Myocardial Stunning Research Articles

Abstract 4122309: Prognostic implication and hemodynamic characteristics of modified SCAI class in comatose OHCA patients: data from the BOX trial.

Background: Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high mortality. Transient myocardial stunning seen after out-of-hospital cardiac arrest (OHCA) often presents similar clinical characteristics as CS upon hospital arrival. OHCA involves a sudden cessation of circulation followed by a low-flow period during resuscitation, while CS involves prolonged myocardial dysfunction leading to hypoperfusion. The Society for Cardiovascular Angiography and Interventions (SCAI) proposed five distinct shock stages, further refined by the Cardiogenic Shock Working Group (CSWG). OHCA typically places patients in SCAI stage E, but this study abandoned that automatic classification. Methods: This post hoc analysis of the BOX trial data involved comatose OHCA patients with a presumed cardiac cause. Patients were classified using the CSWG-SCAI shock classification upon hospital admission without automatically assigning OHCA patients to stage E. Invasive arterial and pulmonary arterial measurements were taken within the first 72 hours of ICU admission. Cardiac Index (CI), cardiac power output (CPO), and perfusion pressure (mean arterial pressure minus central venous pressure) were calculated. Results: The results demonstrated that 31.6% of the 789 included patients were classified as SCAI class B/C, 29.9% as SCAI class D, and 38.5% as SCAI class E. One-year mortality for SCAI classes was as follows: B/C (21.3%), D (34.3%), and E (48.4%), with a p-value of <0.001 (Figure 1). There was no difference in CI and CPO within the first 72 hours of the ICU stay between SCAI classes. The first recorded perfusion pressure differed between SCAI class B/C and E (63.4±14.3 mmHg vs. 60±14.1 mmHg and 60.9±14.2 mmHg, respectively, p=0.008). This difference was only found at the first measurement. As lactate levels are a variable of SCAI classification, it was anticipated that there would be a significant difference in lactate at arrival. This difference in lactate remained at 36 hours after admission (1.3±0.7 mmol/L vs. 1.6±0.8 mmol/L and 1.9±1.1 mmol/L, respectively, p<0.001), but not thereafter. A higher proportion of patients developed acute kidney injury (AKI) as the SCAI classification increased (20%, 31% and 48%, respectively, p<0.001). Conclusion: One-year mortality increased with increasing SCAI classes but hemodynamic parameters within the first 72 hours of treatment did not differ between groups.

Cardioprotection with transcoronary saline infusion during primary angioplasty for ST-elevation myocardial infarction: design and rationale of the STEMI-Cool pilot study

Abstract Background Prompt restoration of blood flow in ST-segment elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (pPCI) improves outcomes, but is associated with myocardial stunning, increased infarct size, and microvascular dysfunction. To date, there is no effective therapy to reduce this ischaemia-reperfusion injury (IRI). Mild systemic hypothermia has demonstrated potential but is difficult to achieve and poorly tolerated. Transcoronary hypothermia delivers rapid and effective myocardial cooling, is well tolerated, but not effective when commenced after flow restoration. Coronary haemodilution during reperfusion has shown cardioprotective effects in preclinical studies but has not been fully assessed. Purpose STEMI-Cool is a pragmatic, registry-based randomised clinical trial to assess recruitment rate, feasibility, and safety of a simple protocol which we have reported in a proof-of-concept study. The study has commenced recruitment and aims to overcome the limitations of previous negative studies by combining the beneficial effects of transcoronary cooling and dilution, initiating the infusion prior to wire insertion - therefore avoiding initial unprotected reperfusion (likely to be the critical time for IRI), and avoiding significant delays in reperfusion. Moreover, we will explore mechanistic endpoints and an original method to quantify the intracoronary dilution (with a thermodilution-derived "haemodilution constant ratio"). Lastly, we will investigate ways to "engineer out" the thermistor wire so that the method could be applied to routine pPCI with conventional equipment. Methods Pragmatic broad eligibility criteria allow potential recruitment of all STEMI cases clinically eligible for pPCI. Sixty patients will be randomised 1:1 to standard of care or protected reperfusion with continuous infusion of room temperature saline through the guiding catheter, to achieve intracoronary temperature reduction of 6-8°C. The infusion commences prior to crossing the occlusion with a thermistor wire, which is used as guidewire, and continues for 10 minutes after flow restoration (i.e., TIMI flow≥2). Invasive coronary physiology studies are undertaken after pPCI. Novel and established biomarkers of myocardial damage and inflammation (including dipeptidyl peptidase 3, tumor necrosis factor α, and interleukins 1β, 6, 10) are measured in the preprocedural arterial blood. Cardiac imaging and clinical outcomes are assessed at 48h and 6-12 months. Nesting STEMI-Cool in our local registry Heart-ACS facilitates blood sampling and follow-up. Conclusions STEMI-Cool will primarily investigate recruitment rate, feasibility and safety of an innovative, simple cooling and diluting strategy for cardioprotection during pPCI. Mechanistic outcomes will explore inflammatory, microvascular, structural and functional changes. Finally, we will aim to simplify further the protocol for future research and potential clinical use.STEMI-Cool method schematicSTEMI-Cool protocol timeline

Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning.

Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K+) and calcium (Ca2+) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoKATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoKATP channel modulators were evaluated by administering diazoxide (DZX), a mitoKATP opener, and 5-hydroxydecanoate (5-HD), a mitoKATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca2+ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K+ and Ca2+ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoKATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.

Acute myocardial infarction or Takotsubo syndrome in a patient with stunned myocardium due to myocardial bridging? A case report of diagnostic dilemma clarified after serial workup

BackgroundMyocardial bridging is a cardiac anomaly where a segment of epicardial coronary arteries runs through the myocardium and can rarely cause MI. Takotsubo syndrome is a stress-induced cardiomyopathy that can mimic MI. Catecholamine surge during stress can contribute to Takotsubo syndrome, but whether this surge can trigger an inconspicuous myocardial bridging to manifest symptomatically remains unclear, and alternately, whether a myocardial bridge might cause worsening of Takotsubo syndrome is also a matter that needs further research.Case presentationWe report the case of a patient who initially presented with features of acute exacerbation of bronchiectasis and subsequently developed symptoms and ECG features suggestive of acute myocardial infarction. Echocardiography revealed features of takotsubo syndrome, and complete myocardial bridging was revealed via coronary angiography. The patient was managed conservatively with pharmacological treatment, and after a few days, echocardiographic features were reversed. As such, the diagnosis shifted toward Takotsubo syndrome with myocardial stunning due to co-existent myocardial bridging.ConclusionWe report a rare case of a patient with acute bronchiectasis exacerbation with features suggestive of acute myocardial infarction who had findings of Takotsubo syndrome and complete myocardial bridging. In the beginning, it was difficult to determine whether the symptoms arose due to acute MI resulting from myocardial bridging or were solely due to takotsubo syndrome because of stress from bronchiectasis. Although myocardial bridging is often overlooked as an etiology for acute MI, this case highlights the importance of expanding the differential diagnosis to myocardial bridging in the work-up for the cause of acute MI and how Takotsubo syndrome can mimic acute MI and pose a diagnostic challenge.

Metabolomics of repetitive myocardial stunning in chronic multivessel coronary artery stenosis: Effect of non-selective and selective β1-receptor blockers.

Chronic coronary artery stenosis can lead to regional myocardial dysfunction in the absence of myocardial infarction by repetitive stunning, hibernation or both. The molecular mechanisms underlying repetitive stunning-associated myocardial dysfunction are not clear. We used non-targeted metabolomics to elucidate responses to chronically stunned myocardium in a canine model with and without β-adrenergic blockade treatment. After development of left ventricular systolic dysfunction induced by ameroid constrictors on the coronary arteries, animals were randomized to 3months of placebo, metoprolol or carvedilol. We compared these two β-blockers with their different β-adrenergic selectivities on myocardial function, perfusion and metabolic pathways involved in tissue undergoing chronic stunning. Control animals underwent sham surgery. Dysfunction in stunned myocardium was associated with reduced fatty acid oxidation and enhanced ketogenic amino acid metabolism, together with alterations in mitochondrial membrane phospholipid composition. These changes were consistent with impaired mitochondrial function and were linked to reduced nitric oxide and peroxisome proliferator-activated receptor signalling, resulting in a decline in adenosine monophosphate-activated protein kinase. Mitochondrial changes were ameliorated by carvedilol more than metoprolol, and improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. In summary, repetitive myocardial stunning commonly seen in chronic multivessel coronary artery disease is associated with adverse metabolic remodelling linked to mitochondrial dysfunction and specific signalling pathways. These changes are reversed by β-blockers, with the non-selective inhibitor having a more favourable impact. This is the first investigation to demonstrate that β-blockade-associated improvement of ventricular function in chronic myocardial stunning is associated with restoration of mitochondrial function. KEY POINTS: The mechanisms responsible for the metabolic changes associated with repetitive myocardial stunning seen in chronic multivessel coronary artery disease have not been fully investigated. In a canine model of repetitive myocardial stunning, we showed that carvedilol, a non-selective β-receptor blocker, ameliorated adverse metabolic remodelling compared to metoprolol, a selective β1-receptor blocker, by improving nitric oxide synthase and adenosine monophosphate protein kinase function, enhancing calcium/calmodulin-dependent protein kinase, probably increasing hydrogen sulphide, and suppressing cyclic-adenosine monophosphate signalling. Mitochondrial fatty acid oxidation alterations were ameliorated by carvedilol to a larger extent than metoprolol; this improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. Both β-blockers improved the cardiac energy imbalance by reducing metabolites in ketogenic amino acid and nucleotide metabolism. These results elucidated why metabolic remodelling with carvedilol is preferable to metoprolol when treating chronic ischaemic left ventricular systolic dysfunction caused by repetitive myocardial stunning.

#536 Dedicated patient optimization program delivers effective complex intervention improving the lives of vulnerable HD patients

Abstract Background and Aims Hemodialysis (HD) delivery is failing many patients due to a of lack of available evidence/dialysis-based interventions (previously only studied as single interventions in isolation) to improve outcomes; and the industrialization of institutional-based HD imposing a ‘one size fits all’ approach. To respond to the needs of the most vulnerable patients we have instituted a patient optimization program (POP) to support our Renal Program, fully leveraging our research level assessment tools to provide an individualized appreciation of challenges before delivering an equally individualized complex intervention. The aim was to improve subjective experience [symptoms/health related quality of life (HRQoL) measures] and objective evidence of HD related harm. Method Patients who had suboptimal tolerability to HD were identified and referred by the clinical team (after best efforts to address concern as part of standard care). To understand the patients’ individual challenges, a series of physiological, hemodynamic, and HRQoL assessments were completed. Based on these findings, a series of complex foundational (common to all patients treated) and patient specific interventions were applied, and impact rigorously evaluated. HRQoL/symptoms were measured using the dynamic patient reported outcome measurement tool LEVIL [2-4 weeks leading up to the program (baseline) and continually thereafter]. Comprehensive physiological assessment period was two weeks in length (six HD treatments) and included continuous beat to beat hemodynamic monitoring, intradialytic echocardiography (assess myocardial stunning) and objective volume assessment using ultrasound and bioimpedance. The first session was delivered mirroring routine prescription (establish primary response), subsequent treatments were delivered implementing a variety of foundational, patient/disease specific interventions in a staged manner. Results To date 13 patients have completed the program, referred for a variety of reasons [refractory hypotension (5/13), intradialytic hypotension (2/13) and poor HRQoL [symptoms—cramping, headache, pruritus, insomnia (8/13)]. Complexes of challenges were present in 9/13. All patients had multiple components of dialysis altered. POP was associated with a marked improvement in a range of subjective and objective outcomes. Subjectively, HRQoL improved by 10% [composite LEVIL scores 69.5 ± 15.5 at baseline, 76.5 ± 17 after POP participation (p 0.03)], energy by 18% (64.7 ± 16.2, 76.5 ± 6.4, p 0.01), general wellbeing by 11% (76.5 ± 6.6, 85.2 ± 4.2, p 0.02), and post-dialysis recovery improved from 13.3 ± 16.1 hours to only 2 ± 1.9 hours (p 0.02). Objectively, intradialytic weight gain decreased by 36% (2333.3 ± 1151.8 ml at baseline to 1483.3 ± 591.3 ml, p 0.03), systolic blood pressure improved by 12% [94.9 ± 28.5 mmHg at baseline to 106.2 ± 30 mmHg post optimization p < 0.0001 (despite midodrine being discontinued in 8/13 patients previously dependent on it)]. Tolerability of HD improved (cardiac output 6.4 ± 0.1, 6.5 ± 1, p 0.002 and intradialytic systemic vascular resistance response 15 ± 23.6% at baseline to 48.7 ± 53%, p < 0.0001). Improvement in hemodynamic tolerability led to a reduction in HD induced myocardial stunning larger than reported with any previously applied single intervention; regional wall motion abnormality fell from 5.6 ± 2.4 at baseline (severe stunning) to only 1.2 ± 1.3 (p 0.02) over the two-week program. 2/13 patients who had previously been declined transplantation were accepted and need to repatriate from satellite facilities to in-centre was avoided. Conclusion For the first time, we have created an opportunity for the most challenging patients who have failed conventional best efforts. We have successfully demonstrated the impact of delivering a complex intervention (with a degree of treatment personalization) targeting physiological failure in the most vulnerable HD patients. POP improved HRQoL (principal impact measure), hemodynamic stability and treatment tolerability. Having demonstrated the effectiveness of this approach, we now focus on solutions to up-scale this success.

Extracorporeal membrane oxygenation (ECMO) during aplasia: A bridge towards myopericarditis recovery after autologous hematopoietic stem cell transplant for systemic sclerosis and recent Coronarovirus disease (COVID-19) vaccination

Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM).We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered.

Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.

Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function. Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding. IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.

Home Dialysis in Patients with Cardiovascular Diseases.

Kidney failure with replacement therapy and cardiovascular disease are frequently comorbid. In patients with kidney failure with replacement therapy, cardiovascular disease is a major contributor to morbidity and mortality. Conventional thrice-weekly in-center dialysis confers risk factors for cardiovascular disease, including acute hemodynamic fluctuations and rapid shifts in volume and solute concentration. Home hemodialysis and peritoneal dialysis (PD) may offer benefits in attenuation of cardiovascular disease risk factors primarily through improved volume and BP control, reduction (or slowing progression) of left ventricular mass, decreased myocardial stunning, and improved bone and mineral metabolism. Importantly, although trial data are available for several of these risk factors for home hemodialysis, evidence for PD is limited. Among patients with prevalent cardiovascular disease, home hemodialysis and PD may also have potential benefits. PD may offer particular advantages in heart failure given it removes volume directly from the splanchnic circulation, thus offering an efficient method of relieving intravascular congestion. PD also avoids the risk of blood stream infections in patients with cardiac devices or venous wires. We recognize that both home hemodialysis and PD are also associated with potential risks, and these are described in more detail. We conclude with a discussion of barriers to home dialysis and the critical importance of interdisciplinary care models as one component of advancing health equity with respect to home dialysis.

Effect of Intradialytic Exercise on Cardiovascular Outcomes in Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Cardiovascular disease is the leading cause of death among people with kidney failure on hemodialysis, for whom improving cardiovascular health is a research priority. Intradialytic myocardial stunning is common and associated with adverse cardiovascular events. Intradialytic exercise may mitigate intradialytic myocardial stunning and improve cardiovascular structure and function. This systematic review investigated the effect of intradialytic exercise on cardiovascular outcomes in adults undergoing maintenance hemodialysis (PROSPERO #CRD42018103118). Following PRISMA guidelines, we systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, SportDiscus, and PEDro databases from 1960 until June 2022, for randomized and non-randomized studies investigating the effect of intradialytic exercise programs on objective cardiovascular outcomes, pre-specified as primary or secondary outcomes. The primary outcome was arterial resistance. Of 10837 references identified, 32 met eligibility criteria. These studies investigated the effect of intradialytic exercise on arterial resistance (8 studies), blood pressure (20 studies), myocardial structure and function (7 studies), endothelial function (2 studies), sympathetic overactivity (9 studies), biomarkers of cardiac injury (3 studies), cardiovascular hospitalization and mortality (2 studies). Most studies used aerobic exercise as the intervention and usual care (no exercise) controls. Meta-analysis of intradialytic exercise versus usual care resulted in a statistically significant reduction in arterial resistance measured by pulse wave velocity (PWV) with mean difference -1.63 m/sec (95% CI -2.51, -0.75). Meta-analyses for diastolic blood pressure, left ventricular ejection fraction (LVEF), and low-frequency/high-frequency (LF/HF ratio) measure of heart rate variability also showed statistically significant improvements with exercise. There was no significant difference in change in systolic blood pressure, augmentation index, and left ventricular mass index between groups. Intradialytic exercise programming resulted in a clinically meaningful improvement to PWV, a component of arterial resistance. Sseveral physiologic measures of cardiovascular health, including diastolic blood pressure, LVEF and heart rate variability measured by the LF/HF ratio were also observed. The effects of intradialytic exercise on major adverse cardiovascular events remains uncertain.

Takotsubo Syndrome and Coronary Artery Disease: Which Came First-The Chicken or the Egg?

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.

Updates on Prognostication of Takotsubo Cardiomyopathy: A Literature Review

Abstract Takotsubo cardiomyopathy (TTC), commonly known as “broken heart syndrome” or “stress cardiomyopathy,” is characterized by transient left ventricular (LV) systolic dysfunction, usually in the absence of significant obstructive coronary artery stenosis. The pathophysiology of TTC remains elusive; however, the three most common plausible mechanisms include catecholamine surge causing myocardial stunning, multivessel coronary spasm, and microvascular dysfunction. Although initially thought to be a benign, reversible, and transient disorder, newer research data demonstrate that TTC may sometimes have severe short-term complications and some long-term residual effects. Several risk factors have been associated with the outcomes of TTC. In this review, we aim to provide a comprehensive review of the prognostication of TTC in the context of different clinical variables presented in multiple research studies. Various clinical factors, including the types of TTC triggers, the patient’s sex, the presence of cardiogenic shock, atrial arrhythmias, LV tract obstruction, and the presence of certain other clinical comorbidities may significantly impact patient outcomes in TTC patients. A thorough understanding of these factors helps clinicians to better prognosticate the outcome of their patients. Furthermore, early institution of aggressive treatment interventions in the presence of these risk factors may improve the subsequent clinical course.

The spectrum of post-myocardial infarction care: From acute ischemia to heart failure.

Heart failure (HF) is the leading cause of mortality in patients with acute myocardial infarction (AMI), with incidence ranging from 14% to 36% in patients admitted due to AMI. HF post-MI develops due to complex inter-play between macrovascular obstruction, microvascular dysfunction, myocardial stunning and remodeling, inflammation, and neuro-hormonal activation. Cardiogenic shock is an extreme presentation of HF post-MI and is associated with a high mortality. Early revascularization is the only therapy shown to improve survival in patients with cardiogenic shock. Treatment of HF post-MI requires prompt recognition and timely introduction of guideline-directed therapies to improve mortality and morbidity. This article aims to provide an up-to-date review on the incidence and pathogenesis of HF post-MI, current strategies to prevent and treat onset of HF post-MI, promising therapeutic strategies, and knowledge gaps in the field.

Stunned Myocardium as a Sequela of Acute Severe Anemia: An Adult Simulation Case for Anesthesiology Residents.

Anesthesiologists develop anesthetic plans according to the surgical procedure, patient's medical history, and physical exams. Patients with ischemic heart disease are predisposed to intraoperative cardiac complications from surgical blood loss. Unanticipated events can lead to intraoperative complications despite careful anesthesia planning. This anesthetic management simulation was developed for the anesthesiology residency curriculum during the first clinical anesthesia year (CA 1/PGY 2 residents). A total of 23 CA 1 residents participated. A 50-minute encounter focused on a 73-year-old male who presents for an elective total hip replacement and develops acute myocardial stunning in the setting of critical acute blood loss and a delay in the transportation of blood products. One hundred percent of the residents felt the simulation was educationally valuable in the immediate postsimulation survey (Kirkpatrick level 1). The follow-up survey showed that 100% of residents felt the simulation increased their knowledge of managing acute cardiac ischemia (Kirkpatrick level 2), and 93% felt it increased awareness and confidence in similar real-life situations that positively affected patient outcomes (Kirkpatrick level 3). Our simulation provides a psychologically safe environment for anesthesiology residents to develop management skills for acute critical anemia and cardiogenic shock and foster communication skills with a surgery team.

Echocardiographic parameters of the left ventricle in patients after Q-wave and non-Q-wave myocardial infarction

Aim. To perform a dynamic assessment and comparative analysis of non-invasive parameters of myocardial function in patients with Q-wave and non-Q-wave myocardial infarction (MI) during 24-week follow-up after revascularization.Material and methods. A total of 95 patients with acute MI were included. On days 7-9 and after 24 weeks, speckle tracking echocardiography was performed with assessment of global longitudinal (GLS), global circumferential (GCS) and global radial strain (GRS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE).Results. Taking into account the presence/absence of the Q wave, the subjects were divided into two groups: Q-wave MI — 66 patients (69,5%), non-Q-wave MI — 29 (30,5%) people. In the Q-wave MI group, by the 24th week, most parameters of myocardial performance were significantly lower than in the comparison group. In group 1, GWE was 93 (87; 96)% vs 96 (91; 97)% (p=0,04) in group 2; GWI — 1429±444,1 and 1653,3±385,84 mm Hg %, respectively (p=0,02). The GCW level in the Q-wave MI group was 1640±477,8 mm Hg % vs 1852,9±440,88 mm Hg % in the non-Q-wave MI group (p=0,04). Subsequently, a favorable increase in GLS (p=0,01), GWI (p=0,04), GWE (p=0,01), GCW (p=0,03) was revealed in the non-Q-wave MI group.Conclusion. The results obtained suggest that non-invasive parameters of myocardial performance can be used to assess transient ischemic dysfunction due to myocardial stunning, expressed to varying severity in patients with Q-wave MI and non-Q-wave MI.

Temporal proteomic and phosphoproteomic profiling of the left ventricle in a novel rat model of ischemia/reperfusion with or without ischemic preconditioning

Abstract Background The relationship between ischemic preconditioning (IPC) and myocardial stunning is incompletely understood. Preconditioning has been shown to protect against ischemic injury, whereas myocardial stunning, i.e. transient contractile dysfunction in the setting of ischemia, can lead to severe heart failure and has been considered a deleterious process. To understand this relationship, we recently developed a novel rat model of ischemia-reperfusion (I/R) injury in the presence or absence of IPC. In the presence of IPC (2 cycles of 5 min of I/R followed by 13.5 min of ischemia), we observe a profound myocardial stunning at 4h of reperfusion which completely resolves at 48h. In the absence of IPC, we observe necrosis at 4h of reperfusion and sustained injury at 48h. Despite extensive studies on IPC and myocardial stunning in the setting of I/R, the molecular basis of the relationship between these phenomena are still unknown. Purpose To investigate alterations in protein expression after IPC and myocardial stunning in a novel rat model of I/R injury. Methods We utilized tandem mass tags and mass spectrometry to identify temporal changes in the proteomic- and phosphoproteomic-profiles in left ventricular (LV) tissue from rat hearts following 13.5 min of ischemia and 4h of reperfusion in the presence of absence of IPC. Results Proteomics analysis of the LV tissues collected at baseline showed that 115 proteins were differentially expressed between IPC and non-IPC groups. We observed abundant changes in sarcoplasmic proteins, sarcoplasmic reticulum-related proteins, and actin-based cell projection proteins. Most of these proteins are implicated in arylesterase activity, haemoglobin binding, and nitrogen metabolism. At 4h, differentially expressed proteins were predominantly related to wound healing, coagulation, and lipase activity. Phosphoproteomic analysis at baseline showed that 686 phosphosites were differentially regulated between IPC and non-IPC groups. Aberrant phosphorylation patterns mostly occurred in sarcomere proteins, Z-disc, I-band, contractile fiber associated with actin binding, and the thyroid hormone signalling pathway. At 4h, 520 phosphosites differed between IPC and non-IPC rats; these phosphosites were abundant in contractile fiber proteins, myofibril proteins, and sarcomere proteins associated with calcium signalling and cardiomyopathies. Conclusions This study demonstrates marked changes in proteins and phosphosites related to lipase activity, haemoglobin binding, calcium signalling, and the cardiac contractile apparatus in IPC versus non-IPC groups. This extensive catalogue of novel proteins and phosphosites associated with IPC and myocardial stunning in the setting of I/R injury sets the stage for future manipulation of myocardial stunning and preconditioning in both experimental and clinical settings.

Ultrastructural myocardial changes in patients with severe aortic stenosis referred for surgical aortic valve replacement

Abstract Structural myocardial adaptation to pressure overload such as severe aortic stenosis (AS) goes further beyond cardiomyocyte hypertrophy. Progressive fibrosis takes part in left ventricular (LV) remodeling and drives the transition to heart failure. However, the mechanisms underlying this are not fully clarified. Aim To assess ultrastructural myocardial changes occurring in patients with severe AS referred for surgical aortic valve replacement (SAVR). Methods Prospective study of 158 patients (70.9±7.8y, 50%women), with severe symptomatic AS (mean gradient: 60.9±17.4mmHg; valve area: 0.72±0.17cm2; all with high gradient) referred for SAVR with no history of ischemic cardiomyopathy. All patients had complete pre-operative transthoracic echo (LV ejection fraction: 58.9±9.2%; GLS:-14.9±3.7%) and cardiac magnetic resonance with tissue characterization: LV mass index: 80.1±5.9g/m2. Myocardial samples were obtained in 99 patients (62.3%) from intraoperative septal biopsy. Tissue was stained with Verhoeff and Masson´s trichrome for elastic fibers and myocardial fibrosis (MF) assessment, respectively. MF was quantified at an automatic algorithm (QuPath). Inflammation was searched through CD45, CD3, CD20 and CD68 immunostaining. Extracellular matrix (ECM) characterization was performed in 34 samples (alpha-actin, type I collagen, fibronectin and tenascin C immunostaining). Results Mid-wall late gadolinium enhancement was present in 103 patients (65,1%) with a median fraction of 1.9%[IQR 0,1-6,0%] of LV mass. Global LV native T1 and T2 values and extracellular volume fraction were within normal ranges (1057.8±75.4ms, 39.9±4.3ms, 24.7±6.2%, respectively). At histopathology (sample size: 2,446mm [IQR 1,790-3,350mm]) there was cardiomyocyte hypertrophy (median diameter 35mm[IQR 30.2-42.0mm])(Fig, A), variable elastic deposition (elastic endocardium ratio 0.40[IQR 0.2-0.5])(Fig, B), predominant perivascular fibrosis (93.9%) (Fig, C), with a median MF of 13.3% [IQR 7.1-21.0%];57.6% of the patients with dysplastic vessels (Fig, C). Cardiomyocyte enlargement, cytoplasmatic vacuolization and myofiber detachment occurred in 40 cases (40.4%) (Fig, D). This was confirmed as stunning at Periodic acid-Schiff-diastase stain. Inflammation was considered absent in all cases as inflammatory cells were scantily present (median number of CD45+ cells/field: 3[IQR 1.35-6.0]; predominant CD3+). Type I collagen matched MF distribution, following vessel web, such as fibronectin (Fig, E-H). Alpha-actin was detected at the subendocardium in 2/3 of the cases; tenascin C was diffusely positive in 9 cases (27%)(Fig, I). Conclusion These patients with classical severe symptomatic AS were referred for SAVR with diverse ultrastructural myocardial changes. Myocardial stunning occurs in a significant proportion of patients despite the absence of ischemic cardiomyopathy. Inflammation is not involved at this stage of the disease. Distinct grades of ECM remodeling are probably occurring.Figure

Abstract 18676: Aneurysmectomy or No Aneurysmectomy - An Unknown Heart Failure Terrain

Case Report: A 40-year male with a history of traumatic inferoapical ventricular septal rupture after a motor vehicle accident status post patch repair and left ventricular thrombus on Rivaroxaban presented to the ED with hemoptysis. The patient on arrival was hemodynamically stable. CTA revealed a new 6.9 cm left ventricular pseudoaneurysm and an echocardiogram revealed an EF of 30% with a pseudoaneurysm involving the entire distal septum, lateral wall, and apex and a ventricular septal rupture into the intraventricular septum. Cardiac MRI revealed a pseudoaneurysm from the inferoseptal wall measuring 9.6 x 6.9 x 10.0 cm and a stroke volume of 123 mL. A right heart catheterization revealed no evidence of left-to-right shunting. Given heart failure with reduced ejection fraction in the setting of a pseudoaneurysm and the complexity of aneurysm repair, advanced heart failure and cardiothoracic surgery teams were consulted for conventional surgical and transplant evaluation. Due to social barriers, the patient was declined from transplant and ultimately proceeded with patch repair. Intraoperative echocardiography revealed a post-operative EF of 25%. Discussion: This case highlights the need for further data on pseudoaneurysms that are confounded with concurrent heart failure. For this patient, the concerns were for adequate stroke volume given the extent of the pseudoaneurysm and whether improvement in systolic function could be seen with repair or result in further decline. It was postulated that surgical repair would raise his effective stroke volume, and thus improve cardiac function. Postoperative EF changes could have been further explained by myocardial stunning during anesthesia or rapid changes in end-diastolic volume with aneurysmectomy altering Frank-Starling hemodynamics. With isolated case report data, further aneurysmectomy outcome characterization is thus imperative to guide advanced heart failure treatment and improve patient mortality.

Abstract 12525: Acute Pulmonary Edema, Mid-Ventricular Stress Cardiomyopathy and Cardiogenic Shock Following Intranasal Lidocaine/Epinephrine Administration During Septorhinoplasty

Case Presentation: A 19-year-old female presented for elective septorhinoplasty for nasal septal deviation and turbinate hypertrophy. After induction of anesthesia, and orotracheal intubation, pledgets soaked in 4% topical lidocaine with 1:1,000 epinephrine were placed in bilateral nares. Next, 1% lidocaine with 1:100,000 epinephrine was locally injected in the nasal mucosa to obtain hemostasis and analgesia. This resulted in transient hypertensive emergency, followed by undifferentiated shock requiring the initiation of norepinephrine. No signs of ischemia were seen on EKG. Chest X-ray revealed acute pulmonary edema. TTE showed reduced left ventricular systolic function, EF 30%, with mid-segment akinesis, consistent with mid-ventricular stress cardiomyopathy. Coronary angiography identified normal anatomy and patent arteries, supporting the diagnosis. Surveillance TTE after extubation and empiric treatment with metoprolol and losartan, showed improvement of EF to 45-50% and resolution of regional wall motion abnormalities. Discussion: Stress cardiomyopathy, also known as Takotsubo (TCM), is a rare form of cardiomyopathy accounting for 2-3% of ACS. The syndrome mainly affects the LV, causing a regional, transient, systolic dysfunction visualized on TTE or left ventriculography, that occurs in the absence of obstructive epicardial coronary lesions. Pathogenesis is poorly understood. Postulated mechanisms include catecholamine excess, coronary artery spasm and microvascular dysfunction. A systematic review found elevated norepinephrine levels in 74.3% of patients diagnosed with TCM, as was the case for our patient. Rapid systemic absorption of epinephrine can cause diffuse microvascular spasm and myocardial stunning. Catecholamine surge may also afflict direct myocardial toxicity, leading to disorganized cytoskeletal structures, excess extracellular matrix proteins and dysfunctional contractile properties of the myocardium.

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.