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Effect of transthoracic shocks on left ventricular function
Resuscitation 66 (2005) 309–315
Effect of transthoracic shocks on left ventricular function夽 Kenneth M. Stein ∗ , Richard B. Devereux, Rebecca T. Hahn, Steven M. Markowitz, Suneet Mittal, Sei Iwai, Bruce B. Lerman Maurice & Corinne Greenberg Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, NY Received 1 February 2005; received in revised form 28 March 2005; accepted 28 March 2005
Abstract Although defibrillating shocks are thought to depress ventricular function transiently, the independent effects of high strength shocks (without the metabolic sequelae of pre-shock fibrillation) have not been assessed systematically in humans. Therefore, we delivered three consecutive synchronized monophasic transthoracic shocks (200, 200 and 360 J) at 60 s intervals during sinus rhythm and evaluated the effect on left ventricular chamber size and function as determined by transesophageal echocardiography in 11 patients (mean age 67 ± 8 years, 9M/2F) with depressed left ventricular function (left ventricular ejection fraction: 14–37%). The shocks did not alter hemodynamics consistently. On average, the shocks did not alter stroke volume, cardiac output, left ventricular ejection fraction or regional wall thickening (all p > 0.05 versus baseline). This effect was highly variable and 36% of patients experienced a >25% reduction in cardiac output by the final shock. There was a tendency for regional wall thickening to worsen in the best baseline sextant with an offsetting significant increase in thickening in the worst baseline sextant (p = 0.05). Thus, repetitive defibrillation strength transthoracic shocks do not impair left ventricular function consistently in patients with cardiomyopathy. However, the effect is widely variable and potentially important depression of left ventricular function does occur in some patients. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Defibrillation; Echocardiography; Left ventricle
1. Introduction Ventricular defibrillation with excessive energy levels may damage the myocardium [1–3] leading to concern that transthoracic shocks of clinically relevant magnitude might depress ventricular function. Indeed, animal studies have suggested that defibrillation strength transthoracic shocks may in fact transiently reduce left ventricular function [4,5]. Concern over potential adverse effects from excessive shock energies has influenced protocols for resuscitation from cardiac arrest and plays a role in the recommendation that the initial defibrillating ventricular shock strength should be submaximal [6–9]. This concern is not universal, however, and some authorities have argued that monophasic shocks of up
夽 A Spanish translated version of the Abstract and Keywords of this article
appears as an Appendix at 10.1016/j.resuscitation.2005.03.020. ∗ Corresponding author. E-mail address: [email protected] (K.M. Stein). 0300-9572/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2005.03.020
to 5 J/kg (approximately equal to a 360 J shock in a 70 kg subject) do not lead to myocardial damage or dysfunction [10]. Previous studies in humans have examined changes in left ventricular performance that follow successful ventricular defibrillation and demonstrated transient left ventricular dysfunction following defibrillation threshold testing at the time of defibrillator implantation [11]. However, other studies have failed to confirm any effect on left ventricular systolic function following defibrillation threshold testing [12–14]. Furthermore, evaluating left ventricular function following defibrillation does not allow one to determine whether the development of mechanical dysfunction was due to the shock itself, or whether it was simply the result of the pre-shock arrhythmia and its associated ischemic and metabolic sequelae. Thus, the independent effect of defibrillation strength transthoracic shocks on ventricular function has never been systematically assessed in humans. This is of particular significance in patients with baseline abnormalities of left ven-
310
K.M. Stein et al. / Resuscitation 66 (2005) 309–315
tole and long-axis length from apical views. Cardiac output (CO) was computed using SV and instantaneous heart rate (HR). In addition, the epicardial and endocardial borders were manually traced in systole and diastole for 3–6 beats in the short-axis view. The left ventricle was divided into 60◦ sextants and mean systolic and diastolic wall thickness and systolic wall thickening for each sextant were measured using a custom-designed software package (Digisonics Inc.). It should be noted that the echo readers were not blinded to the sequence and strength of shocks administered during the protocol. The statistical significance of changes in the hemodynamic and echocardiographic variables during the shock protocol was assessed by within subjects (“repeated measures”) ANOVA using SPSS (Version 10.1.0, SPSS Inc., Chicago, IL), using a pre-specified contrast for pairwise comparisons versus baseline. The significance of pairwise changes in relative wall thickening was assessed using the t-test. For all purposes, a p ≤ 0.05 was required to reject the null hypothesis.
tricular performance. The purpose of this study, therefore, was to determine the independent effects of defibrillation strength transthoracic shocks delivered during sinus rhythm on left ventricular chamber size and function.
2. Material and methods Patients were eligible for the study if they were: (1) >18 years old, (2) had diminished left ventricular function (left ventricular ejection fraction <40%) without significant valvular heart disease and (3) were about to undergo coronary artery bypass grafting and/or ICD implantation. Written informed consent was obtained from all subjects. The Institutional Review Board approved the investigational protocol. A radial arterial line was placed for continuous systemic hemodynamic monitoring. In addition, the first four patients underwent right heart catheterization to assess the effect of the protocol on pulmonary arterial pressures. A commercially available biplane transesophageal probe was inserted following induction of general anesthesia or deep sedation. Prior to beginning the shock protocol, a full transesophageal echocardiographic study was performed to reconfirm the absence of significant valvular heart disease. Deep gastric short-axis views of the left ventricle at the mid-papillary muscle level and midesophageal views to visualize the ventricular long-axis were then obtained at baseline. Patients then underwent three consecutive transthoracic shocks (200, 200 and 360 J monophasic waveform) at 1 min intervals [9], without moving the TEE probe. The shocks were delivered via a Hewlett-Packard Codemaster Model M1722B defibrillator, using self-adhesive pads in anterior and posterior positions. The echocardiographic images were reacquired after each shock and again 5 min after the final shock. Off-line echocardiographic image analysis was performed using a Digisonics CardioRevue Center. Left ventricular volumes (left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV) and stroke volume (SV)) were calculated by the area–length method [15] using the short-axis areas determined in systole and dias-
3. Results Eleven subjects were enrolled with a mean age of 67 ± 8 years. There were nine men and two women. The mean left ventricular ejection fraction was 25 ± 7% (range: 14–37%). Ten subjects had significant coronary artery disease, while the other had an idiopathic dilated cardiomyopathy. The shock protocol had no consistent effect on systemic hemodynamics (Fig. 1) or on pulmonary hemodynamics in the subset of patients monitored with right heart catheterization (Fig. 2). There were nonsignificant trends toward reductions of left ventricular ejection fraction (Fig. 3A: baseline: 25%, shock 1: 24%, shock 2: 23% and shock 3: 23%, p = 0.18), stroke volume (Fig. 3B: baseline: 64 ml, shock 1: 57 ml, shock 2: 59 ml and shock 3: 54 ml, p = 0.18) and cardiac output (Fig. 3B: baseline: 4.3 l, shock 1: 4.0 l, shock 2: 3.8 l and shock 3: 3.6 l, p = 0.35) following the shocks. However, the effects on left ventricular systolic performance were highly variable (Table 1). No patient experienced
Table 1 Individual effects of transthoracic shocks on echocardiographically-derived measures of left ventricular ejection fraction (EF) and cardiac output Patients
1 2 3 4 5 6 7 8 9 10 11
EF (%)
Cardiac output (l/min)
Baseline
200 J-1
200 J-2
360 J
Baseline
200 J-1
200 J-2
360 J
14 16 30 26 26 24 22 28 16 32 37
11 15 27 23 20 23 18 ND 16 47 38
13 19 27 17 25 21 21 ND 18 ND 40
10 7 30 20 32 8 16 33 14 43 39
5.1 3.4 3.2 5.5 4.2 3.9 7.6 4.3 2.8 4.0 3.2
3.9 3.6 2.7 5.2 3.0 3.1 4.0 ND 4.5 6.1 3.6
4.2 5.3 2.4 3.6 3.9 3.1 4.2 ND 3.9 ND 3.9
4.3 1.3 2.8 4.1 4.9 1.0 3.7 2.9 4.4 5.9 4.2
ND, not determined due to inadequate imaging.
K.M. Stein et al. / Resuscitation 66 (2005) 309–315
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Fig. 1. Systemic hemodynamics (A: heart rate, B: systolic blood pressure (SBP), C: diastolic blood pressure (DBP) and D: double product (heart rate multiplied by systolic blood pressure)) in all 11 patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J-2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
Fig. 2. Pulmonary hemodynamics (A: heart rate, B: pulmonary arterial systolic blood pressure, C: pulmonary arterial diastolic blood pressure and D: pulmonary arterial wedge pressure) in four patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J-2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
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Fig. 3. Echocardiographically-derived measures of left ventricular function (A: stroke volume, B: left ventricular ejection fraction and C: cardiac output) in all 11 patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J-2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
a clinically significant (>25%) reduction in cardiac output after the first shock and only one patient had a clinically significant reduction in cardiac output after the second shock. However, after the final shock 4/11 patients (36%) had a
>25% reduction in cardiac output. In one patient, left ventricular ejection fraction fell from 24 to 8% and cardiac output fell from 3.9 to 1.0 l/min by the final shock (Fig. 4). In another patient, left ventricular ejection fraction fell from 16 to 7%
Fig. 4. Digitized epicardial and endocardial shells at end-diastole and end-systole during baseline imaging and immediately following the transthoracic shock protocol (patient #6). Left ventricular ejection fraction fell from 24 to 8% and cardiac output fell from 3.9 to 1.0 l/min.
K.M. Stein et al. / Resuscitation 66 (2005) 309–315
Fig. 5. Regional wall thickening in the best vs. worst baseline segment in all 11 patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J–2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
and cardiac output fell from 3.4 to 1.3 l/min. In these patients and in all other patients, the values returned to baseline within 5 min of the final shock. No patient developed pulmonary edema following the shocks. There was no consistent overall effect on regional LV systolic function as assessed by systolic thickening in all 66 (6 regions in each of 11 patients) sextants (baseline regional wall thickening: 0.11 ± 0.01 mm, shock 1: 0.12 ± 0.02 mm, shock 2: 0.11 ± 0.02 mm and shock 3: 0.11 ± 0.02 mm, p = 0.47). Detailed analysis revealed diminished thickening in the best baseline sextant but a corresponding tendency to improve in the worst baseline sextant (Fig. 5).
4. Discussion Defibrillation strength transthoracic shocks do not consistently impair left ventricular systolic performance or systemic hemodynamics in human subjects with compromised LV function at baseline. However, the effect is widely variable and, in approximately one-third of patients, clinically significant depression of left ventricular function may occur after a series of escalating shocks. This effect was solely attributable to the shocks, since the shocks were delivered synchronously in sinus rhythm without induction of any arrhythmia. Thus, the use of the lowest effective defibrillating energy dose may reduce the risk of significant, albeit transient, ventricular dysfunction. Animal experiments have clearly demonstrated that transthoracic defibrillating shocks of sufficient magnitude may result in myocardial dysfunction and necrosis [1–3]. In myocardial cell tissue culture, shock strength external fields lead to ultrastructural injury and to abnormalities of contractile function [16]. Likewise, in normal dogs (weighing ∼10–30 kg) repetitive 400 J transthoracic shocks cause myocardial injury [1,17], and direct epicardial shocks lead to a diminution in cardiac output [5]. In a porcine model,
313
transthoracic defibrillation strength shocks (biphasic) delivered during sinus rhythm transiently depressed left ventricular contractility, but this effect disappears within 30 s [4]. Animal experiments have shown that the magnitude of postresuscitation myocardial dysfunction varies inversely with the magnitude of the defibrillating shock, implying an independent adverse effect from the shock itself (at least at higher energies) [18]. However, other authors have failed to observe alterations in left ventricular ejection fraction after administering high-energy shocks in sinus rhythm [19]. In one canine study, depressed left ventricular contractility was observed after direct epicardial shocks, but was not present even after delivering multiple transthoracic shocks of up to 460 J [20]. In humans, reversible myocardial dysfunction has long been appreciated in cardiac arrest survivors (lasting for up to 2 weeks following the event) and has been attributed to the defibrillating shocks themselves as well as to the effects of ischemia [21]. Stoddard et al. reported transient alterations in both systolic and diastolic function following defibrillation of ventricular tachyarrhythmias induced during electrophysiologic studies [22]. Defibrillation threshold testing at the time of defibrillator implantation may be associated with subtle elevations in cardiac enzymes [23] and transient depression of cardiac output has been observed following defibrillation threshold testing in patients with severely depressed left ventricular function at baseline (left ventricular ejection fraction below 30%) [11]. However, the data are nonuniform and other investigators have found repeated defibrillation threshold testing to have no effect on echocardiographic fractional shortening [12,14], ejection fraction [13,24] or cardiac output [25]. These previous human studies, examining left ventricular dysfunction following ventricular defibrillation, do not (by design) permit an independent assessment of any effect of the shock(s) on the myocardium as opposed to the intrinsic effects of the arrhythmia and consequent pre-shock ischemia. Even brief periods of ventricular fibrillation lead to the metabolic sequelae of hypoperfusion [26]. In addition to ischemic injury, it is also possible that post-resuscitation left ventricular dysfunction may also be due to reperfusion injury [27,28]. In the present study we found no statistically significant effect of the transthoracic shocks delivered in sinus rhythm on mean values for pulmonary or systemic hemodynamic variables or on echocardiographically-derived indices of left ventricular chamber size or function in patients with baseline left ventricular dysfunction. There was a minimal risk of shock-induced depression of left ventricular function following a single 200 J transthoracic shock. However, following three consecutive shocks (using clinically relevant energy levels: 200, 200 and 360 J), a wide range of effects was observed and changes in cardiac output large enough to be clinically significant were observed in 36% of patients. Due to the nonrandomized sequence of shocks, it is unclear whether this reflects an effect of delivering repetitive shocks or whether it was due to the higher strength of the third shock. In all patients the values returned to baseline within 5 min.
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The relative brevity of effect suggests that the longer duration of left ventricular dysfunction observed in clinical studies of resuscitation reflect effects of the underlying arrhythmia and its hemodynamic sequelae. To examine whether the local effects of the shocks varied depending on regional myocardial function, we contrasted the effects of the shock on regional wall thickening in the worst performing sextant of myocardium at baseline with the effects on the best baseline sextant. We observed a tendency for regional wall thickening to deteriorate in the best baseline sextant. However, given the simultaneous observation of an offsetting improvement in regional function in the worst baseline segment it is most likely that this represents the phenomenon of “regression to the mean”. Several mechanisms have been proposed to account for shock induced myocardial dysfunction. One potential mechanism is electroporation of the myocardial cell membrane [29]. Another is the possibility that the voltage gradient may directly generate free radicals [30], leading to sarcolemmal and mitochondrial [31] damage. Conformational damage to ion pumps/channels, barotrauma and hyperthermia have also been proposed as possible mechanisms for defibrillationmediated myocardial dysfunction [29]. It is acknowledged that the sample size in the present study was relatively small, which was related to difficulties recruiting patients for the protocol. Nevertheless, it should be emphasized that these data are unique in human subjects. The present study analyzed the effects of a damped sine-wave monophasic defibrillating waveform and the results cannot necessarily be extrapolated to biphasic ventricular defibrillation [32,33]. Examination of the effect of biphasic shocks is clearly warranted, but it should be emphasized that the majority of external defibrillators in current use are still monophasic devices. Additionally, although the study design sought to isolate the effect of the shock on left ventricular function from the effect of ventricular fibrillation and consequent hypoperfusion, it does not eliminate the possibility of a synergistic interaction (e.g. the possibility that acute ischemia potentiates shock-induced ventricular dysfunction) [34]. In this context, it should be noted that 10/11 patients in the present study had significant ischemic heart disease. Finally, although the degree of interindividual variability in the response to the shocks was striking, the present data do not offer any specific reasons for this variability.
5. Conclusions Defibrillation strength transthoracic shocks do not consistently affect ventricular performance even in human subjects with baseline left ventricular dysfunction. Nevertheless, potentially important reductions in ejection fraction and cardiac output may occur following repetitive shocks. Thus, in patients with severe left ventricular dysfunction, attempting to defibrillate using the lowest effective energy dose remains a prudent strategy.
Acknowledgements This work was supported in part by grants from the National Institutes of Health (ROI HL-56139), the Rosenfeld Heart Foundation, the Michael Wolk Foundation, the Raymond and Beverly Sackler Foundation and New York Cardiology Associates.
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K.M. Stein et al. / Resuscitation 66 (2005) 309–315 [16] Jones JL, Proskauer CC, Paull WK, Lepeschkin E, Jones RE. Ultrastructural injury to chick myocardial cells in vitro following “electric countershock”. Circ Res 1980;46:387–94. [17] DiCola VC, Freedman GS, Downing SE, Zaret BL. Myocardial uptake of technietium-99m stannous pyrophosphate following direct current transthoracic countershock. Circulation 1976;54:980–6. [18] Xie J, Weil MH, Sun S, et al. High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction. Circulation 1997;96:683–8. [19] Kern KB, Hilwig RW, Rhee KH, Berg RA. Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning. J Am Coll Cardiol 1996;28:232–40. [20] Kerber RE, Martins JB, Gascho JA, Marcus ML, Grayzel J. Effect of direct-current countershocks on regional myocardial contractility and perfusion: experimental studies. Circulation 1981;63:323– 32. [21] Deantonio HJ, Kaul S, Lerman BB. Reversible myocardial depression in survivors of cardiac arrest. PACE 1990;13:982–5. [22] Stoddard MF, Labovitz AJ, Stevens LL, Buckingham TA, Redd RR, Kennedy HL. Effects of electrophysiologic studies resulting in electrical countershock or burst pacing on left ventricular systolic and diastolic function. Am Heart J 1988;116:364–70. [23] Hurst TM, Hinrichs M, Breidenbach C, Katz N, Waldecker B. Detection of myocardial injury during transvenous implantation of automatic cardioverter-defibrillators. J Am Coll Cardiol 1999;34:402– 8. [24] Antunes ML, Spotnitz HM, Livelli FD, Steinberg JS, Bigger JT. Effect of electrophysiological testing on ejection fraction during; cardioverter/defibrillator implantation. Ann Thorac Surg 1988;45:315– 8.
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[25] Meyer J, Mollhoff T, Seifert T, et al. Cardiac output is not affected during intraoperative testing of the automatic implaniable cardioverters defibrillator. J Cardiovasc Electrophysiol 1996;7:211–6. [26] Lerman BB, Engelstein ED. Metabolic determinants of defibrillation: role of adenosine. Circulation 1995;91:838–44. [27] Tang W, Weil MH, Sun S, Gazmuri RJ, Bisera J. Progressive myocardial dysfunction after cardiac resuscitation. Crit Care Med 1993;21:1046–50. [28] Gazmuri RJ, Weil MH, Bisera J, Tang W, Fukui M, McKee D. Myocardial dysfunction after successful resuscitation from cardiac arrest. Crit Care Med 1996;24:992–1000. [29] Tang L. Detrimental effects of electrical fields on cardiac muscle. Proc IEEE 1996;84:366–78. [30] Caterine MR, Spencer KT, Pagan-Carlo LA, Smith RS, Buettner GR, Kerber RE. Direct current shocks to the heart generate free radicals: an electron paramagnetic resonance study. J Am Coll Cardiol 1996;28:1598–609. [31] Trouton TC, Allen JD, Yong LK, Rooney JJ, Adgey AAJ. Metabolic changes and mitochondrial dysfunction early following transthoracic countershock in dogs. PACE 1989;12:1827–34. [32] Mittal S, Ayati S, Stein KM, et al. Comparison of a novel rectilinear biphasic waveform with a damped sine wave monophase waveform for transthoracic ventricular defibrillation. J Am Coll Cardiol 1999;34:1595–601. [33] Tang W, Weil MH, Sun S, et al. The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial dysfunction. J Am Coll Cardiol 1999;34:815–22. [34] Yamaguchi H, Weil M, Tang W, Kamohara T, Jin X, Bisera J. Myocardial dysfunction after electrical defibrillation. Resuscitation 2002;54:289–96.
Effect of transthoracic shocks on left ventricular function夽 Kenneth M. Stein ∗ , Richard B. Devereux, Rebecca T. Hahn, Steven M. Markowitz, Suneet Mittal, Sei Iwai, Bruce B. Lerman Maurice & Corinne Greenberg Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, NY Received 1 February 2005; received in revised form 28 March 2005; accepted 28 March 2005
Abstract Although defibrillating shocks are thought to depress ventricular function transiently, the independent effects of high strength shocks (without the metabolic sequelae of pre-shock fibrillation) have not been assessed systematically in humans. Therefore, we delivered three consecutive synchronized monophasic transthoracic shocks (200, 200 and 360 J) at 60 s intervals during sinus rhythm and evaluated the effect on left ventricular chamber size and function as determined by transesophageal echocardiography in 11 patients (mean age 67 ± 8 years, 9M/2F) with depressed left ventricular function (left ventricular ejection fraction: 14–37%). The shocks did not alter hemodynamics consistently. On average, the shocks did not alter stroke volume, cardiac output, left ventricular ejection fraction or regional wall thickening (all p > 0.05 versus baseline). This effect was highly variable and 36% of patients experienced a >25% reduction in cardiac output by the final shock. There was a tendency for regional wall thickening to worsen in the best baseline sextant with an offsetting significant increase in thickening in the worst baseline sextant (p = 0.05). Thus, repetitive defibrillation strength transthoracic shocks do not impair left ventricular function consistently in patients with cardiomyopathy. However, the effect is widely variable and potentially important depression of left ventricular function does occur in some patients. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Defibrillation; Echocardiography; Left ventricle
1. Introduction Ventricular defibrillation with excessive energy levels may damage the myocardium [1–3] leading to concern that transthoracic shocks of clinically relevant magnitude might depress ventricular function. Indeed, animal studies have suggested that defibrillation strength transthoracic shocks may in fact transiently reduce left ventricular function [4,5]. Concern over potential adverse effects from excessive shock energies has influenced protocols for resuscitation from cardiac arrest and plays a role in the recommendation that the initial defibrillating ventricular shock strength should be submaximal [6–9]. This concern is not universal, however, and some authorities have argued that monophasic shocks of up
夽 A Spanish translated version of the Abstract and Keywords of this article
appears as an Appendix at 10.1016/j.resuscitation.2005.03.020. ∗ Corresponding author. E-mail address: [email protected] (K.M. Stein). 0300-9572/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2005.03.020
to 5 J/kg (approximately equal to a 360 J shock in a 70 kg subject) do not lead to myocardial damage or dysfunction [10]. Previous studies in humans have examined changes in left ventricular performance that follow successful ventricular defibrillation and demonstrated transient left ventricular dysfunction following defibrillation threshold testing at the time of defibrillator implantation [11]. However, other studies have failed to confirm any effect on left ventricular systolic function following defibrillation threshold testing [12–14]. Furthermore, evaluating left ventricular function following defibrillation does not allow one to determine whether the development of mechanical dysfunction was due to the shock itself, or whether it was simply the result of the pre-shock arrhythmia and its associated ischemic and metabolic sequelae. Thus, the independent effect of defibrillation strength transthoracic shocks on ventricular function has never been systematically assessed in humans. This is of particular significance in patients with baseline abnormalities of left ven-
310
K.M. Stein et al. / Resuscitation 66 (2005) 309–315
tole and long-axis length from apical views. Cardiac output (CO) was computed using SV and instantaneous heart rate (HR). In addition, the epicardial and endocardial borders were manually traced in systole and diastole for 3–6 beats in the short-axis view. The left ventricle was divided into 60◦ sextants and mean systolic and diastolic wall thickness and systolic wall thickening for each sextant were measured using a custom-designed software package (Digisonics Inc.). It should be noted that the echo readers were not blinded to the sequence and strength of shocks administered during the protocol. The statistical significance of changes in the hemodynamic and echocardiographic variables during the shock protocol was assessed by within subjects (“repeated measures”) ANOVA using SPSS (Version 10.1.0, SPSS Inc., Chicago, IL), using a pre-specified contrast for pairwise comparisons versus baseline. The significance of pairwise changes in relative wall thickening was assessed using the t-test. For all purposes, a p ≤ 0.05 was required to reject the null hypothesis.
tricular performance. The purpose of this study, therefore, was to determine the independent effects of defibrillation strength transthoracic shocks delivered during sinus rhythm on left ventricular chamber size and function.
2. Material and methods Patients were eligible for the study if they were: (1) >18 years old, (2) had diminished left ventricular function (left ventricular ejection fraction <40%) without significant valvular heart disease and (3) were about to undergo coronary artery bypass grafting and/or ICD implantation. Written informed consent was obtained from all subjects. The Institutional Review Board approved the investigational protocol. A radial arterial line was placed for continuous systemic hemodynamic monitoring. In addition, the first four patients underwent right heart catheterization to assess the effect of the protocol on pulmonary arterial pressures. A commercially available biplane transesophageal probe was inserted following induction of general anesthesia or deep sedation. Prior to beginning the shock protocol, a full transesophageal echocardiographic study was performed to reconfirm the absence of significant valvular heart disease. Deep gastric short-axis views of the left ventricle at the mid-papillary muscle level and midesophageal views to visualize the ventricular long-axis were then obtained at baseline. Patients then underwent three consecutive transthoracic shocks (200, 200 and 360 J monophasic waveform) at 1 min intervals [9], without moving the TEE probe. The shocks were delivered via a Hewlett-Packard Codemaster Model M1722B defibrillator, using self-adhesive pads in anterior and posterior positions. The echocardiographic images were reacquired after each shock and again 5 min after the final shock. Off-line echocardiographic image analysis was performed using a Digisonics CardioRevue Center. Left ventricular volumes (left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV) and stroke volume (SV)) were calculated by the area–length method [15] using the short-axis areas determined in systole and dias-
3. Results Eleven subjects were enrolled with a mean age of 67 ± 8 years. There were nine men and two women. The mean left ventricular ejection fraction was 25 ± 7% (range: 14–37%). Ten subjects had significant coronary artery disease, while the other had an idiopathic dilated cardiomyopathy. The shock protocol had no consistent effect on systemic hemodynamics (Fig. 1) or on pulmonary hemodynamics in the subset of patients monitored with right heart catheterization (Fig. 2). There were nonsignificant trends toward reductions of left ventricular ejection fraction (Fig. 3A: baseline: 25%, shock 1: 24%, shock 2: 23% and shock 3: 23%, p = 0.18), stroke volume (Fig. 3B: baseline: 64 ml, shock 1: 57 ml, shock 2: 59 ml and shock 3: 54 ml, p = 0.18) and cardiac output (Fig. 3B: baseline: 4.3 l, shock 1: 4.0 l, shock 2: 3.8 l and shock 3: 3.6 l, p = 0.35) following the shocks. However, the effects on left ventricular systolic performance were highly variable (Table 1). No patient experienced
Table 1 Individual effects of transthoracic shocks on echocardiographically-derived measures of left ventricular ejection fraction (EF) and cardiac output Patients
1 2 3 4 5 6 7 8 9 10 11
EF (%)
Cardiac output (l/min)
Baseline
200 J-1
200 J-2
360 J
Baseline
200 J-1
200 J-2
360 J
14 16 30 26 26 24 22 28 16 32 37
11 15 27 23 20 23 18 ND 16 47 38
13 19 27 17 25 21 21 ND 18 ND 40
10 7 30 20 32 8 16 33 14 43 39
5.1 3.4 3.2 5.5 4.2 3.9 7.6 4.3 2.8 4.0 3.2
3.9 3.6 2.7 5.2 3.0 3.1 4.0 ND 4.5 6.1 3.6
4.2 5.3 2.4 3.6 3.9 3.1 4.2 ND 3.9 ND 3.9
4.3 1.3 2.8 4.1 4.9 1.0 3.7 2.9 4.4 5.9 4.2
ND, not determined due to inadequate imaging.
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Fig. 1. Systemic hemodynamics (A: heart rate, B: systolic blood pressure (SBP), C: diastolic blood pressure (DBP) and D: double product (heart rate multiplied by systolic blood pressure)) in all 11 patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J-2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
Fig. 2. Pulmonary hemodynamics (A: heart rate, B: pulmonary arterial systolic blood pressure, C: pulmonary arterial diastolic blood pressure and D: pulmonary arterial wedge pressure) in four patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J-2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
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Fig. 3. Echocardiographically-derived measures of left ventricular function (A: stroke volume, B: left ventricular ejection fraction and C: cardiac output) in all 11 patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J-2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
a clinically significant (>25%) reduction in cardiac output after the first shock and only one patient had a clinically significant reduction in cardiac output after the second shock. However, after the final shock 4/11 patients (36%) had a
>25% reduction in cardiac output. In one patient, left ventricular ejection fraction fell from 24 to 8% and cardiac output fell from 3.9 to 1.0 l/min by the final shock (Fig. 4). In another patient, left ventricular ejection fraction fell from 16 to 7%
Fig. 4. Digitized epicardial and endocardial shells at end-diastole and end-systole during baseline imaging and immediately following the transthoracic shock protocol (patient #6). Left ventricular ejection fraction fell from 24 to 8% and cardiac output fell from 3.9 to 1.0 l/min.
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Fig. 5. Regional wall thickening in the best vs. worst baseline segment in all 11 patients at baseline and following synchronous transthoracic shocks (200 J-1, 200 J–2 and 360 J) during sinus rhythm. Results are shown as mean ± standard error.
and cardiac output fell from 3.4 to 1.3 l/min. In these patients and in all other patients, the values returned to baseline within 5 min of the final shock. No patient developed pulmonary edema following the shocks. There was no consistent overall effect on regional LV systolic function as assessed by systolic thickening in all 66 (6 regions in each of 11 patients) sextants (baseline regional wall thickening: 0.11 ± 0.01 mm, shock 1: 0.12 ± 0.02 mm, shock 2: 0.11 ± 0.02 mm and shock 3: 0.11 ± 0.02 mm, p = 0.47). Detailed analysis revealed diminished thickening in the best baseline sextant but a corresponding tendency to improve in the worst baseline sextant (Fig. 5).
4. Discussion Defibrillation strength transthoracic shocks do not consistently impair left ventricular systolic performance or systemic hemodynamics in human subjects with compromised LV function at baseline. However, the effect is widely variable and, in approximately one-third of patients, clinically significant depression of left ventricular function may occur after a series of escalating shocks. This effect was solely attributable to the shocks, since the shocks were delivered synchronously in sinus rhythm without induction of any arrhythmia. Thus, the use of the lowest effective defibrillating energy dose may reduce the risk of significant, albeit transient, ventricular dysfunction. Animal experiments have clearly demonstrated that transthoracic defibrillating shocks of sufficient magnitude may result in myocardial dysfunction and necrosis [1–3]. In myocardial cell tissue culture, shock strength external fields lead to ultrastructural injury and to abnormalities of contractile function [16]. Likewise, in normal dogs (weighing ∼10–30 kg) repetitive 400 J transthoracic shocks cause myocardial injury [1,17], and direct epicardial shocks lead to a diminution in cardiac output [5]. In a porcine model,
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transthoracic defibrillation strength shocks (biphasic) delivered during sinus rhythm transiently depressed left ventricular contractility, but this effect disappears within 30 s [4]. Animal experiments have shown that the magnitude of postresuscitation myocardial dysfunction varies inversely with the magnitude of the defibrillating shock, implying an independent adverse effect from the shock itself (at least at higher energies) [18]. However, other authors have failed to observe alterations in left ventricular ejection fraction after administering high-energy shocks in sinus rhythm [19]. In one canine study, depressed left ventricular contractility was observed after direct epicardial shocks, but was not present even after delivering multiple transthoracic shocks of up to 460 J [20]. In humans, reversible myocardial dysfunction has long been appreciated in cardiac arrest survivors (lasting for up to 2 weeks following the event) and has been attributed to the defibrillating shocks themselves as well as to the effects of ischemia [21]. Stoddard et al. reported transient alterations in both systolic and diastolic function following defibrillation of ventricular tachyarrhythmias induced during electrophysiologic studies [22]. Defibrillation threshold testing at the time of defibrillator implantation may be associated with subtle elevations in cardiac enzymes [23] and transient depression of cardiac output has been observed following defibrillation threshold testing in patients with severely depressed left ventricular function at baseline (left ventricular ejection fraction below 30%) [11]. However, the data are nonuniform and other investigators have found repeated defibrillation threshold testing to have no effect on echocardiographic fractional shortening [12,14], ejection fraction [13,24] or cardiac output [25]. These previous human studies, examining left ventricular dysfunction following ventricular defibrillation, do not (by design) permit an independent assessment of any effect of the shock(s) on the myocardium as opposed to the intrinsic effects of the arrhythmia and consequent pre-shock ischemia. Even brief periods of ventricular fibrillation lead to the metabolic sequelae of hypoperfusion [26]. In addition to ischemic injury, it is also possible that post-resuscitation left ventricular dysfunction may also be due to reperfusion injury [27,28]. In the present study we found no statistically significant effect of the transthoracic shocks delivered in sinus rhythm on mean values for pulmonary or systemic hemodynamic variables or on echocardiographically-derived indices of left ventricular chamber size or function in patients with baseline left ventricular dysfunction. There was a minimal risk of shock-induced depression of left ventricular function following a single 200 J transthoracic shock. However, following three consecutive shocks (using clinically relevant energy levels: 200, 200 and 360 J), a wide range of effects was observed and changes in cardiac output large enough to be clinically significant were observed in 36% of patients. Due to the nonrandomized sequence of shocks, it is unclear whether this reflects an effect of delivering repetitive shocks or whether it was due to the higher strength of the third shock. In all patients the values returned to baseline within 5 min.
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The relative brevity of effect suggests that the longer duration of left ventricular dysfunction observed in clinical studies of resuscitation reflect effects of the underlying arrhythmia and its hemodynamic sequelae. To examine whether the local effects of the shocks varied depending on regional myocardial function, we contrasted the effects of the shock on regional wall thickening in the worst performing sextant of myocardium at baseline with the effects on the best baseline sextant. We observed a tendency for regional wall thickening to deteriorate in the best baseline sextant. However, given the simultaneous observation of an offsetting improvement in regional function in the worst baseline segment it is most likely that this represents the phenomenon of “regression to the mean”. Several mechanisms have been proposed to account for shock induced myocardial dysfunction. One potential mechanism is electroporation of the myocardial cell membrane [29]. Another is the possibility that the voltage gradient may directly generate free radicals [30], leading to sarcolemmal and mitochondrial [31] damage. Conformational damage to ion pumps/channels, barotrauma and hyperthermia have also been proposed as possible mechanisms for defibrillationmediated myocardial dysfunction [29]. It is acknowledged that the sample size in the present study was relatively small, which was related to difficulties recruiting patients for the protocol. Nevertheless, it should be emphasized that these data are unique in human subjects. The present study analyzed the effects of a damped sine-wave monophasic defibrillating waveform and the results cannot necessarily be extrapolated to biphasic ventricular defibrillation [32,33]. Examination of the effect of biphasic shocks is clearly warranted, but it should be emphasized that the majority of external defibrillators in current use are still monophasic devices. Additionally, although the study design sought to isolate the effect of the shock on left ventricular function from the effect of ventricular fibrillation and consequent hypoperfusion, it does not eliminate the possibility of a synergistic interaction (e.g. the possibility that acute ischemia potentiates shock-induced ventricular dysfunction) [34]. In this context, it should be noted that 10/11 patients in the present study had significant ischemic heart disease. Finally, although the degree of interindividual variability in the response to the shocks was striking, the present data do not offer any specific reasons for this variability.
5. Conclusions Defibrillation strength transthoracic shocks do not consistently affect ventricular performance even in human subjects with baseline left ventricular dysfunction. Nevertheless, potentially important reductions in ejection fraction and cardiac output may occur following repetitive shocks. Thus, in patients with severe left ventricular dysfunction, attempting to defibrillate using the lowest effective energy dose remains a prudent strategy.
Acknowledgements This work was supported in part by grants from the National Institutes of Health (ROI HL-56139), the Rosenfeld Heart Foundation, the Michael Wolk Foundation, the Raymond and Beverly Sackler Foundation and New York Cardiology Associates.
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