Takotsubo Research Articles

Abstract 16945: Aberrant Citric Acid Cycle Metabolites Temporally Coincide With Myocardial Dysfunction in a Rat Model of Stress Cardiomyopathy

Introduction: Stress cardiomyopathy is characterized by transient contractile dysfunction with a poorly understood mechanism. Targeting metabolic derangements has proven efficacious in chronic heart failure, but the role of metabolism in acute cardiac dysfunction is ill-defined. Hypothesis: Characterizing any metabolic alterations in stress cardiomyopathy may help identify potential therapeutic targets. Methods: Sprague-Dawley rats (350 ± 57 g) were given a single intraperitoneal injection of 75 mg/kg isoprenaline. Animals were allocated into groups (N=30 each) based on designated time-points for assessment after injection: control (no injection), day 1, 3, and 7. Rats underwent left ventricular PV loop catheterization followed by harvesting of apical ventricular tissue. Targeted metabolomic analyses were performed via LC-MS and supplemented with enzyme activity assays, qPCR, and Western blotting. Results: Stroke work, cardiac output, and ejection fraction were all significantly reduced by day 1 with recovery by day 7 (Figure A, all p<0.05). Targeted tissue metabolomics revealed peaks in nearly all citric acid cycle metabolites, pyruvate, and lactate that similarly correlated with illness (Figure B). In tandem, anaplerotic amino acids rose with injury while tissue triglycerides decreased. Pyruvate dehydrogenase phosphorylation decreased with decreased expression of pyruvate dehydrogenase kinase (Figure C). However, no differences were noted in tissue acylcarnitine levels despite increased serum fatty acids (all p>0.05). Conclusions: Profound rises in citric acid metabolites with accompanying increases in anaplerotic amino acids are suggestive of metabolic reprogramming in the setting of energetic deficits. Notably, these trends differ from those found in chronic heart failure, and represent a novel phenotypic characterization of stress cardiomyopathy with potential therapeutic implications.

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 16767: Utilization Trends and Sex Disparities in Cardiac Magnetic Resonance Imaging for Cardiovascular Diseases: Insights From TriNetX, a Large Database Analysis

Introduction: Cardiac magnetic resonance imaging (CMR) is an important imaging modality for diagnosing cardiovascular diseases and optimizing therapeutic management. We assessed CMR utilization and potential sex disparities for myocarditis, Takotsubo cardiomyopathy (CM), heart failure, and amyloidosis. Methods: Using the TriNetX database, we conducted a comprehensive analysis, querying adults with diagnoses of these four diseases. CMR risk within 1 year of ICD-10 diagnosis was assessed. Trends in CMR incidence proportion and prevalence between 2015 and 2022 were examined. Odds ratios were used to assess the presence of both sex disparities and temporal differences in CMR utilization for myocarditis in the COVID-19 era. Results: Overall increasing prevalence and incidence proportion of CMR for these four diagnoses are presented in Figure 1. CMR utilization for patients with myocarditis (10.4%), remained consistent between 2019 and 2020. However, the odds of CMR slightly increased in 2021 and then declined in 2022. CMR utilization for Takotsubo, heart failure, and amyloidosis diagnoses was lower, 2.4%, 1.3%, and 4.4%, respectively. Odds ratios revealed higher likelihood of CMR ordered for males than females diagnosed with Takotsubo CM [OR 1.352* (1.143, 1.599)], heart failure [ OR 1.248* (1.221,1.277)], and amyloidosis [OR 1.375* (1.261,1.499)]. Conclusions: Despite CMR's diagnostic and prognostic utility in patients with suspected myocarditis, heart failure, Takotsubo CM, and amyloidosis, CMR utilization is rising but low, with significant sex disparities in referral patterns. Further studies are needed to determine how increased CMR utilization impacts cardiovascular disease diagnosis, patient outcomes, and sex disparities.

Abstract 17123: Opioid Withdrawal Causing a Broken Heart!

Introduction: Takotsubo syndrome is a condition characterized by transient acute left ventricular systolic dysfunction. Although it was previously thought of as a benign self-limiting condition, it is now known to be associated with significant morbidity and mortality. Case: A 26-year-old male patient with past medical history of Fentanyl abuse now on methadone, presented with features of opioid withdrawal. ECG on arrival was normal sinus rhythm with QTc 488 ms. with a troponin of 2.63. Due to excessive agitation and vomiting, he was given IV haloperidol and ondansetron. The patient then became unresponsive and sustained a cardiac arrest. He was found to be in polymorphic ventricular tachycardia and was able to be resuscitated. ECG after resuscitation demonstrated new yamaguchi T waves with a QTc 597 ms and troponin of 6.60. Transthoracic echocardiography subsequently revealed a reduced ejection fraction of 35% with apical hypokinesis, and he was referred for an ischemic evaluation with CTA coronary that showed normal coronary arteries. He was diagnosed with takotsubo cardiomyopathy and was initiated on dapagliflozin, metoprolol succinate and losartan. For opioid dependence, he was prescribed buprenorphine/naloxone being mindful of his QTc and was provided a wearable cardioverter defibrillator on discharge. Final ECG demonstrated QTc of 465 ms. Discussion: Opioid withdrawal is known to cause a high adrenergic state and this catecholamine excess can result in cardiac stunning, creating transient left ventricular dysfunction along with wall motion abnormalities. Patients with takotsubo cardiomyopathy typically have normal coronary arteries. Approximately 4.5% of these patients can die during their hospitalization and 4% can die within 30 days of discharge. So, clinicians must keep a high index of suspicion for this syndrome in patients with history of substance use disorder, especially in the setting of troponin elevation.

Abstract 16856: The Upside Down: A Case of Reverse McConnell’s Sign in Mixed Shock and ARDS

Introduction: We present a case of reverse McConnell’s sign in shock and respiratory failure. Hospital Course: A 48-year-old woman with cirrhosis presented to the emergency department with hypoxia, hypotension, and tachycardia. She endorsed lower extremity edema and orthopnea. Labs noted elevated BNP, procalcitonin, troponin, and lactate. Urinalysis showed signs of infection. EKG did not reveal ischemic changes. CT pulmonary embolism (PE) protocol was negative for PE but showed pulmonary edema. Parasternal short axis views on bedside ultrasound revealed interventricular septal flattening during systole consistent with right ventricular pressure overload ("D sign"). She received broad-spectrum antibiotics for E. coli bacteremia. Trans-thoracic echocardiogram showed a hyperdynamic LV and decreased RV function with a "reverse McConnell sign (rMS)" (figure 1). Providers initiated diuresis once her vasopressor requirement stabilized. She was soon extubated and her oxygen requirement continued to improve with diuresis. Vasopressors weaned in several days. Prior to discharge, trans-thoracic echocardiogram echo showed recovery of RV function. Discussion: This case of respiratory failure and shock highlights the value of prompt echocardiography. Her rMS was likely caused by increased pulmonary arterial pressure from hypoxic vasoconstriction and V/Q mismatch from ARDS. Other heart failure processes seem unlikely. rMS refers to right apical hypokinesis and basal hyperkinesis, inverted compared to its counterpart. Cases are associated with PE and Takotsubo cardiomyopathy, but rMS likely more generally indicates right heart strain. Evidence suggests that rMS may be associated with higher rates of comorbidities and adverse events. Finally, it may represent the RV’s protective mechanism for abruptly increased afterload. Conclusion: Providers should consider rMS as a sign of RV strain to assist diagnosis and management of undifferentiated shock.

Abstract 18707: Concomitant Occurrence of Takotsubo Cardiomyopathy and Posterior Reversible Encephalopathy Syndrome: An Uncommon Encounter With Shared Pathophysiology

CASE PRESENTATION: A 61-year-old African American woman presented in an unconscious state after a seizure. She was febrile, tachycardic, tachypneic alongside elevated lactate, leukocyte counts, and procalcitonin levels. Initial high-sensitivity troponin I was notably raised at 4,217 ng/l, with ekg revealing a new onset left bundle branch block (LBBB). Patient was intubated and needed pressor support. Echocardiogram revealed hypokinesis in the basal-mid left ventricle, with a significantly decreased ejection fraction (EF) of 40%. Chest imaging showed a consolidation in the left lower lobe, and Hemophilus influenzae was identified in the sputum culture. A subsequent lumbar puncture yielded elevated leukocytes and proteins, suggesting a secondary meningitic process. DISCUSSION: She was started on antibiotic therapy for pneumonia and meningitis. LV hypokinesis was thought to be due to Takotsubo cardiomyopathy (TTC) or myocardial infarction. Although uncommon LBBB can be seen in TTC. Her clinical presentation, echocardiogram findings further points her LBBB and troponinemia towards TTC than Myocardial infarction. Patient was managed conservatively. Neuroimaging later on revealed restricted diffusion in bilateral occipital and parietal lobes, consistent with Posterior Reversible Encephalopathy Syndrome (PRES). A delayed coronary angiogram after clinical stabilization ruled out obstructive atherosclerotic disease. Weakness and ataxia improved over the course. EF at discharge was 80%.This case illustrates the possibility of concomitant TTS and PRES, conditions hypothesized to arise following intense physical or emotional stress, in this case, likely triggered by pneumonia and meningitis. This clinical scenario underscores the importance of awareness and understanding of these two entities and their potential for simultaneous presentation, providing valuable insights for clinical decision-making in such complex cases.

Abstract 15237: Feasibility and Diagnostic Accuracy of Handheld Echocardiography in Patients Hospitalized With Acute Coronary Syndrome

Introduction: Transthoracic echocardiography (TTE) is recommended in every acute coronary syndrome (ACS) patient, but is time-consuming and not always deliverable. Development of handheld echocardiography (HHE) devices provide a fast, low-cost method to facilitate rapid bedside clinical assessment of those patients. Hypothesis: We hypothesized that evaluation of hospitalized ACS patients using HHE is feasible and provide similar information to standard TTE in detecting important cardiac pathology. Methods: Patients admitted with ACS were prospectively enrolled, and underwent both bedside HHE (Philips Lumify) and clinical TTE evaluation. Independent analysis of HHE and TTE images was performed by a blinded expert team to determine key predetermined imaging findings that might alter management of ACS patients (Table 1). The TTE analysis was repeated for these variables after 1 month. Agreement of HHE vs TTE was assessed with kappa statistics and compared to agreement of TTE vs TTE as reference standard. Results: The analysis included 108 patients (mean age 65y, 78% male). Duration of HHE was a third faster than targeted clinical TTE (8.2±1.8min vs 12.1±5.0min; p<0.001). Agreement in detecting the following variables was good (>0.60) and similar for HHE vs TTE compared to TTE vs TTE: left ventricle (LV) dilatation, LV hypertrophy, LV ejection fraction <40%, anterior and inferior wall motion abnormalities, right ventricle (RV) dilatation, pericardial effusion, aortic stenosis, ventricle septum defect, and takotsubo cardiomyopathy. Agreement between HHE vs TTE was less good than TTE vs TTE for detection of lateral wall motion abnormalities, RV dysfunction, and LV thrombus. Conclusions: In ACS patients, bedside HHE is faster and provides similar diagnostic information to TTE for the majority of key echo findings. However, important exceptions exist, in particular HHE is less good at detecting lateral wall motion abnormalities, RV dysfunction and LV thrombus.

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 & 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 >100 million patients' charts, we identified adults (>18) between Jan. 2020 & Apr. 2023. We identified 2 groups: stress induced cardiomyopathy in the setting of COVID-19, & 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 & 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 15838: To Tear Again: Recurrent and Complicated Spontaneous Coronary Artery Dissection

Background: SCAD is as an infrequent cause of ACS with a predominance affecting a mean age of 42.6 years and 82% of patients being female. SCAD can be classified as primary or secondary, where primary dissections occur spontaneously, and secondary causes involve the aortic root and are a direct consequence of coronary interventions, surgery, or trauma. Case: 26-year-old female with no previous cardiac or significant family history presented with severe mid-sternal chest pain, radiating to both arms and back, and associated with nausea and cold sweats. Cardiovascular exam was unremarkable. Troponins were elevated at 0.18 and 0.59. Echo showed anteroseptal wall hypokinesis, consistent with Takotsubo cardiomyopathy. ECG showed anterolateral ST elevations. The patient went for cardiac catheterization and had spontaneous dissection of the left main into the LAD/diagonal with 100% occlusion of the LAD and 99% occlusion of the ramus/circumflex. Impella device was implanted due to persistent shock, V. fib., and cardiac arrest. Stents were placed in the proximal, mid, and distal LAD, ramus/circumflex, and LCA. The patient had an LVEF of 25%. Follow-up echo showed an LVEF of 30%, with subsequent Impella removal. Following week, LVEF increased to 45-50%. The patient began aspirin 81 mg, atorvastatin 10 mg, bisoprolol 5 mg, prasugrel 10 mg, and rivaroxaban 10 mg. Over the next few years, she had recurrent chest pain, syncope, palpitations, and a non-viable pregnancy at 12 weeks of gestation due to premature bleeding complications. 3 years after the initial SCAD, the patient presented with spiral dissection of the RCA, requiring three stents. LVEF was 30%. She is being managed with aspirin 81 mg, atorvastatin 20 mg, bisoprolol 10 mg, and prasugrel 10 mg. Discussion: The initial age of presentation of this patient makes this case unique. Risk of recurrent SCAD was present in 17% of patients at a median age of 2.8 years after the initial episode. Triggers for recurrent SCAD include extreme emotional/physical stress and pregnancy. Pregnancy it is not recommended in this patient population. Beta-blockade and adequate BP control are mainstay in medical management and reduce the reoccurrence of SCAD.

Abstract 17623: Estrogen-Mediated Small GTP-Binding Protein GDP Dissociation Stimulator Induction Contributes to Sex Differences in Resilience to Ferroptosis in Takotsubo Syndrome

Introduction: Declining estrogen (E2) has been associated with disproportionate susceptibility to takotsubo syndrome (TTS) in postmenopausal women. Small GTP-binding protein GDP dissociation stimulator (SmgGDS), as a key modulator of cardiovascular disease, plays protective roles in reducing oxidative stress and exerts pleiotropic effects of statins. Whether SmgGDS levels are influenced by E2 status and the effect of SmgGDS on sex differences in TTS are poorly understood. Methods: Clinical data were reviewed from TTS inpatients. Echocardiography, immunofluorescence, and immunohistochemistry were performed together with expression analysis to uncover phenotypic and mechanism changes in sex differences in TTS-like wild-type ( WT ) and SmgGDS +/- mice. HL-1 cardiomyocytes were used to further examine molecular mechanisms. Results: In 14 TTS inpatients, TTS had a higher incidence in postmenopausal women as compared to premenopausal women and men. In murine TTS, female WT mice exhibited higher cardiac SmgGDS levels than male WT mice. Ovariectomy reduced SmgGDS expression in female WT mice, whereas E2 replacement reversed this effect. The physiological importance of this sex-specific E2-mediated SmgGDS response is underscored by the disparity in cardiac adaptation to isoproterenol (ISO) stimulation between both sexes of WT mice. E2-mediated SmgGDS induction conferred female cardioprotection against ferritinophagy-mediated ferroptosis. No such cardioprotection was observed in male WT mice and ovariectomized (OVX) female mice. A causal role for SmgGDS in this sex-specific cardioprotective adaptation was indicated, inasmuch as SmgGDS deficiency abolished E2-modulated cardioprotection against ferritinophagy and aggravated TTS progression in both sexes. Consistently, knockdown of SmgGDS in HL-1 cardiomyocytes exacerbated ferritinophagy and abrogated the protective role of E2 against ferritinophagy. Mechanistically, our findings revealed that SmgGDS deficiency abolished E2-conferred protection against ferritinophagy through activating AMPK/mTOR pathway. Conclusions: These results demonstrate SmgGDS is a central mediator of E2-conferred female cardioprotection against ferritinophagy-mediated ferroptosis in TTS.

Abstract 15960: Mortality Differences Among Myocardial Injury Subtypes in Acute COVID-19, the Omicron Wave Was Different

Introduction: Hospitalization for COVID-19 is often associated with myocardial injury (elevated cardiac troponin [cTn]). In the initial pandemic waves, patients with myocardial injury had increased likelihood of cardiovascular complications and inpatient mortality; however, the differences in impact of distinct subtypes of myocardial injury on mortality is unclear. In addition, little is known about how these outcomes compare with the subsequent, milder, Omicron wave. Methods: Utilizing Mayo Clinic enterprise patients we developed algorithms based on diagnostic/procedural codes, cTn levels, and temporal relationships to positive COVID-19 PCR tests, to determine 5 common subtypes of myocardial injury: stress cardiomyopathy, myocarditis, pericarditis, pulmonary embolism, and myocardial infarction. We examined hospitalized adults with COVID-19; those with elevated cTn designated as cases and others as controls. We fitted Cox models using the following covariates: spline transformed age, sex, race, ethnicity, index date and clinical comorbidities. Patients were analyzed based on admission dates coinciding with either the Alpha-Delta or Omicron waves. Results: Across both wave cohorts, hospitalized patients with acute COVID-19 complicated by myocardial injury had an increased risk of mortality compared to those without ( Figure ). Patients with one of the 5 subtypes examined tended to have higher risk than those in the “other myocardial injury” category. Admission during the Omicron wave, compared to the Alpha-Delta waves, tended to have higher mortality risk in all subtypes except myocarditis. Conclusions: Our algorithms successfully identified subgroups of myocardial injury in patients hospitalized with acute COVID-19 leading to stratification of mortality risk. Surprisingly, among hospitalized patients during the Omicron wave, myocardial injury of most subtypes was tended to have increased risk of mortality compared to the Alpha-Delta waves.

Abstract 11720: Logistic and Economic Burden of Non-Obstructive Hypertrophic Cardiomyopathy - Results From Medical and Pharmacy Claims Data

Introduction: Data are limited on the complication burden of non-obstructive hypertrophic cardiomyopathy (nHCM). Hypothesis: Symptoms and complications increase the logistic and economic burden of nHCM. Aim: To assess pre vs post complication resource use and charges (per person per year [PPPY], in USD) for patients with nHCM. Methods: We used Symphony medical and pharmacy claims data from 2016-2021 to identify (by ICD-10 code) 18,011 adult patients in the United States with symptomatic (SYMP) or asymptomatic (ASYMP) nHCM. SYMP was defined as fatigue, chest pain, syncope, dyspnea, heart failure (HF), or palpitations within 3 months of index date; and complications as atrial fibrillation (AF)/flutter, ventricular fibrillation/tachycardia (VF/VT), supraventricular tachycardia, stress cardiomyopathy, HF, or heart transplant. Results: In SYMP vs ASYMP nHCM (n=9600 vs 8411), mean age was 63±14 vs 62±16 years ( p <0.001), 49% vs 45% were female ( p <0.001), and incidence of complications was 0.96 vs 0.39 per 1000 patient years ( p <0.001; HR 0.44, 95% CI 0.40-0.48). For both groups, the most frequent complications were HF, AF and VT. In SYMP nHCM, complications increased inpatient (IP) admissions ( p <0.001 ) and all-cause charges ($59,070 to $73,630 PPPY; p =0.006), without altering outpatient (OP) visits ( p =0.438) (Fig.). In ASYMP nHCM, complications increased IP admissions, OP visits (both p <0.001), and all-cause charges ($22,711 to $66,053 PPPY; p <0.001) (Fig.). For patients with SYMP vs ASYMP nHCM, incremental post complication charges were $14,560 vs $43,343 PPPY, p =0.007. Conclusions: In this study, patients with SYMP vs ASYMP nHCM were older, predominantly female, and had higher rates of complications. Irrespective of symptoms, complications were associated with increased IP admissions and charges. Our data highlight the value of complication prevention, especially for patients with ASYMP nHCM, for whom complications may steeply increase charges.

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 15188: Mid-Cavity Takotsubo Cardiomyopathy Post CAR T-cell Therapy

Introduction: CAR T-cell therapy has been reported to have cardiovascular (CV) adverse effects mostly in context of cytokine reconstitution syndrome (CRS). Although pathophysiology of CAR T-cell cardiotoxicity (CTCC) is not fully understood, it is thought to be IL-6 mediated which has been implicated as a mediator of myocardial depression in infectious and inflammatory states. Another mechanism is direct cardiotoxicity from potential cross-reactivity with unrelated peptides expressed by normal tissue. We present a case of Takotsubo cardiomyopathy following CAR T cells. Case: 61 year old male with h/o Waldenstrom's macroglobulinemia, DMT2, HLD was admitted for CAR T cell therapy. Following infusion, he developed chills, diaphoresis, tachypnea, tachycardia, chest tightness lasting several hours. EKG had dynamic ST depressions in inferolateral leads with elevated hstroponin (6000 pg/ml). Despite severe pancytopenia, heparin was started for acute coronary syndrome. Pain resolved with morphine and he received tocilizumab for CRS. Echo showed a mid-cavitary variant of Takotsubo involving right and left ventricles with depressed systolic function (LVEF 30-35%; Image). Coronary angiogram was deferred due to bleeding risk. Repeat echo in 2 days showed persistent mid-cavity hypokinesis with slight improvement in LVEF (40%) after initiating beta blocker. The temporal relation of acute mid-cavity dysfunction to CAR T-cells indicates most likely CTCC. Heparin was stopped and he was managed conservatively with plan to reassess LVEF in 2 months. Conclusion: Patients undergoing CAR T-cell therapy should be assessed for CV symptoms using biomarkers and imaging for early detection of cardiotoxicity and prompt initiation of supportive treatment. We present a case of acute mid-cavity left ventricular dysfunction (a Tako-tsubo variant) that was temporally related to CAR T cell infusion. Further studies are needed to determine the frequency of this acute form of CTCC.

Abstract 18669: Pheochromocytoma Crisis Precipitated by Carvedilol

Description of case: Pheochromocytomas are rare, catecholamine-secreting tumors of the adrenal gland. Definitive treatment is surgical, but requires pre-operative optimization with alpha, followed by beta blockade (BB). Initial treatment with BB can precipitate pheochromocytoma crisis, characterized by hemodynamic instability and end-organ dysfunction. This case describes pheochromocytoma crisis in a young, healthy female after switching from metoprolol to carvedilol. A 27-year-old woman is evaluated by an outpatient cardiologist for recurrent palpitations, “hot flashes” and headaches. Mobile telemetry monitor reveals episodes of “SVT” for which she is started on metoprolol succinate. Given her symptoms, testing for plasma free metanephrines is ordered and is markedly abnormal. Subsequently the patient is switched from metoprolol to carvedilol. Within a few hours of taking carvedilol the patient reports sudden onset dyspnea, nausea, vomiting and chest pain. On arrival, vital signs are remarkable for a resting pulse of 130 and blood pressure of 130/97. EKG shows sinus tachycardia. Labs reveal a high-sensitivity troponin of 1,816 ng/L and a 2-hour troponin of 4,560. CT shows a 5.8 cm left adrenal mass. An echocardiogram reveals a reduced LVEF of 45-50% and is suggestive of reverse takotsubo cardiomyopathy. Her carvedilol is discontinued, she is started on prazosin and her symptoms resolve within 24 hours. She later resumes metoprolol and proceeds with surgical excision. Discussion: This case reports a pheochromocytoma crisis likely precipitated by carvedilol and complicated by reverse-takotsubo cardiomyopathy. Interestingly, the patient tolerated metoprolol despite being in the same class. This switch was made knowing she tolerated BB and with the idea that she would benefit from additional alpha-blockade. Carvedilol is a racemic mixture, with S-carvedilol binding beta-1 and -2 receptors while R-carvedilol binds strictly alpha-1. There is evidence that patients catabolize the enantiomers differentially, resulting in higher concentrations of one enantiomer in an unpredictable manner. It is therefore preferred to avoid all BB before sustained alpha blockade while treating pheochromocytoma despite the patient’s previous tolerance.

Abstract 18058: Dorsal Root Ganglion Nerve Block Causing Reverse Takotsubo Cardiomyopathy

A 65-years-old female presents to the emergency room after C2 dorsal root ganglion nerve block for cervicogenic headaches, where intraoperatively she became hypotensive and unresponsive with sinus tachycardia to the 140s. She required brief intubation and intravenous vasopressors for resuscitation and was quickly extubated with complete neurologic recovery within hours of presentation. Her vital signs were within normal limits. She had no clinical signs of heart failure on exam. Laboratory values were within normal limits except for elevated hs- troponin which peaked at 1136ng/L. Her EKG showed nonspecific ST changes and T-wave inversion in the high lateral leads. She underwent transthoracic echocardiogram and was found to have basal to mid inferior wall and inferoseptum akinesis with reduced left ventricular ejection fraction of 35-40%. She was initially asymptomatic, but six hours after presentation developed radiating left arm pain then crushing chest and throat pain, with an uptrend in her troponins to 6539, without dynamic EKG changes. She was urgently taken to the cath lab and was found to have clean coronaries, and ventriculography was performed with findings consistent with reverse takotsubo. She was started on low dose beta blockers and ARBs with complete resolution of symptoms. Reverse takotsubo is a rare variant of takotsubo cardiomyopathy, where basal and midventricular segments of the left ventricle are akinetic, with the majority of patients recovering systolic function within months. This condition is frequently triggered by an intense trigger. To our knowledge, this is the first described case of a high-cervical nerve block precipitating takotsubo.

Takotsubo Cardiomyopathy in the setting of Urosepsis

Takotsubo cardiomyopathy is a rare cardiac condition associated with transient left ventricular apical wall motion abnormalities in association with stress but without any signifcant coronary artery disease. We present a case of takotsubo cardiomyopathy presenting as acute pulmonary edema in the background of urosepsis.

Takotsubo Syndrome: Is It Just a "Broken Heart"?

Takotsubo Syndrome: Is It Just a "Broken Heart"?

Impact of age on the outcomes of Takotsubo syndrome

BackgroundThe impact on age on the short-term and long-term prognosis in patients with Takotsubo syndrome (TTS) is unclear. We aimed to evaluate whether age has prognostic implications during hospital stay and long-term follow-up of TTS patients. Methods688 consecutive patients were admitted for TTS in 7 tertiary centers from January-2008 to June-2021. We divided our cohort into two groups (patients <75 years and ≥75 years). Clinical, analytical, and hemodynamic variables as well as in-hospital management were registered and compared between groups. Mortality rates during hospital stay and follow-up were assessed. Adverse cardiovascular events (ACE) were defined as the composite of cardiovascular death, heart failure event, acute myocardial infarction, stroke and symptomatic arrhythmia. ResultsMedian age was 74.7 years and 49.4 % were ≥75 years. 86.9 % were women and 22.3 % were secondary forms of TTS. In-hospital mortality was 3.6 % (1.5 % cardiovascular). Median clinical follow-up was 4.3 years. Mortality during the follow-up period was 23 % (5.0 % cardiovascular) while ACE were 22.5 %, mainly due to heart failure events. Kaplan-Meier curves showed both higher rates of mortality and ACE in ≥75 years group (30.2 % vs 15.8 %; p < 0.001 and 28.3 % vs 16.7 %; p < 0.001). Age was independently associated with higher rates of overall mortality and ACE in patients with TTS. Hypertension, absence of sinus rhythm, Killip class > I and a more impaired coronary microvascular resistance were also associated to ACE in TTS patients. ConclusionsAdvanced age was associated with higher rate of overall mortality and ACE during long-term follow-up in TTS patients.

The simultaneous occurrence of paraganglioma, Takotsubo syndrome, and Markis type I coronary artery ectasia in the same patient is a rare, high-risk clinical syndrome: a case report

BackgroundPopulation-wide, paraganglioma (PGL) is uncommon. The incidence of Takotsubo syndrome (TTS) ranges from 0.5% to 0.9% and also is an exceedingly rare manifestation of PGL. Coronary artery ectasia (CAE) is also uncommon, with an incidence ranging from 1.2% to 4.9%. Herein, we present a case of PGL, TTS, and Markis type I CAE that occured in the same patient.Case presentationA man in his early 40s was admitted to our hospital with a 16-hour history of abdominal colic. Computed tomography and laboratory examination led to the diagnosis of PGL, coronary angiography led to the diagnosis of Markis type I or Chinese type III CAE, and two echocardiographic examinations led to the diagnosis of TTS. When the patient was treated by phenoxybenzamine instead of surgery for the PGL, his blood pressure and glucose level gradually returned to normal. The CAE was treated by thrombolysis, antiplatelet medications, atorvastatin, and myocardial protection therapies. No symptoms of PGL, CAE, or TTS were seen during a 6-month follow-up, and the patient had an excellent quality of life. We confirmed that phenoxybenzamine was the cause of the TTS because paradoxical systolic motion of the apex, inferior wall, left ventricular anterior wall, and interventricular septum were similarly recovered when the PGL was treated by phenoxybenzamine.ConclusionsTo raise awareness of this illness and prevent misdiagnosis, we have herein presented a case of TTS that was brought on by PGL with Markis type I CAE for clinicians’ reference. In addition, in clinical practice, we should consider the possibility of a concomitant coronary artery disease even if the TTS is caused by a PGL-induced catecholamine surge.