- Email: [email protected]
Stress-induced cardiomyopathy in the critically ill — Why inotropes fail to improve outcome
Letters to the Editor
4489
Stress-induced cardiomyopathy in the critically ill — Why inotropes fail to improve outcome Bjorn Redfors a,b,⁎, Yangzhen Shao a, Elmir Omerovic a,b a b
Wallenberg Laboratory at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
a r t i c l e
i n f o
Article history: Received 20 May 2013 Accepted 30 June 2013 Available online 18 July 2013 Keywords: Stress-induced cardiomyopathy Inotropes Catecholamines Intensive care unit
Cardiac dysfunction is common in ICU patients and is a poor prognostic factor [1,2]. Acute myocardial infarction (AMI) is commonly diagnosed in ICU patients and cardiospecific proteins are detected in up to 47% of these patients. An AMI diagnosis is often based only on detection of cardiospecific proteins in plasma and/or ECG and echocardiographic findings. Angiographic evidence is rarely present [2]. Furthermore, reported plasma troponin levels are often mildly to moderately elevated, a laboratory finding that is consistent not only with a small or moderately sized AMI but also with stress-induced cardiomyopathy (SIC). It is thus possible that many or perhaps most cases of myocardial infarction diagnosed in the ICU may in fact be SIC. SIC was first described in 1990 but is now an increasingly recognized acute cardiac syndrome and an important differential diagnosis in patients presenting with chest pain [3]. SIC is characterized by severe regional myocardial hypokinesia or akinesia, often but not always involving apical segments, in the absence of an explanatory coronary lesion [4]. Although the pathomechanisms behind SIC is believed to differ substantially from that of AMI the two conditions appear clinically similar and cannot, as yet, be differentiated by non-invasive modalities [5]. However, plasma troponin levels are typically mildly to moderately elevated in SIC and extreme values are rare. SIC is typically preceded by an emotional or somatic stressor and although the pathophysiology of SIC is poorly understood, there exist strong evidence for an important role of catecholamine overstimulation [5]. Among the evidence indicating catecholamines in the pathogenesis of SIC are the observations that plasma levels of epinephrine and norepinephrine are severely elevated in SIC patients, also compared to AMI patients, and several reports where iatrogenously administered beta-adrenergic agonists have triggered SIC or worsened the patients' condition [5,6]. Furthermore, we have shown that i.p. administration of isoprenaline, a nonselective β-adrenoreceptor agonist, induces SIC-like left ventricular apical akinesia in rats [7]. We believe that there is reason to believe that SIC may be particularly prevalent among patients admitted because of severe non-cardiac disease, conditions associated with internal somatic stress and a strong adrenergic drive. A recent report showed that N20% of patients admitted to an intensive care unit (ICU) displayed SIC-like left ventricular apical ballooning. Development of SIC-like cardiac dysfunction was particularly likely in sepsis, a condition associated with a profound endogenous stress response [1].
⁎ Corresponding author at: Bruna stråket 16, SE 413 45 Gothenburg, Sweden. Tel.: + 46 31 343 7560; fax: + 46 31 823762. E-mail address: [email protected] (B. Redfors).
Considering the liberal use of inotropic support in ICU patients, including catecholamine, detection of SIC patients in this setting may be of particular importance and may merit re-evaluation of treatment strategies [6,8]. Cardiac output is often inadequate in ICU patients despite optimization of filling pressures and afterload. These patients therefore require additional support to maintain adequate tissue perfusion. Typical regimens include positive inotropes and/or vasopressor substances, many of which are catecholamines. We believe that further stimulation of adrenergic signaling pathways may exacerbate cardiac dysfunction in some patients and may lead to paradoxical deterioration of these patients condition (Fig. 1). In patients suffering from severe heart failure inotropic support by the β-adrenoreceptor agonist dobutamine was associated with a near statistically significantly increased mortality compared to placebo [8]. We believe that suspicion of stress-induced cardiac dysfunction should deter the anesthesiologist towards switching to non-catecholamine vasopressors. Similarly, non-catecholamine vasopressors may also be preferable in these patients. We propose that many so-called AMIs detected in the ICU may in fact be SIC and in many cases these SICs may have been caused or exacerbated by iatrogenously administered inotropic agents, especially β-adrenoreceptor agonist. Non-catecholamine inotropes and/or vasopressors or mechanical assist may be preferable in patients at risk of developing SIC. Until SIC is better understood and these patients can be identified we argue for judicious use of catecholamine inotropes and liberal use of mechanical assist, particularly in patients displaying signs of cardiac dysfunction or injury.
Fig. 1. Vicious cycle of inotropic support in stress-induced cardiomyopathy. Catecholamine vasopressor and inotropes administered to improve cardiac functional impairment and hypotension may instead further worsen cardiac function. This in turn aggravates hypotension and may lead to a decision to increase catecholamine doses.
4490
Letters to the Editor
References [1] Park JH, Kang SJ, Song JK, et al. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest 2005;128:296–302. [2] Lim W, Qushmaq I, Cook DJ, et al. Elevated troponin and myocardial infarction in the intensive care unit: a prospective study. Crit Care 2005;9:R636–44. [3] Shao Y, Redfors B, Lyon AR, Rosengren A, Swedberg K, Omerovic E. Trends in publications on stress-induced cardiomyopathy. Int J Cardiol 2012;157:435–6. [4] Schultz T, Shao Y, Redfors B, et al. Stress-induced cardiomyopathy in Sweden: evidence for different ethnic predisposition and altered cardio-circulatory status. Cardiology 2012;122:180–6.
[5] Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539–48. [6] Redfors B, Shao Y, Omerovic E. Stress-induced cardiomyopathy in a patient with chronic spinal cord transection at the level of C5: endocrinologically mediated catecholamine toxicity. Int J Cardiol 2012;159:e61–2. [7] Shao Y, Redfors B, Scharin Tang M, et al. Novel rat model reveals important roles of betaadrenoreceptors in stress-induced cardiomyopathy. Int J Cardiol 2013;168(3):1943–50. [8] Tacon CL, McCaffrey J, Delaney A. Dobutamine for patients with severe heart failure: a systematic review and meta-analysis of randomised controlled trials. Intensive Care Med 2012;38:359–67.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.06.128
First-in-human description of everolimus-eluting bioabsorbable vascular scaffold implantation for the treatment of drug-eluting stent failure: Insights from optical coherence tomography Carmelo Grasso a, Guilherme F. Attizzani a,⁎, Martina Patané a, Yohei Ohno a, Davide Capodanno a,b, Corrado Tamburino a,b a b
Division of Cardiology, Ferrarotto Hospital, University of Catania, Italy Excellence Through Newest Advances (ETNA) Foundation, Catania, Italy
a r t i c l e
i n f o
Article history: Received 21 May 2013 Accepted 30 June 2013 Available online 24 July 2013 Keywords: Bioresorbable vascular scaffold In-stent restenosis Optical coherence tomography
Drug-eluting stents (DES) markedly reduce new episodes of revascularization compared with bare-metal stents; nevertheless, the prevalence of DES in-stent restenosis (ISR) is not insignificant as a large population is treated with these devices worldwide [1]. In addition, concerns regarding long-term safety of metallic DES [2] stimulated investigators to seek for improvement of this therapy. Everolimuseluting bioabsorbable vascular scaffolds (BVS, Abbott Vascular, Santa Clara, CA, USA) emerged as an interesting alternative, as they enable vessel scaffolding in short-term and anti-restenotic drug delivery, while avoiding long-term limitations of metallic DES (i.e., prolonged metal exposure to coronary circulation in case of delayed healing). Indeed, BVS demonstrated promising results in the treatment of de novo coronary lesions [3]. Meanwhile, optical coherence tomography (OCT) imaging was proved the most suitable intravascular imaging modality to assess BVS-vessel interactions in vivo [4]. Nevertheless, the use of BVS in the treatment of ISR has never been documented. We report for the first time, baseline and 9-month follow-up OCT assessments of BVS implantation for the treatment of DES failure (i.e., recurrent DES ISR and neoatherosclerosis). A 60 year-old male with previous medical history of hypertension, hyperlipidemia, and coronary artery bypass grafting, developed ISR of a 3.5 × 32 mm paclitaxel-eluting stent two years after its implantation,
⁎ Corresponding author at: Department of Cardiology, Ferrarotto Hospital, University of Catania, Via Citelli 1, 95100, Catania, Italy. Fax: +39 095 743 6105. E-mail address: [email protected] (G.F. Attizzani).
which was treated with plain balloon angioplasty. Four years later, he presented with stable angina and lateral ischemia in myocardial perfusion scintigraphy. Angiography depicted recurrence of ISR without further remarks and OCT identified different patterns of low-signal intensity tissue (LSIT) as components of ISR, namely lipid-laden tissue and a layered, “black-hole”-like vascular reaction (i.e., neoatherosclerosis) [5–7]. After lesion preparation with a 3.0 × 15 mm semi-compliant balloon dilation, a 3.0 × 18 mm BVS was implanted intra-stent with good results [8] (Fig. 1). Patient returned for control angiography and OCT at 9-month follow-up. While bright, normal appearing tissue was demonstrated covering most of BVS struts, layered LSIT was still present in some regions in which it had been detected pre-BVS implantation (Fig. 2). Whether this finding corresponds to ongoing healing process at a relatively early follow-up (i.e., 9-month) or will remain later in time (i.e., delayed healing) demands further OCT assessment [9]. The best treatment strategy in patients with DES ISR is still uncertain. Since several different mechanisms, with different prognosis, may lead to this pathological phenomenon, a more individualized rather than a generalized approach may be more suitable in this scenario. The rationale for using an everolimus-eluting BVS in this case was based on the qualitative information provided by OCT imaging pre-procedure (i.e, late abnormal vascular response) [10]. As opposed to the implantation of another metallic DES intra-stent, BVS implantation prevents the presence of double metal layer and eventual longterm exposure of metallic struts to coronary circulation in case of persistently delayed healing. Although drug-eluting balloon intervention was also initially considered as an option for this patient, we decided not to use paclitaxel (i.e., drug component of commercially available drug-eluting balloons) recurrently as the drug of choice to inhibit neointimal formation in this case, since it is difficult to prove which components (i.e., persistent polymer and/or eluting drug) of the previously implanted paclitaxel-eluting stent were responsible for the delayed healing initially observed. To date, everolimus-eluting BVS implantation for in-stent restenosis is considered an “off-label” indication and further prospective studies are warranted to assess the safety and efficacy of this therapy. Dr. Attizzani reports receiving consulting fees from St Jude Medical, Inc. Other authors report no relevant conflicts of interest.
4489
Stress-induced cardiomyopathy in the critically ill — Why inotropes fail to improve outcome Bjorn Redfors a,b,⁎, Yangzhen Shao a, Elmir Omerovic a,b a b
Wallenberg Laboratory at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
a r t i c l e
i n f o
Article history: Received 20 May 2013 Accepted 30 June 2013 Available online 18 July 2013 Keywords: Stress-induced cardiomyopathy Inotropes Catecholamines Intensive care unit
Cardiac dysfunction is common in ICU patients and is a poor prognostic factor [1,2]. Acute myocardial infarction (AMI) is commonly diagnosed in ICU patients and cardiospecific proteins are detected in up to 47% of these patients. An AMI diagnosis is often based only on detection of cardiospecific proteins in plasma and/or ECG and echocardiographic findings. Angiographic evidence is rarely present [2]. Furthermore, reported plasma troponin levels are often mildly to moderately elevated, a laboratory finding that is consistent not only with a small or moderately sized AMI but also with stress-induced cardiomyopathy (SIC). It is thus possible that many or perhaps most cases of myocardial infarction diagnosed in the ICU may in fact be SIC. SIC was first described in 1990 but is now an increasingly recognized acute cardiac syndrome and an important differential diagnosis in patients presenting with chest pain [3]. SIC is characterized by severe regional myocardial hypokinesia or akinesia, often but not always involving apical segments, in the absence of an explanatory coronary lesion [4]. Although the pathomechanisms behind SIC is believed to differ substantially from that of AMI the two conditions appear clinically similar and cannot, as yet, be differentiated by non-invasive modalities [5]. However, plasma troponin levels are typically mildly to moderately elevated in SIC and extreme values are rare. SIC is typically preceded by an emotional or somatic stressor and although the pathophysiology of SIC is poorly understood, there exist strong evidence for an important role of catecholamine overstimulation [5]. Among the evidence indicating catecholamines in the pathogenesis of SIC are the observations that plasma levels of epinephrine and norepinephrine are severely elevated in SIC patients, also compared to AMI patients, and several reports where iatrogenously administered beta-adrenergic agonists have triggered SIC or worsened the patients' condition [5,6]. Furthermore, we have shown that i.p. administration of isoprenaline, a nonselective β-adrenoreceptor agonist, induces SIC-like left ventricular apical akinesia in rats [7]. We believe that there is reason to believe that SIC may be particularly prevalent among patients admitted because of severe non-cardiac disease, conditions associated with internal somatic stress and a strong adrenergic drive. A recent report showed that N20% of patients admitted to an intensive care unit (ICU) displayed SIC-like left ventricular apical ballooning. Development of SIC-like cardiac dysfunction was particularly likely in sepsis, a condition associated with a profound endogenous stress response [1].
⁎ Corresponding author at: Bruna stråket 16, SE 413 45 Gothenburg, Sweden. Tel.: + 46 31 343 7560; fax: + 46 31 823762. E-mail address: [email protected] (B. Redfors).
Considering the liberal use of inotropic support in ICU patients, including catecholamine, detection of SIC patients in this setting may be of particular importance and may merit re-evaluation of treatment strategies [6,8]. Cardiac output is often inadequate in ICU patients despite optimization of filling pressures and afterload. These patients therefore require additional support to maintain adequate tissue perfusion. Typical regimens include positive inotropes and/or vasopressor substances, many of which are catecholamines. We believe that further stimulation of adrenergic signaling pathways may exacerbate cardiac dysfunction in some patients and may lead to paradoxical deterioration of these patients condition (Fig. 1). In patients suffering from severe heart failure inotropic support by the β-adrenoreceptor agonist dobutamine was associated with a near statistically significantly increased mortality compared to placebo [8]. We believe that suspicion of stress-induced cardiac dysfunction should deter the anesthesiologist towards switching to non-catecholamine vasopressors. Similarly, non-catecholamine vasopressors may also be preferable in these patients. We propose that many so-called AMIs detected in the ICU may in fact be SIC and in many cases these SICs may have been caused or exacerbated by iatrogenously administered inotropic agents, especially β-adrenoreceptor agonist. Non-catecholamine inotropes and/or vasopressors or mechanical assist may be preferable in patients at risk of developing SIC. Until SIC is better understood and these patients can be identified we argue for judicious use of catecholamine inotropes and liberal use of mechanical assist, particularly in patients displaying signs of cardiac dysfunction or injury.
Fig. 1. Vicious cycle of inotropic support in stress-induced cardiomyopathy. Catecholamine vasopressor and inotropes administered to improve cardiac functional impairment and hypotension may instead further worsen cardiac function. This in turn aggravates hypotension and may lead to a decision to increase catecholamine doses.
4490
Letters to the Editor
References [1] Park JH, Kang SJ, Song JK, et al. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest 2005;128:296–302. [2] Lim W, Qushmaq I, Cook DJ, et al. Elevated troponin and myocardial infarction in the intensive care unit: a prospective study. Crit Care 2005;9:R636–44. [3] Shao Y, Redfors B, Lyon AR, Rosengren A, Swedberg K, Omerovic E. Trends in publications on stress-induced cardiomyopathy. Int J Cardiol 2012;157:435–6. [4] Schultz T, Shao Y, Redfors B, et al. Stress-induced cardiomyopathy in Sweden: evidence for different ethnic predisposition and altered cardio-circulatory status. Cardiology 2012;122:180–6.
[5] Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539–48. [6] Redfors B, Shao Y, Omerovic E. Stress-induced cardiomyopathy in a patient with chronic spinal cord transection at the level of C5: endocrinologically mediated catecholamine toxicity. Int J Cardiol 2012;159:e61–2. [7] Shao Y, Redfors B, Scharin Tang M, et al. Novel rat model reveals important roles of betaadrenoreceptors in stress-induced cardiomyopathy. Int J Cardiol 2013;168(3):1943–50. [8] Tacon CL, McCaffrey J, Delaney A. Dobutamine for patients with severe heart failure: a systematic review and meta-analysis of randomised controlled trials. Intensive Care Med 2012;38:359–67.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.06.128
First-in-human description of everolimus-eluting bioabsorbable vascular scaffold implantation for the treatment of drug-eluting stent failure: Insights from optical coherence tomography Carmelo Grasso a, Guilherme F. Attizzani a,⁎, Martina Patané a, Yohei Ohno a, Davide Capodanno a,b, Corrado Tamburino a,b a b
Division of Cardiology, Ferrarotto Hospital, University of Catania, Italy Excellence Through Newest Advances (ETNA) Foundation, Catania, Italy
a r t i c l e
i n f o
Article history: Received 21 May 2013 Accepted 30 June 2013 Available online 24 July 2013 Keywords: Bioresorbable vascular scaffold In-stent restenosis Optical coherence tomography
Drug-eluting stents (DES) markedly reduce new episodes of revascularization compared with bare-metal stents; nevertheless, the prevalence of DES in-stent restenosis (ISR) is not insignificant as a large population is treated with these devices worldwide [1]. In addition, concerns regarding long-term safety of metallic DES [2] stimulated investigators to seek for improvement of this therapy. Everolimuseluting bioabsorbable vascular scaffolds (BVS, Abbott Vascular, Santa Clara, CA, USA) emerged as an interesting alternative, as they enable vessel scaffolding in short-term and anti-restenotic drug delivery, while avoiding long-term limitations of metallic DES (i.e., prolonged metal exposure to coronary circulation in case of delayed healing). Indeed, BVS demonstrated promising results in the treatment of de novo coronary lesions [3]. Meanwhile, optical coherence tomography (OCT) imaging was proved the most suitable intravascular imaging modality to assess BVS-vessel interactions in vivo [4]. Nevertheless, the use of BVS in the treatment of ISR has never been documented. We report for the first time, baseline and 9-month follow-up OCT assessments of BVS implantation for the treatment of DES failure (i.e., recurrent DES ISR and neoatherosclerosis). A 60 year-old male with previous medical history of hypertension, hyperlipidemia, and coronary artery bypass grafting, developed ISR of a 3.5 × 32 mm paclitaxel-eluting stent two years after its implantation,
⁎ Corresponding author at: Department of Cardiology, Ferrarotto Hospital, University of Catania, Via Citelli 1, 95100, Catania, Italy. Fax: +39 095 743 6105. E-mail address: [email protected] (G.F. Attizzani).
which was treated with plain balloon angioplasty. Four years later, he presented with stable angina and lateral ischemia in myocardial perfusion scintigraphy. Angiography depicted recurrence of ISR without further remarks and OCT identified different patterns of low-signal intensity tissue (LSIT) as components of ISR, namely lipid-laden tissue and a layered, “black-hole”-like vascular reaction (i.e., neoatherosclerosis) [5–7]. After lesion preparation with a 3.0 × 15 mm semi-compliant balloon dilation, a 3.0 × 18 mm BVS was implanted intra-stent with good results [8] (Fig. 1). Patient returned for control angiography and OCT at 9-month follow-up. While bright, normal appearing tissue was demonstrated covering most of BVS struts, layered LSIT was still present in some regions in which it had been detected pre-BVS implantation (Fig. 2). Whether this finding corresponds to ongoing healing process at a relatively early follow-up (i.e., 9-month) or will remain later in time (i.e., delayed healing) demands further OCT assessment [9]. The best treatment strategy in patients with DES ISR is still uncertain. Since several different mechanisms, with different prognosis, may lead to this pathological phenomenon, a more individualized rather than a generalized approach may be more suitable in this scenario. The rationale for using an everolimus-eluting BVS in this case was based on the qualitative information provided by OCT imaging pre-procedure (i.e, late abnormal vascular response) [10]. As opposed to the implantation of another metallic DES intra-stent, BVS implantation prevents the presence of double metal layer and eventual longterm exposure of metallic struts to coronary circulation in case of persistently delayed healing. Although drug-eluting balloon intervention was also initially considered as an option for this patient, we decided not to use paclitaxel (i.e., drug component of commercially available drug-eluting balloons) recurrently as the drug of choice to inhibit neointimal formation in this case, since it is difficult to prove which components (i.e., persistent polymer and/or eluting drug) of the previously implanted paclitaxel-eluting stent were responsible for the delayed healing initially observed. To date, everolimus-eluting BVS implantation for in-stent restenosis is considered an “off-label” indication and further prospective studies are warranted to assess the safety and efficacy of this therapy. Dr. Attizzani reports receiving consulting fees from St Jude Medical, Inc. Other authors report no relevant conflicts of interest.