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Objective To evaluate the long-term efficacy of three currently available drug coated balloons (DCB) for the treatment of de-novo coronary lesions. Methods This was a retrospective analysis of prospectively collected data from the Swedish Coronary Angiography and Angioplasty Registry. Between 2009 and 2017, three currently available DCB brands used in the treatment of de novo lesions were included. Outcomes were clinically driven restenosis and target lesion thrombosis (TLT) (per device) and major adverse cardiac events (MACE) including death, myocardial infarction or target vessel revascularization (per patient) at 4 years. Multivariable Cox regression models were used to adjust for differences. Results We included 6715 lesions treated with DCBs, 4483 SeQuent® Please (S-DCB), 1071 IN.PACT Falcon (I-DCB) and 1161 Pantera® Lux (P-DCB), in 5670 patients. The mean DCB diameter was 2.4 mm. Bailout stenting occurred in 6.7% of lesions. Angiographic success was 98.5%. The overall cumulative rate of restenosis was 5.5% (299 events). The risk for reported restenosis did not significantly differ between I-DCB vs S-DCB, adjusted hazard ratio (aHR) 0.96; 95% confidence interval (CI) 0.69–1.34, P-DCB vs S-DCB aHR 0.88; 95% CI 0.63–1.23 and I-DCB vs P-DCB aHR 1.10; 95% CI 0.72–1.68. The cumulative risk for TLT was 0.8% in all three DCBs. The risk for MACE or individual components of MACE did not differ between the three patient-groups. Conclusion In de novo coronary lesions, we found comparable long-term efficacy with three currently available DCB brands. DCB angioplasty was feasible with low risk for long-term restenosis and TLT.

Background Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome. However, little is known about risk factors for worse outcomes in TS and no high-risk ECG criteria have been defined. We sought to identify ECG predictors of life-threatening in-hospital complications in TS. Method and result Using the nationwide Swedish Angiography and Angioplasty Registry (SCAAR) we obtained data on all consecutive patients undergoing coronary angiography at Sahlgrenska University Hospital between June 2008 and February 2019. For all patients with TS we conducted in-depth chart reviews to confirm the TS diagnosis. For those with confirmed TS we then evaluated all ECGs obtained during the index hospitalization. The primary endpoint was the occurrence of in-hospital major adverse cardiac event (MACE), defined as the composite of death, ventricular tachycardia or fibrillation (VT/VF), or atrioventricular block ≥2 or asystole ≫10 s. We identified 215 patients with TS (mean age 69 ± 13 years; 93% women). MACE occurred in 34 patients (16%), of whom 20 had VT/VF (9,3%). Patients with MACE were less likely than those without MACE to have sinus rhythm (85% versus 96%, p = 0.025) or T-wave inversion (29% versus 51%, p = 0.025). After propensity score adjustment T-wave inversion was independently associated with lower MACE risk (adjusted odds ratio [AdjOR] 0.28, 95% confidence interval [CI] 0.10–0.76, p = 0.012) and VT/VF (AdjOR 0.24, 95% CI 0.06–0.94, p = 0.041). Conclusion T-wave inversion is common in TS and is associated with lower risk of MACE, driven by a lower risk of VT/VF.

BACKGROUND: Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization.METHODS: In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result.RESULTS: The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions.CONCLUSIONS: IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.

Background Takotsubo syndrome (TS) is an acute cardiac syndrome characterized by regional myocardial akinesia that is not caused by coronary artery occlusion. Exogenous as well as endogenous excess catecholamines can induce TS. The aim of this study was to explore the effects of pharmacological cardio-simulative and cardio-depressing drugs on the development of isoprenaline-induced takotsubo-like cardiac dysfunction, a rat model of TS. Methods We randomized 295 rats into twelve groups. The animals were randomized to pre-treatment with either a low or high dose of metoprolol, propranolol, ICI 118551 (beta2-receptor antagonists), milrinone (phosphodiesterase inhibitor), levosimendan or saline (control) before induction of TS with isoprenaline. In one additional group, high dose of milrinone was administered alone. We measured invasively blood pressure and heart rate over a period of 90 min. Cardiac function and morphology were evaluated with high-resolution echocardiography. Results Milrinone alone induced apical ballooning similar to isoprenaline. Pretreatment with propranolol and metoprolol but not with ICI 118551 attenuated takotsubo-like akinesia in a dose-dependent manner. Pretreatment with metoprolol decreased mortality. Pretreatment with levosimendan resulted in higher incidence of apical ballooning while pretreatment with milrinone did not change the degree of akinesia. Conclusion The phosphodiesterase inhibitor milrinone induces takotsubo-like dysfunction in the absence of exogenous catecholamines. This finding challenges the concept that high levels of circulating catecholamines or excessive stimulation of adrenergic receptors are necessary for the development of takotsubo syndrome. Our study provides experimental evidence for the concept of avoidance of inotropes and that selective beta1-blockade may be beneficial in the treatment of TS-patients.

Background Type 2 diabetes is a major health problem in the world, and is strongly associated with impaired cardiac function and increased mortality. The causal relationship between type 2 diabetes and impaired cardiac function is still incompletely understood but changes in the cardiac lipid metabolism are believed to be a contributing factor. The objective of this study was to determine the lipid profile in human myocardial biopsies collected in vivo from patients with type 2 diabetes and compare to non-diabetic controls. Method We conducted full lipidomics analyses, using mass spectrometry, of 85 right atrial biopsies obtained from diabetic and non-diabetic patients undergoing elective cardiac surgery. The patients were characterized clinically and serum was analyzed for lipids and biochemical markers. Results The groups did not differ in BMI and in circulating triglycerides. We demonstrate that type 2 diabetes is associated with alterations in the cardiac lipidome. Interestingly, the absolute amount of lipids is not altered in the diabetic myocardium. However, triglycerides with longer fatty acyl chains are more abundant and there is a higher degree of unsaturated fatty acid chains in triglycerides in diabetic myocardium. Conclusions Our study reveals that type 2 diabetes is a relatively strong determinant of the human cardiac lipidome (compared to other clinical variables). Although the total lipid content in the diabetic myocardium is not increased, the lipid composition is markedly affected.

BackgroundMyocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia.Methods and resultsWe generated Plin5−/− mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5−/− mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction.ConclusionOur findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia.

Cardiogenic shock remains the leading cause of in hospital death in acute myocardial infarction (AMI) and is associated with a mortality rate of approximately 50%. Here we investigated the 17-year trends in incidence and prognosis of AMI-induced cardiogenic shock in Västra Götaland in western Sweden, an area with approximately 1.6 million inhabitants. The study period includes the transition from thrombolysis to primary percutaneous coronary intervention (PCI) as the region-wide therapy of choice for patients with ST-elevation myocardial infarction (STEMI).Data on patients hospitalized in cardiac care units in Västra Götaland, Sweden between 1995 and 2013 were obtained from the Swedish Websystem for Enhancement of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). We determined the incidence of cardiogenic shock among patients diagnosed with AMI and the risk of death associated with developing cardiogenic shock. We fitted logistic regression models to study which factors predicted post-AMI cardiogenic shock. Analyses were performed on complete case data as well as after multiple imputation of missing data.Incidence of cardiogenic shock as a complication of AMI declined in western Sweden in the past decade, from 14% in 1995 to 4% in 2012. The risk of dying once cardiogenic shock had developed increased during the study period (p0.01). Patients presenting with STEMI were more likely to develop cardiogenic shock than patients presenting with non STEMI (p0.001).The incidence of cardiogenic shock has declined but cardiogenic shock carries a worse prognosis today than in 1995.

Background Takotsubo syndrome is an acute cardiovascular condition that predominantly affects women. In this study, we compared patients with takotsubo syndrome and those with acute myocardial infarction with respect to patient characteristics, angiographic findings, and short- and long-term mortality. Methods From the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA), we obtained and merged data on patients undergoing coronary angiography in Vastra Gotaland County in western Sweden between January 2005 and May 2013. Short- and long-term mortality in patients with takotsubo ( n =302) and patients with ST-elevation myocardial infarction (STEMI, n =6595) and non-ST-elevation myocardial infarction (NSTEMI, n =8207) were compared by modeling unadjusted and propensity score–adjusted logistic and Cox proportional-hazards regression. Results The proportion of the patients diagnosed with takotsubo increased from 0.16% in 2005 to 2.2% in 2012 ( P Conclusions The proportion of acute coronary syndromes attributed to takotsubo syndrome in Western Sweden has increased over the last decade. The prognosis of takotsubo syndrome is poor, with similar early and late mortality as STEMI and NSTEMI.

Previous studies have established a relationship between socioeconomic status (SES) and survival in coronary heart disease. Acute cardiac care in Sweden is considered to be excellent and independent of SES. We studied the influence of area-level socioeconomic status on mortality after hospitalization for acute myocardial infarction (AMI) between 1995 and 2013 in the Gothenburg metropolitan area, which has little over 800,000 inhabitants and includes three city hospitals.Data were obtained from the SWEDEHEART registry (Swedish Websystem for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and the Swedish Central Bureau of Statistics for patients hospitalized for ST-elevation myocardial infarction (STEMI) and non-STEMI in the city of Gothenburg in Western Sweden. The groups were compared using Cox proportional hazards regression and logistic regression.10,895 (36% female) patients were hospitalized due to AMI during the study period. Patients residing in areas with lower SES had higher rates of smoking and diabetes (P0.001), and were also at increased risk of developing complications, including heart failure and cardiogenic shock (P0.05). Living in an area with lower SES associated with increased risk of dying after an AMI also in models adjusted for risk factors (P0.05).Also in a country with strong egalitarian traditions, lower SES associates with worse prognosis after AMI, an association that persists after adjustments for differences in traditional cardiovascular risk factors.

Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, is an acute cardiac syndrome. The unique characteristics of TTS are that one or more circumferential cardiac segments are stunned out of contraction in the absence of an explanatory coronary lesion [1]. Although the peculiar myocardial akinesia can affect any part of the ventricular wall, two common patterns of TTS are apical akinesis (the typical TTS) and basal akinesis (the inverted pattern) [2]. The pathogenesis underlying Takotsubo syndrome is incompletely understood. Several mechanisms have been proposed for the development of TTS, including overstimulation of the β2-adrenoceptor-Gi pathway [3], acute coronary microvascular and endothelial dysfunction [4], aborted myocardial infarction with spontaneous recanalisation [5], acute metabolic stunning [6], lipotoxicity [1,7], acute left ventricular outflow tract obstruction (LVOTO) and abnormal ventriculo-arterial coupling [8]. One critical shortcoming of some of these proposed mechanisms is that they are not able to elucidate why myocardial akinesia in TTS is usually segmental and circumferential. Although the gradient distribution of β-adrenoceptors or sympathetic nerves in the heart may explain why catecholamine-induced myocardial akinesia can be apical or basal, such physiological properties, including genetic profiles, currently fail to

Takotsubo syndrome is an increasingly recognized acute cardiac affliction which is characterized by severe regional left ventricular dysfunction that cannot be explained by one or more occlusive culprit lesions of a coronary artery. A preceding somatic and/or emotional stressor can be identified in a majority of these patients and older women are overrepresented among the afflicted. Catecholamine levels are elevated in patients with takotsubo and exogenous catecholamine administration may cause or exacerbate the condition. Hence, catecholamines appear implicated in the pathogenesis. However, beyond catecholamine the pathogenesis of the takotsubo syndrome is unclear. Five distinct hypotheses have been postulated which attempt to explain why specific regions within the left ventricle are affected in takotsubo. In this manuscript we critically review these hypotheses in light of the available data. We discuss how the different hypotheses may be complementary to each other and to which extent they are contradicting one another.

Background Stress-induced cardiomyopathy (SIC) is a common syndrome with substantial morbidity and mortality. SIC is common in intensive care units' patients. No therapeutic intervention for SIC has been evaluated in randomized clinical trial so far. Our aim was to investigate whether isoflurane is cardioprotective in an experimental SIC model. Methods We induced SIC-like cardiac dysfunction in rats with intraperitoneal injection of isoprenaline (50mg/kg) and performed this study in two parts. First, we pre-treated rats with isoflurane (1.5%, n=12), pentobarbital (50mg/kg, n=12) and ketamine (80mg/kg, n=12) and compared to controls (n=12). We used glyburide, an ATP-dependent potassium channel blocker (n=6), to test whether isoflurane-protection is mediated through K ATPm . In a second set of experiments, we treated rats with two different doses of isoflurane i.e. 0.75% (n=12) and 1.5% (n=12) before induction of SIC and compared to controls. We assessed left ventricular function and morphology in all rats by transthoracic echocardiography. We also measured peak body temperature, blood gases, acid–base homeostasis, blood pressure and heart rate. Results The extent of apical akinesia was lowest and cardiac function was best in the isoflurane treated rats. The protective effects were not attenuated by glibenclamide. Higher dose of isoflurane was more cardioprotective than the lower dose. This was persistent after the adjustment for changes in hemodynamics and blood biochemistry induced by anesthesia. Conclusions Isoflurane prevented SIC-like cardiac dysfunction in rats. This protection was not mediated via K ATPm . Our study provides an experimental foundation for future clinical trials in SIC.

[1] Dominguez-Rodriguez A, Abreu-Gonzalez P. The link between sleep duration and inflammation: effects on cardiovascular disease. Int J Cardiol 2014;173(3):600–1. [2] Cheng Y, DuCL, Hwang JJ, Chen IS, ChenMF, Su TC.Working hours, sleep duration and the risk of acute coronary heart disease: a case–control study ofmiddle-agedmen in Taiwan. Int J Cardiol 2014;171:419–22. [3] Kawada T. Working hours, sleep duration and risk of coronary heart disease. Int J Cardiol 2014;174(1):162.

Takotsubo cardiomyopathy (TCM) is characterized by regional left ventricular dysfunction that cannot be explained by an occlusive lesion in a coronary artery. Catecholamines are implicated in the pathogenesis of TCM but the mechanisms involved are unknown. Because the endogenous and the most commonly used exogenous catecholamines have well defined adrenoceptor subtype affinities, inferences can be made about the importance of each adrenoceptor subtype based on the ability of different catecholamines to induce TCM. We therefore studied which of five well-known catecholamines, that differ in receptor subtype affinity, are able to induce TCM-like cardiac dysfunction in the rat.255 rats received intraperitoneally isoprenaline (β1/β2-adrenoceptor agonist), epinephrine (β1/β2/α-adrenoceptor agonist), norepinephrine (β1/α-adrenoceptor agonist), dopamine (α/β1/β2-adrenoceptor agonist) or phenylephrine (α-adrenoceptor agonist). Each catecholamine was given in five different doses. We measured blood pressure through a catheter inserted in the right carotid artery and studied cardiac morphology and function by echocardiography.All catecholamines induced takotsubo-like cardiac dysfunction. Isoprenaline induced low blood pressure and predominantly apical dysfunction whereas the other catecholamines induced high blood pressure and basal dysfunction. In another set of experiments, we continuously infused hydralazine or nitroprusside to rats that received epinephrine or norepinephrine to maintain systolic blood pressure120 mm Hg. These rats developed akinesia of the apex instead of the base. Infusion of phenylephrine to maintain blood pressure120 mm Hg after isoprenaline administration prevented apical TCM-like dysfunction.Catecholamine-induced takotsubo-like cardiac dysfunction appears to be afterload dependent rather than depend on stimulation of a specific adrenergic receptor subtype.

Without a heart transplant, 20% of patients with end-stage heartfailure will die within 6 months. If the patient receives a new heart,however, the estimated median survival time exceeds 10 years [1].Unfortunately, because of the paucity of donors who meet the criteriafortransplantation[2,3],heartsareavailableforonlyasmallpercentageof recipients with refractory heart failure who are eligible for hearttransplantation. Current guidelines stipulate that donor hearts shouldnot have wall motion abnormalities and that ejection fraction shouldbe over 40% [4].Takotsubo syndrome is an acute condition with characteristicreversible regional wall motion abnormalities and decreased ejectionfraction. Takotsubo frequently affects patients with severe somaticdisease [5] and is common in patients with cerebral lesions, includingsubarachnoid hemorrhage [5]. The current guidelines do not mentionwhether patients with brain death and takotsubo could be consideredas organ donors.The process of brain death elicits significant somatic stress and acatecholamine surge [6] Increasing evidence suggests that takotsubosyndrome is caused by direct catecholamine toxicity in predisposedpatients and is therefore probably common in patients with braindeath. Here we present a case in which a heart was successfullytransplanted from a donor with wall motion abnormalities due totakotsubo syndrome.

Background Takotsubo syndrome is a form of acute, reversible heart failure that has gained increasing attention. It affects mostly postmenopausal women, and its acute onset and symptoms mimic acute myocardial infarction. The distinct feature of takotsubo syndrome is the ballooning of a ventricle, but the complete pathophysiological mechanisms are not fully understood. Both short-term and long-term survival are affected, but little is known about the illness experience and self-reported residual symptoms after discharge from hospital. Aim To measure and compare self-reported residual symptoms between patients with takotsubo syndrome and those with acute myocardial infarction. Method Questionnaire data measuring self-reported symptoms were collected from 48 patients with takotsubo syndrome and 79 patients with acute myocardial infarction 8weeks after discharge. A multivariate adjusted complete case regression model was used to compare the frequency and severity of symptoms. Results Self-reported symptoms 8weeks after discharge differed little between patients with takotsubo syndrome and those with acute myocardial infarction. Both groups reported symptoms, including pain, fatigue, breathlessness, and sleep disturbance. At onset there were significant differences between the groups concerning previous diabetes mellitus, cardiac troponin T, ejection fraction and Killip class. There were no significant between-group differences in frequency or severity of symptoms after adjusting for these differences. Conclusion Patients with takotsubo syndrome experience residual symptoms after discharge. Symptoms in several cardiovascular diseases predict quality of life, re-admission, and mortality. Symptom management should be integrated into follow-up care for patients with takotsubo syndrome. One way of achieving this is through person-centered care.

Takotsubo syndrome is an acute cardiovascular condition that predominantly affects women. In this study, we compared patients with takotsubo syndrome and those with acute myocardial infarction with respect to patient characteristics, angiographic findings, and short- and long-term mortality.From the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA), we obtained and merged data on patients undergoing coronary angiography in Västra Götaland County in western Sweden between January 2005 and May 2013. Short- and long-term mortality in patients with takotsubo (n=302) and patients with ST-elevation myocardial infarction (STEMI, n=6595) and non-ST-elevation myocardial infarction (NSTEMI, n=8207) were compared by modeling unadjusted and propensity score-adjusted logistic and Cox proportional-hazards regression.The proportion of the patients diagnosed with takotsubo increased from 0.16% in 2005 to 2.2% in 2012 (P0.05); 14% of these patients also had significant coronary artery disease. Cardiogenic shock developed more frequently in patients with takotsubo than NSTEMI (adjusted OR 3.08, 95% CI 1.80-5.28, P0.001). Thirty-day mortality was 4.1% and was comparable to STEMI and NSTEMI. The long-term risk of dying from takotsubo (median follow-up 25 months) was also comparable to NSTEMI (adjusted HR 1.01, 95% CI 0.70-1.46, P=0.955) STEMI (adjusted HR 0.83, 95% CI 0.57-1.20, P=0.328).The proportion of acute coronary syndromes attributed to takotsubo syndrome in Western Sweden has increased over the last decade. The prognosis of takotsubo syndrome is poor, with similar early and late mortality as STEMI and NSTEMI.

In the normally contracting heart, the contractile apparatus consumes the great majority of myocardial energy metabolites and oxygen. In fact, non-contractile myocardial functions, including cardiac action potentials as well as maintenance of cellular homeostasis, require less than 20% as much oxygen [1]. It is therefore apparent that shutting down the hearts' mechanical activities during severe oxygen deprivation could preserve energy metabolites. In fact, this is what happens during ischemic stunning. We believe that the same mechanisms are at play in takotsubo, another conditions in which the cardiomyocytes sense relative oxygen deprivation. The heart relies almost entirely on aerobic metabolism and is dependent on a continuous supply of oxygen. In healthy subjects the heart can increase regional blood flow at least 5-fold through socalled autoregulatory mechanisms and can therefore tolerate fluctuations in myocardial oxygen demand. However, situations can arise where autoregulatory mechanisms fail to maintain adequate tissue perfusion. This leads to myocardial ischemia. If the supply:demand mismatch is of sufficient magnitude and duration cardiomyocyte cell death ensues. Following complete occlusion of a coronary artery, cardiomyocytes supplied by that artery stop contracting within seconds. Energy metabolites decrease to 50% of their initial levels within 10 min and within 20 min irreversible cell injury ensues. Thus, contractile activities cease well before the cell is depleted of energy, a phenomenon coined “ischemic stunning”. Such a hierarchical order of cellular functions is reasonable from an evolutionary perspective and is common in biology. By downprioritizing contractile activities the cell preserves energy and is able to sustain longer periods of oxygen deprivation. Hence, although it inherently leads to impaired cardiac function with potential complications, ischemic stunning is likely an important protective mechanism in acute ischemic syndromes, including acute myocardial infarction. Pre-, perand postconditioning are terms used to describe the protective effect on the myocardium of brief episodes of ischemia against subsequent, simultaneous, or preceding greater ischemic insults. A great myriad of molecules have been postulated to mediate conditioning but none have been successfully translated to clinical praxis. It is clear from earlier studies that ischemic conditioning phenomena entail more thanmerely ischemic stunning, i.e. preservation of energy metabolites otherwise destined to be consumed by the contractile apparatus. Studies have shown that brief episodes of ischemia preceding an ischemic event are associated with cardioprotection independent on the degree of functional impairment still present at the onset of the indexevent [2]. This is not surprising since ischemic stunning likely ensues immediately upon coronary artery occlusion. Thus, since little energy is lost before stunning ensues, little if any benefit would be expected if the myocardium was already stunned beforehand. Instead, conditioning more likely probes the heart towards more efficient “stunning” once the ischemic insult occurs. This is most likely accomplished by complex intracellular alterations, some of which have been thoroughly studied. Takotsubo is characterized by regional contractile dysfunction that develops in the absence of an explanatory vascular culprit lesion and that often extends beyond the territory supplied by a single main coronary artery. Catecholamines are strongly implicated in the pathogenesis and a strong emotional and/or physical stressor can be identified in the majority of patients [3]. Although the mechanisms underlying takotsubo are incompletely understood, there is indirect support in the literature for a causative role of relative ischemia. First, microvascular resistance has been shown to be increased in patients with takotsubo [4]. Second, and more important, left ventricular outflow obstruction can be observed at the time of echocardiographic assessment in approximately 1/4 of patients that present with typical takotsubo, i.e. apical akinesia with preserved basal function [5]. The combination of strong inotropic drive and outflow obstruction could be expected to greatly increase LV afterload, particularly in apical regions. Cardiomyocytes within

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. SICwas first described in 1990 but is nowan 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]. 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 ICUpatients despite optimization of filling pressures and afterload. These patients therefore require additional support tomaintain adequate tissue perfusion. Typical regimens include positive inotropes and/or vasopressor substances, manyofwhich are catecholamines.Webelieve that further stimulation of adrenergic signaling pathways may exacerbate cardiac dysfunction in somepatients andmay lead toparadoxical 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.

Stress-induced cardiomyopathy (SIC) is characterized by transient extensive left ventricular (LV) akinesia in the absence of coronary artery disease of sufficientmagnitude to explain the extent of cardiac dysfunction. The typical presentation is that of an akinetic ballooning apexwith hypercontractile basal segments. Stress-induced release of catecholamines is believed to trigger cardiac dysfunction, but it is not known whether it is mediated by systemically elevated plasma catecholamines (endocrine hypothesis) or by the sympathetic nervous end (neural hypothesis) [1]. Here we present a near-fatal case of stress-induced cardiomyopathy (SIC) following opioid withdrawal in a young tetraplegic man. A 34-year-old tetraplegic man was admitted to our hospital for removal of a spinal opioid analgesic pump. Two years earlier, the patient was involved in a vehicle accident in which he suffered a spinal cord transection at the level of C5–C6. Since then, he had suffered from chronic pain for which he had the analgesic pump implanted. After a withdrawal period of 10 days, he developed dyspnea and cramps. Chest X-ray revealed pulmonary edema. He was febrile and antibiotic treatment was started. The patient was transferred to the intensive care unit where he was subsequently intubated and given intravenous inotropic support. The following day, his condition deteriorated and a decision wasmade to initiate extracorporeal membranous oxygenation (ECMO) treatment. Preoperative echocardiography demonstrated a completely akinetic apex with contractions only in the most basal parts of the left ventricle (LV) (Fig. 1A; Supplemental video 1). The right ventricule was also severely affected. During surgi