.267

1.057–8.277

0.039

Male gender

0.407

0.135–1.223

0.109

CAD

0.977

0.398–2.494

0.995

Atrial fibrillation

1.115

0.523–2.377

0.778

LVEF < 35%

10.341

2.127–50.26

0.004

Beta-blocker

0.119

0.017–0.825

0.031

ACE-inhibitor/ARB

0.345

0.143–0.831

0.018

Discussion

The present study evaluates the prognostic impact of age and gender in consecutive high-risk patients presenting with ES on admission. The data suggest that ES patients 67 years old or older have higher long-term mortality at 3 years than younger patients. In-hospital mortality rates, risk of first cardiac rehospitalization, ES-R, and MACE were not affected by age. Gender was not associated with increased long-term mortality at 3 years or the secondary endpoints.

The causative pathology for the development of ES is yet not fully understood. However, severe systolic dysfunction, chronic renal failure, and age are clinical predictors for the development of ES [17]. A meta-analysis showed a 3-fold higher risk of death in ES patients compared to VTA patients without ES [18]. However, in this meta-analysis, advanced age and gender were not associated with an increased prevalence of ES [18]. According to available research, the prognostic impact of age and gender on the long-term mortality of ICD patients who have already survived ES has never been investigated.

Age is a widely discussed risk factor for cardiovascular morbidity and mortality [8]. The incidence of VTA increases with age and is mainly attributed to structural heart diseases like ischemic or hypertensive cardiomyopathy [7, 19].

However data for elderly ES patients are very rare [8]. Most studies concentrate on conventional cardiovascular risk factors, such as arterial hypertension, diabetes mellitus, and hyperlipoproteinemia [20]. Elderly patients are frequently excluded from randomized controlled trials [8].

Studies on age are usually confronted with the argument that elderly patients, in general, are at greater risk of all-cause mortality than younger patients. In daily clinical routine, advanced age influences therapeutic decisions, as it is assumed that elderly patients are, per se, at greater risk of all-cause mortality than younger patients. In triage especially, one must be able to make the influence of advanced age objective to give the appropriate priority to chronological age. The general mortality statistics from Germany in 2015 showed that the risk of mortality per year for elderly patients (age > 60 years) was 12 times higher than that for middle-aged patients (40–60 years) (0.97% ÷ 0.08% = 12) [21]. All-cause mortality rates in the present preselected cohort of critically ill patients with ES are overall higher, but the rate for elderly patients is only 2.4 times higher than for patients under 67 (48% ÷ 20% = 2.4). The present data suggest that increasing age is associated with increased mortality in ES patients but with a weaker influence than in the general population.

In addition to chronological age, biological or vascular age might worsen prognosis in ES patients. Biological age is influenced by chronic diseases like heart failure and chronic kidney disease [6]. The present study showed that heart failure (LVEF < 35%), in addition to age ≥ 67 years, was associated with increased mortality in ES patients. Furthermore, patients 67 years old or older showed a numerically higher rate of chronic kidney disease (CKD) than patients younger than 67. Prior studies have demonstrated that severe heart failure, CKD, and age increase the risk of developing ES for ICD patients, and that elderly patients have a lower survival rate after ICD implantation (mean survival 1.5 years) when both CKD and LVEF < 35% were present [7, 17]. These findings underline that chronological age alone should not be used to estimate prognosis in ES patients, but rather that it should be evaluated in the context of a patient’s biological age.

There are several potential mechanisms in the pathogenesis of cardiac diseases and aging. The aging heart is associated with myocardial inflammation that might lead to calcium channel dysfunction, reduced cardiomyocyte density, and altered formation of collagen fibers [5, 22]. These processes have been associated with a higher risk of VTA, and they might be accelerated by VTA [23]. Laboratory experiments have investigated the effect of recurrent VTA like ES on the myocardium [24]. It has been shown that recurrent VTA are associated with increased intracellular calcium, which ultimately leads to a decreased systolic LVEF [24]. In addition, repeated ICD shocks lead to myocardial injury with consecutive myocardial inflammation and fibrosis [24]. Myocardial aging processes may encourage VTA, and VTA and ICD shocks by themselves worsen the myocardial damage of the aging heart. These kinds of myocardial damage are associated with a decreased LVEF [24] and, therefore, with poorer long-term mortality in ES patients [7].

Male gender is an established risk factor implemented in guideline-recommended risk charts that estimate future CVD development risk in an individual [1]. Prior studies have shown that steroid hormones like estrogen and progesterone are associated with lower blood pressure, vasodilatation, and lower vascular inflammation and atherosclerosis [11]. However, these differences are not found in postmenopausal women due to lower steroid hormone levels [12]. Female patients included in the present study had a mean age of 65 and were most likely postmenopausal, which might explain the findings. However, only 13 female patients were included in the present study. Therefore, a gender-dependent influence on long-term all-cause mortality in ES patients must be investigated in further studies.

In conclusion, elderly patients represent a population at the highest risk of mortality. However, in patients with ES, chronological age impacts the mortality less than in the general population. Therefore, in risk stratification the influence of chronological age of ES patients must be considered in connection with their biological age. Adequate time must be spent within a multidisciplinary team to evaluate chronic diseases, geriatric syndromes, and the optimal individual pharmacological and interventional therapy. Therapeutic goals must be determined to prevent hospitalizations and maintain patients’ quality of life [5, 21]. Male gender is an established risk factor in the development of CVD. Unfortunately, a small number of female postmenopausal patients were included in the present study. More extensive studies investigating this important risk factor are desirable. This study demonstrates the adverse prognostic impact for ES patients of age ≥ 67 years on long-term all-cause mortality at 3 years. However, the prognosis for males at 3 years was no worse than that for females.

Limitations of the study

The present observational study is based on a small sample size with retrospective data documentation. All-cause mortality was documented using an electronic hospital information system and directly contacting state resident registration offices across Germany. The mode of death could, therefore, not be verified, which is one of the main limitations of this study apart from the small sample size. Rehospitalization rates were documented only within the present institution. The management of ES has changed in recent years, which is reflected in the present study cohort. The improvements in catheter ablation for ES during the last years might have influenced survival rates in these patients, and the improvements in catheter ablation, in particular, may have affected survival rates in ES patients over time. Furthermore, ICD programming changed during the last years, mainly due to the knowledge of the MADIT-RIT study in 2012, which might have influenced the endpoints in the present study. Moreover, recent studies reported that a percutaneous stellate ganglion blockade effectively attenuates ES and might have effects on prognosis. However, stellate ganglion blocade was not performed in any of the current patients.

This paper’s low percentage of women might be underpowered for detecting differences among males and females.

Conclusions

Age ≥ 67 years was associated with increased long-term mortality in ICD patients presenting with ES. Male gender was not associated with an impaired prognosis.

Conflict of interest: None declared

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