Stress-induced Cardiomyopathy Research Articles

A Case of Stress-Induced Cardiomyopathy After Ketamine Infusion

A Case of Stress-Induced Cardiomyopathy After Ketamine Infusion

Takotsubo cardiomyopathy after solid organ transplantation: a scoping review.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that causes temporary left ventricular wall motion abnormalities and abrupt reversible heart failure. The incidence of perioperative TTS is proportional to the severity of surgical trauma, the duration of the procedure, and the degree of apparent sympathetic activity. A growing number of articles have discussed TTS after a solid organ transplant (SOT), which is one of the circumstances in which physical and emotional stress are at their highest levels. The majority of published cases involved patients who had received an orthotopic liver transplant (OLT). TTS occurred in 0.3-1.7% of liver transplant recipients, but a limited number of cases of TTS in patients who had received kidney, heart, or lung transplants have also been documented. In this study, we analyzed the TTS instances that developed after SOT, highlighting the symptoms and causes as well as the various treatment approaches that were applied. Most TTS cases following OLT and kidney transplant cases occurred in the first week of the surgery. However, the majority of cases occurred years after heart transplantation. Dizziness, dyspnoea, and chest discomfort are the most typical symptoms. Patients may also experience syncope and generalized weakness. In spite of this, the symptoms differ depending on the transplanted organ. Dyspnoea is a common symptom after lung transplants, whereas chest discomfort and dizziness are a common symptom after liver and kidney transplants. Yet, chest pain is not a typical symptom after a heart transplant.

(1278) - Isolated Right Heart Stress-Induced Cardiomyopathy After Lung Transplant

(1278) - Isolated Right Heart Stress-Induced Cardiomyopathy After Lung Transplant

‘Wilt Break My Heart?’ Takotsubo Syndrome and Shakespeare’s Discourse of Heartbreak in Antony and Cleopatra and King Lear

ABSTRACT Shakespeare’s characters knew well the dangers and causes of an overcharged heart. This article places representations of heartbreak in Shakespeare’s canon in dialogue with twenty-first-century medical understanding of heartbreak or Takotsubo syndrome (TTS). Over thirty years since its coinage in cardiac medicine, heartbreak syndrome or TTS remains poorly understood. In response to this dearth of information around TTS, this article turns to early modern accounts of heartbreak – particularly its dramatic representation in King Lear and Antony and Cleopatra – and examines these alongside unfolding research into TTS. The essay illuminates a contagious inter-heart dynamic at play in King Lear and analyses best practice treatments for supportive management of stress-induced cardiomyopathy in Antony and Cleopatra. This comparative analysis of broken hearts in Shakespeare and in twenty-first century medical knowledge of TTS aims to offer mutual enlightenment across Shakespeare studies and cardiac medicine.

Histological and functional assessment of a Takotsubo cardiomyopathy model established by immobilization stress.

Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, resembles acute heart failure syndrome but lacks disease-specific diagnosis and treatment strategies. TTC accounts for approximately 5-6% of all suspected cases of acute coronary syndrome in women. At present, animal models of TTC are often created by large amounts of exogenous catecholamines such as isoproterenol. However, isoproterenol injection cannot fully simulate the onset of stress-induced cardiomyopathy in humans since stress is not an instantaneous event. Rats were immobilized for 6h per day for 1-14 days. To examine whether the TTC model was successful, echocardiography was employed; Elisa detected serum sympathetic activation markers; and the Open-Field test (OFT) was used to analyze behavioral changes in rats after stress. Western blot and histology were used to assess sympathetic remodeling, inflammation levels, and fibrosis; qRT-PCR was used to explore the levels of fibrosis and myocardial hypertrophy. The electrical stability of ventricular was determined by electrophysiological testing. The rats showed severe stress behavior and local sympathetic remodeling of the heart after only 1 day of stress. After 3 days of stress, the induction of ventricular tachyarrhythmia increased prominently. The highest incidence of TTC in rats was at 5 days of immobilization stress. The pathological left ventricular remodeling caused by immobilization (IMO) stress includes inflammatory infiltration, fibrosis, and myocardial hypertrophy. Our study confirms the hypothesis that IMO stress can mimic Takotsubo cardiomyopathy, and the various effects on the heart depending on the duration of IMO stress. We observed the highest incidence of TTC occurred after 5 days of stress. Furthermore, there is a gradual occurrence of electrical and structural remodeling as the stress duration prolongs.

Adrenaline bij de behandeling van anafylaxie: hard voor het hart

Adrenaline in the treatment of anaphylaxis: hard for the heart The cornerstone of the treatment of anaphylaxis is adrenaline. The European Resuscitation Council recommends rapid administration by intramuscular route. In addition to acting as a catecholamine on alpha-1, beta-1 and beta-2 adrenergic receptors, it also reduces mediator release from mast cells, decreases obstructive respiratory symptoms and prevents cardiovascular collapse. Serious adverse effects of adrenaline when used in the treatment of anaphylaxis are rare, but can be life-threatening. This case describes a stress-induced (Takotsubo) cardiomyopathy after the erroneous administration of adrenaline via intravenous route instead of intramuscularly in a patient with anaphylaxis. Takotsubo cardiomyopathy is seen in situations of acute stress or intense emotion, mainly in middle-aged women. Clinically, this disease resembles an acute coronary syndrome with an increase in cardiac markers, changes on the electrocardiography (ECG) and reversible left ventricular dysfunction. On a coronarography, however, the coronary arteries are shown to be patent. The exact aetiology is still uncertain. The patient in this case study underwent cardiac catheterisation to rule out primary coronary artery damage and subsequently received a drug treatment with an angiotensin-converting enzyme (ACE) inhibitor and a low-dose beta blocker, in combination with a cardiac rehabilitation programme. The follow-up via a transthoracic echocardiography 1 month later showed a complete recovery of the left ventricular function.

А rare case of Тakoтsubo cardiomyopathy complicated with high-grade AV block and ventricular tachycardia

Takotsubo cardiomyopathy or broken heart syndrome is a stress-induced cardiomyopathy with clinical, laboratory and ECG resemblance to acute coronary syndrome. Major differences stem from transient segmental wall motion abnormalities beyond the territory of a single coronary artery and the lack of obstructive coronary disease during angiography. Overall the condition is considered as a benign one with a favourable outcome, however there are reports of complicated clinical course by cardiogenic shock, apical thrombus, death and arrhythmias. The latter are reported to occur in 13% of the cases with ventricular arrhythmias (ventricular tachycardia, ventricular fi brillation, torsades de pointes) as a leading fi nding and in minor percentage – high-grade AV block. Despite advances in our knowledge and experience there are still no strict guidelines for the management of conduction disorders. We present the case of a 78-year old lady with an apical variant of Takotsubo, complicated by syncope, complete AV block, new left bundle branch block, paroxysmal atrial fi brillation, ventricular tachycardia and implantation of a permanent pacemaker. During the hospitalization she developed acute cardiac failure with echocardiographic evidence of left ventricular systolic dysfunction and an apical thrombus. The presented case demonstrates the complexity of the condition and the necessity of strict follow-up and timely therapy. 

TAKOTSUBO SYNDROME

Takotsubo syndrome, also known as Takotsubo cardiomyopathy, stress-induced cardiomyopathy, transient apical ballooning and broken heart syndrome, is a disease characterized by transient regional left ventricular systolic dysfunction. It is usually determined by emotional or physical stress. Even though it was thought to be a self-limiting condition, Takotsubo syndrome is now known to be associated with important short and long-term morbidity and mortality. Takotsubo syndrome affects 2-3% of all patients and 5-6% of female patients presenting with acute coronary syndrome (frequently women in the sixth decade). The Takotsubo syndrome cases are mostly preceded by acute emotional or physical triggers such as: family death, financial loss, anxiety, excessive work, domestic abuse, anxiety, fear for medical procedures, severe pain, sepsis, post surgeries, and cancer. Diagnosis of Takotsubo syndrome can sometimes be difficult due to clinical manifestations similar to acute myocardial infarction. Myocardial necrosis biomarkers (Troponin I, Troponin T and Creatinin kinase) are elevated, with values comparable to those in patients with acute myocardial infarction. Transthoracic echocardiography usually shows akinetic or dyskinetic apical and mid-ventricular segments of the left ventricle compared to the hyperkinetic basal segments (“apical ballooning” aspect) and left ventricle systolic dysfunction. The positive diagnosis of Takotsubo syndrome is made on coronary angiography, normal or non-obstructive coronary artery disease

Trends and cardiovascular outcomes of Takotsubo syndrome with cardiogenic shock vs. mixed cardiogenic and septic shock: a nationwide propensity matched analysis

ABSTRACT Introduction Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, can be complicated by shock. The outcomes of patients with TTS complicated with cardiogenic shock (CS) versus mixed cardiogenic and septic shock (MS) is not known. Methods We queried Nationwide Inpatient Sample (NIS) from 2009–2020 to compare TTS patients with CS and MS using International Classification of Disease, Ninth & Tenth Edition, Clinical Modification (ICD- 9 & 10-CM) coding. In-hospital outcomes were compared using one: one propensity score matched (PSM) analysis. The primary outcome was in-hospital mortality. Results Of 23,126 patients with TTS 17,132 (74%) had CS, and 6,269 (26%) had MS. The mean age was 67 years in CS and 66 years in MS, and majority of patients were female (n = 17,775, 77%). On adjusted multivariate analysis, MS patients had higher odds of in-hospital mortality (aOR 1.44, 95% CI 1.36–1.52), AKI (aOR 1.53, 95% CI 1.48–1.58), pressor requirement (aOR 1.37, 95% CI 1.25–1.50). However, had lower odds of MCS use (aOR 0.44, 95% CI 0.40–0.48) and cardiac arrest (aOR: 0.81, 95% CI 0.73–0.90) (p-value <0.0001). Mean LOS and inflation-adjusted hospital charges were higher in MS. Conclusion MS in the setting of TTS have higher rates of in-hospital mortality, AKI, and pressor requirements.

Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats.

The pyrimidine nucleoside uridine and its phosphorylated derivates have been shown to be involved in the systemic regulation of energy and redox balance and promote the regeneration of many tissues, including the myocardium, although the underlying mechanisms are not fully understood. Moreover, rearrangements in mitochondrial structure and function within cardiomyocytes are the predominant signs of myocardial injury. Accordingly, this study aimed to investigate whether uridine could alleviate acute myocardial injury induced by isoprenaline (ISO) exposure, a rat model of stress-induced cardiomyopathy, and to elucidate the mechanisms of its action related to mitochondrial dysfunction. For this purpose, a biochemical analysis of the relevant serum biomarkers and ECG monitoring were performed in combination with transmission electron microscopy and a comprehensive study of cardiac mitochondrial functions. The administration of ISO (150 mg/kg, twice with an interval of 24 h, s.c.) to rats caused myocardial degenerative changes, a sharp increase in the serum cardiospecific markers troponin I and the AST/ALT ratio, and a decline in the ATP level in the left ventricular myocardium. In parallel, alterations in the organization of sarcomeres with focal disorganization of myofibrils, and ultrastructural and morphological defects in mitochondria, including disturbances in the orientation and packing density of crista membranes, were detected. These malfunctions were improved by pretreatment with uridine (30 mg/kg, twice with an interval of 24 h, i.p.). Uridine also led to the normalization of the QT interval. Moreover, uridine effectively inhibited ISO-induced ROS overproduction and lipid peroxidation in rat heart mitochondria. The administration of uridine partially recovered the protein level of the respiratory chain complex V, along with the rates of ATP synthesis and mitochondrial potassium transport, suggesting the activation of the potassium cycle through the mitoKATP channel. Taken together, these results indicate that uridine ameliorates acute ISO-induced myocardial injury and mitochondrial malfunction, which may be due to the activation of mitochondrial potassium recycling and a mild uncoupling leading to decreased ROS generation and oxidative damage.

Cardiovascular complications of chimeric antigen receptor (CAR)-T cell therapy

Abstract Background Mechanisms of cardiotoxicity during chimeric antigen receptor (CAR)-T cell therapy remain unclear to this day, with the main hypotheses revolving around IL-6 mediated myocardial depression during cytokine release syndrome (CRS), stress-induced or takotsubo cardiomyopathy, and direct toxicity from CAR-T cells. Hereby we present the experience of a regional referral centre for CAR-T therapy and the program developed with a dedicated cardio-oncology centre. Purpose To provide preliminary data on cardiovascular-related toxicity of CAR-T therapy in terms of incidence and management. Methods All consecutive candidates for CAR-T therapy were prospectively enrolled since the inception of the CAR-T program in our institution (2021). All patients were refractory to at least two lines of immune chemotherapy and had already undergone anthracycline treatment. After conditioning, all patients were treated with autologous CAR-T cells (tisagenlecleucel, Kymriah). Prior to CAR-T cell therapy, all patients underwent baseline cardiac evaluation at our cardio-oncology facility, including a 12-lead ECG, a complete echocardiogram and cardiac biomarkers. The same routine was performed before discharge, after one month. Supplementary evaluations were performed by an on-call cardio-oncology team according to the attending physicians. Results Eleven patients (6 males, mean age 60±11 years) underwent CAR-T cell infusion. Over the course of follow-up, six patients (54%) experienced CRS after a median follow-up of 12 days (7-40). Two patients with mild symptoms (Grade I) were managed with non-cardiac-related therapy while three Grade 2 patients had to start cardioprotective drugs (ACE-Is and beta-blockers) for transient left ventricular systolic dysfunction (mean lowest LVEF 44.8±3.7%). One patient experienced a Grade IV CRS due to takotsubo syndrome complicated by cardiogenic shock on day 4 and required high-dose vasopressors and mechanical ventilation. Patients experiencing a CRS had similar demographical characteristics and medical history but standard echocardiogram before CAR-T showed a lower baseline LVEF (54.5±5.6% vs 64.6±6.7%; p=.02) and lower baseline right longitudinal systolic function markers (TAPSE: 19±3 vs. 24±4 mm; p=.02 S': .09±.01 vs .13±.02 m/s; p=.03). Cardiac biomarkers (high-sensitivity Troponin I and NT-proBNP) did not show any significant predictive power at baseline. All CRS patients showed a progressive recovery of ventricular function and survived up to one-year of follow-up. Conclusions CAR-T therapy is associated with an increased risk of cardiotoxicity, with up to 36% of all patients requiring unscheduled cardio-oncology evaluation and management both during admission and after discharge. Cardiac adverse events range in degree of severity and should be promptly managed by a dedicated team.

Abstract 17281: Outcome of Stress-Induced Cardiomyopathy in Patients With Covid-19 Infection: A US Cohort Propensity-Matched Study

Introduction: COVID-19 has affected millions of people worldwide and is associated with cardiovascular complications like myocarditis, MI, pericarditis &amp; stress-induced cardiomyopathy (Takotsubo cardiomyopathy). Hypothesis and aim: The aim of our study was to examine the outcomes of stress-induced cardiomyopathy in patients with COVID-19. Methods: Using TriNetX, which aggregates &gt;100 million patients' charts, we identified adults (&gt;18) between Jan. 2020 &amp; Apr. 2023. We identified 2 groups: stress induced cardiomyopathy in the setting of COVID-19, &amp; stress-induced cardiomyopathy without COVID-19. We performed 1:1 propensity score matching for demographics and co-morbidities like DM, HTN, HLD, IHD, CKD, obesity, PVD, COPD, liver cirrhosis, smoking &amp; alcohol abuse. We conducted Kaplan-Meier survival analysis to assess all-cause mortality. Adjusted odds ratios (aOR) with 95% confidence interval (CI) were calculated to express the risk of each outcome. Results: We identified 1990 cases of stress-induced cardiomyopathy with COVID-19, and 27,702 patients with stress-induced cardiomyopathy without COVID-19. The majority were female gender and white race across the groups. Table 1 summarizes the demographics and characteristics of cohorts. After matching, stress-induced cardiomyopathy with COVID-19 were more likely to develop LV thrombus (aOR 1.41 [1.02-1.61]), cerebral infarction (aOR 1.25 [1.05-1.47]), acute respiratory failure (aOR 1.72 [1.53-1.94]), cardiogenic shock (aOR 1.37 [1.09-1.72]), and VTE (aOR 1.86 [1.61-2.14]). No difference was found in VT (aOR 0.89 [0.72-1.10]), or cardiac arrest (aOR [1.13 (0.88-1.45]), figure 1. All cause-mortality was worse in COVID-19 associated stress-induced cardiomyopathy (HR 1.17 [1.007-1.35]). Conclusions: Stress induced cardiomyopathy in the setting of COVID-19 was associated with a higher risk of adverse events and increased mortality compared to stress induced cardiomyopathy without COVID-19.

Abstract 14137: Stress-Induced Cardiomyopathy After Uncomplicated Permanent Pacemaker Implantation

Stress-induced cardiomyopathy (SCMP) after permanent pacemaker (PPM) implantation is rare. Here, we report an additional case which was initially misdiagnosed as another disease due to atypical symptoms after PPM implantation. Case presentation: A 79-year-old woman with dizziness and dyspnea for one month visited Cardiology Department. She had a history of hypertension, dyslipidemia, diabetes-mellitus and stage IV chronic kidney disease. We confirmed complete atrioventricular block. Left ventricular ejection fraction (LVEF) was normal. PPM implantation was successfully performed without complications. The next day she felt very well with no symptoms. On the second day, she suddenly developed a fever and complained severe left neck pain. She had cough, sputum and general weakness without chest pain. C-reactive protein level increased and systolic blood pressure was decreased. We started antibiotics considering infection. We also checked implantation site, but there were no signs of infection. On the third day, echocardiography showed decreased LVEF (30%), akinesia of apical and medium segments of LV wall with preserved kinetics of basal segments without pericardial effusion (Figure 1). There was no significant stenosis on coronary angiography and we confirmed SCMP. After few days, her blood pressure and symptoms were improved. We prescribed sacubitril-valsartan, bisoprolol and furosemide. At 10 days after implantation, she was discharged with improved symptoms. Conclusion: Our case emphasizes that even successful implantation of PPM without complications can be a potential risk of SCMP. In the absence of typical cardiac symptoms after PPM implantation, a poor general condition may also be considered as a sign of SCMP. Therefore, it is necessary to monitor the patient for at least three more days after PPM implantation.

Abstract 17222: Warriors Takotsubo Syndrome

Background: Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy or "broken heart syndrome," is characterized by transient left ventricular dysfunction, typically triggered by negative emotions or physical stressors. It presents with symptoms similar to acute coronary syndrome, but with no associated coronary artery stenosis. “Happy Takotsubo” syndrome, triggered by intense positive emotions, is an uncommon variant and presents a unique challenge in clinical diagnosis. Case Presentation: An 86-year-old woman who was an avid Golden State Warriors fan developed sudden-onset pressure-like chest pain following intense excitement over the Golden State Warriors winning a critical basketball game. In the emergency department, the patient was found to have a high sensitivity troponin greater than 4,000 and ST elevations in leads V3 to V6, meeting STEMI criteria. Emergent cardiac catheterization revealed no coronary artery stenosis. Echocardiography was significant for apical ballooning of the left ventricle, consistent with TTS (Figure 1). Symptoms resolved following low-dose beta-blocker therapy, and the patient was discharged after 24 hours of observation. Repeat echocardiography eleven days later demonstrated near-resolution of the apical ballooning (Figure 2). Discussion: This case highlights "happy Takotsubo" syndrome as a unique presentation of TTS triggered by intense positive emotions. In this case, the patient developed TTS after experiencing excitement over a Golden State Warriors victory. By sharing this case, we aim to contribute to the existing literature and enhance knowledge about this uncommon presentation.

Abstract 18616: When Stress Strikes the Heart: Developing Takotsubo Cardiomyopathy With Uncommon Complications

Introduction: Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy or "broken heart syndrome," is a rare condition that predominantly affects postmenopausal women. The etiology of TCM is not entirely understood, but it is thought to be related to catecholamine-induced myocardial stunning. Clinical presentation typically mimics acute coronary syndrome. Left ventricular outflow tract obstruction (LVOTO) is an uncommon complication of TCM, with only a few cases reported in the literature. Case Presentation: A 78-year-old lady presented with chest pain that started a week ago. It was associated with exertion and resolved with rest. It was located substernally, pressure-like, and was 7/10 in intensity. EKG revealed diffuse inferolateral ST segment depression. Her initial troponin was 0.2 which climbed up to 5. She was diagnosed with NSTEMI and was started on IV heparin. Cardiac catheterization revealed no significant CAD. Echocardiography revealed wall motion abnormalities suggestive of Takutsubo Cardiomyopathy (apical ballooning syndrome) with apical hypokinesis and hypercontractile basal segment of the left ventricle. She also had LVOTO with a peak and mean gradient of 80 and 48 mmHg respectively. Her LVEF was calculated to be 40 %. There also was accompanied systolic anterior motion of the mitral valve leaflet. Given the above findings, she was started on a beta blocker along with an angiotensin receptor blocker. Patient’s chest pain resolved with this and was discharged in a stable condition on day three. Follow up appointment at the clinic showed complete resolution of her HOCM and LVOTO. Discussion: The key to managing patients with TCM is to identify LVOTO early, and avoid inotropes and vasodilators. Beta blockers are seen as the cornerstone of treatment. Fortunately, this is a self-resolving condition and the prognosis is excellent with resolution of echocardiographic abnormalities and symptoms within a few weeks’ time.

Abstract 13013: Predictors of Mortality in Elderly Patients Admitted With Takotsubo Cardiomyopathy and a History of Depression

Introduction: Takotsubo cardiomyopathy(TC) (broken heart syndrome or stress-induced cardiomyopathy) is usually a catecholamine-driven weakening of the left ventricle wall motion due to severe emotional or physical stress. It presents as an acute onset of reversible symptoms resembling acute coronary syndrome without occluded coronary arteries. As emotional stressors often trigger the condition, we aim to evaluate factors that can cause hospital death following admission for TC among elderly patients with depression. Methods: Our study group assessed mortality risk factors in patients ages ≥60 years with a diagnosis of TC and depression from the 2016-2020 National Inpatient Sample. Results: There were a total of 26375 elderly patients who had a diagnosis of TC. Amongst them, 25225 (95.6%) did not survive their hospitalization. After adjusting for variables, we found several factors that increased the odds of all-cause mortality in these patients, such as cirrhosis (aOR 2.093, p&lt;0.01), peripheral vascular disease (PVD)(aOR 1.319, p=0.017), and events of Acute Kidney Injury (AKI)(aOR 3.072, p&lt;0.01). Meanwhile, Females (vs. Males, aOR 0.597, p&lt;0.01), the presence of hypertension(aOR 0.854, p=0.029), lipid disorder (aOR 0.696, p&lt;0.01), smoking (aOR0.74, p&lt;0.01), history of stroke (aOR 0.612, p&lt;0.01) or history of myocardial infarction (aOR 0.536, p&lt;0.01) showed lower odds of mortality among elderly patients admitted with TC. No disparities based on race or insurance forms were observed (Table 1). Conclusions: Our analysis found that patients ages ≥ 60 years with TC had poorer outcomes if they had cirrhosis, PVD, or AKI. While reduced odds of death were seen in females and patients with specific comorbidities such as smoking, hypertension, lipid disorder, history of stroke, or myocardial infarction, further studies, adjusting for the length of diagnosis and the medications being used, should be encouraged to expand and understand our results better.

Abstract 12972: Trained Innate Immunity Through Toll-Like Receptor 4/Interferon Signaling Establishes Cardioprotection in a Stress-Induced Cardiomyopathy Model

Introduction: Although extensively studied, the mechanisms responsible for the development of cardioprotection following preconditioning stimuli are not known. Our group showed that isoproterenol (ISO) mediated cardiac injury induces potent cardioprotection against a second ISO challenge for up to 5 weeks. The lack of an immune response after the second ISO dose and the durability of protection suggested that trained innate immunity might represent a novel mechanism for cardioprotection. Hypothesis: We hypothesized that ISO confers cardioprotection through trained immunity via Toll-like receptor 4 (TLR4) signaling that is activated by damage-associated molecular patterns released by ISO-induced cell necrosis. Methods: Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent (saline), and then 300 mg/kg ISO a week later. Mice were assessed before and after receiving ISO via serum cardiac troponin analysis, flow cytometry, and 2-D echocardiography. Results: The TLR4 agonist lipopolysaccharide (LPS), but not TLR1/2 or TLR3 agonists, induced cardioprotection as shown by decreased troponin I release (p&lt;0.01), reduced cardiac neutrophil influx (p&lt;0.05), and decreased left ventricle wall motion abnormalities (p&lt;0.05) following ISO injury compared to saline treated controls . RNA sequencing identified interferon signaling as commonly upregulated (p&lt;0.05) in mouse hearts a week after LPS or ISO pre-treatment. Blocking type I/II interferon receptors partially abolished LPS-induced cardioprotection, while pre-treatment with recombinant interferon β+γ conferred cardioprotection as shown by decreased troponin I release post-ISO (p&lt;0.01). Given that β-glucan reverses the epigenetic tolerizing effects of LPS in immune cells, we treated mice with β-glucan following LPS pre-treatment and observed that the cardioprotection to ISO was abolished. Conclusions: Viewed together this study shows for the first time that TLR4/interferon signaling confers cardioprotection against ISO-induced injury. Our findings further suggest that this cardioprotective response may be secondary to TLR4 mediated epigenetic changes that dampen immune responses following tissue injury, consistent with trained innate immunity.

Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involved in various processes related to cardiovascular disease. However, the role of Sigmar1 in TTS remains unresolved. In this study, we established a mouse model of TTS using wild-type and Sigmar1 knockout mice to investigate the involvement of Sigmar1 in TTS development. Our results revealed that Sigmar1 knockout exacerbated cardiac dysfunction, with a noticeable decrease in ejection fraction (EF) and fractional shortening (FS) compared to the wild-type model. In terms of the gut microbiome, we observed regulation of Firmicutes and Bacteroidetes ratios; suppression of probiotic Lactobacillus growth; and a rise in pathogenic bacterial species, such as Colidextribacter. Metabolomic and transcriptomic analyses further suggested that Sigmar1 plays a role in regulating tryptophan metabolism and several signaling pathways, including MAPK, HIF-1, calcium signaling, and apoptosis pathways, which may be crucial in TTS pathogenesis. These findings offer valuable insight into the function of Sigmar1 in TTS, and this receptor may represent a promising therapeutic target for TTS.

Early Clinical Outcomes of Patients With Stress-Induced Cardiomyopathy Receiving Acute Mechanical Support in the US

BackgroundThe role of acute mechanical circulatory support (aMCS) in patients with stress-induced cardiomyopathy (SIC) complicated by cardiogenic shock (CS) is not well studied. Here, we describe the incidence and outcomes of aMCS use in SIC-CS using a large national database. MethodsUsing the Nationwide Readmissions Database from January 2016 to November 2019, we identified patients hospitalized with SIC who received isolated intra-aortic balloon pump (IABP), microaxial flow pump (Impella, Abiomed), or extracorporeal membrane oxygenation (ECMO) during the index hospitalization. ResultsA total of 902 among 94,709 hospitalizations for SIC (1.0%) required aMCS during the index hospitalization: 611 had IABP (67.7%), 189 had Impella (21.0%) and 102 had ECMO (11.3%). Patients with ECMO or Impella had higher in-hospital mortality rates than those with IABP (37.3% vs 29.1% vs 18.5%, respectively). There was an increased adjusted risk of in-hospital death with Impella (adjusted odds ratio [aOR], 1.98; 95% CI, 1.12-3.49) and ECMO (aOR, 4.15; 95% CI, 1.85-9.32) vs IABP. Impella was associated with an increased adjusted risk of 30-day readmission compared to IABP (aOR, 2.53; 95% CI, 1.16-5.51). Patients with ECMO or Impella had a higher incidence of renal replacement therapy and vascular/bleeding complications compared to those who received IABP. ConclusionsIn this nationwide analysis using an administrative database, patients who received ECMO and Impella showed higher rates of in-hospital mortality, renal replacement therapy, and vascular/bleeding complications compared to those who received IABP. Patients with more comorbidities may receive more aggressive hemodynamic support which may account for observed mortality differences. Future prospective studies with objective and universal characterization of baseline clinical and hemodynamic characteristics of patients with CS secondary to SIC are needed.

Postoperative opioid-induced respiratory depression or oversedation requiring naloxone treatment in a community hospital: a case series

Background Postoperative opioid-induced respiratory depression and oversedation can lead to fatal events and increase perioperative mortality. In reports from major academic centers, naloxone administration has been used as a proxy for severe opioid overdose. Herein, we studied the incidence, clinical characteristics, and outcomes of postoperative naloxone use in a mid-size community hospital. Methods This was a retrospective review of adult patients who received naloxone within 48 postoperative hours between July 9, 2017, and May 31, 2022. Results During the study timeframe, a total of 23,362 surgical procedures were performed and a total of 19 patients received naloxone (8 in the recovery room, 11 on hospital wards), with an incidence of 8.1 [95% confidence interval 4.9–12.7] per 10,000 anesthetics. In 12 cases (63%), naloxone was indicated for oversedation, and in 7 cases (37%), for opioid-induced respiratory depression. All patients received naloxone within the first 24 postoperative hours. While all patients survived the opioid-related adverse event, 2 patients were intubated, 1 developed stress-induced cardiomyopathy, and 5 required intensive care unit admission. Conclusion The rate of early postoperative opioid-induced respiratory depression or oversedation in our community hospital was low; however, these patients often require a substantial escalation of medical management.