Transient Cardiac Dysfunction Research Articles

Abstract Mo007: Molecular Basis of Sepsis-Induced Cardiomyopathy Under Anthracycline Treatment: Insights from Mouse Model

Anthracyclines constitute a fundamental component in numerous paediatric chemotherapy regimens. However, its myelosuppressive & cardiotoxic nature put patients at risk of sepsis and sepsis-induced cardiomyopathy (SIC). When anthracycline-treated patients develop SIC, successful treatment of sepsis is sufficient for the restoration of cardiac function, giving rise to the 'transient cardiac dysfunction' phenomenon. Although transient it poses compromised clinical outcomes & the mechanism driving this phenomenon remains elusive. We hypothesise that the molecular regulators of the phenomenon lie within cardiac cell populations & is controlled by transcriptional activation. Thus, we aim to model 'transient cardiac dysfunction' in mice and conduct transcriptomics on their heart tissues. ‘Transient cardiac dysfunction’ was modelled in male juvenile C57BL6 mice treated with a cumulative of 10mg/kg doxorubicin followed by sepsis induction via cecal ligation & perforation (CLP) to induce SIC. To recapitulate ‘transient cardiac dysfunction’, antibiotics were administered 20h post-CLP to treat sepsis & restore cardiac function. Controls against doxorubicin (saline treatment) was established. Echocardiography and biological sample curation were conducted at pre-SIC (before CLP), onset-SIC (10h post-CLP) & post-SIC (60h post-CLP). Sepsis was verified based on procalcitonin fold change as compared to pre-SIC (n=3-6). Procalcitonin was 15±1.6 folds higher in dox- (n=3) & 10±0.39 folds higher in saline-treated (n=3) mice at onset-SIC. The infection was more aggressive in dox-treated mice as procalcitonin remained elevated at post-SIC (17.1±2.0, n=4), whereas in saline-treated mice, procalcitonin was reduced by post-SIC (7.9±1.0, n=3). In saline-treated mice, LVEF(%) was reduced at onset-SIC (49.0%±3.0, n=7) from pre-SIC (58.1±1.1, n=7) and recovered to baseline by post-SIC (61.8±1.7, n=5). In the contrary, LVEF in dox-treated mice (n=7) was increased at onset-SIC (62.5±1.7) from pre-SIC (56.0±0.8) & sustained till post-SIC (60.1±1.0), suggesting cardioprotection. Normal distribution was verified before statistical hypothesis testing. In conclusion, ‘transient cardiac dysfunction’ was modelled in saline-treated mice, & novel cardio protective effect was observed in dox-treated mice. Moving forward, longitudinal snRNA-seq will be conducted on whole hearts to identify cardiac cell populations & genes responsible for ‘transient cardiac dysfunction’ & cardioprotection.

Subarachnoid haemorrhage-induced reversible cardiac dysfunction: time course and potential mechanisms.

Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague-Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post-SAH. We determined neuropeptide Y (NPY) 1-5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY-NPY1 receptor pathway, otherwise known as catecholamines.

The Immunology of Takotsubo Syndrome.

Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully treated with anti-inflammatory therapies, supporting the importance of the inflammatory response in TTS. In this article, we provide a comprehensive review of the available clinical and pre-clinical literature on the immune response in TTS, in an effort to not only better understand the pathophysiology of TTS but also to generate insights on the treatment of patients with this disorder.

Doxorubicin Dose Deintensification in Pediatric Osteosarcoma, Is Less Better?

Hadeel HalalshehIntroduction We implemented new clinical practice guidelines (CPG) for patients with osteosarcoma starting in January 2009. These guidelines were based on standard European and American Osteosarcoma Study regimen, which includes six cycles of doxorubicin with a cumulative dose of 450 mg/m 2 . Aiming to reduce cardiac toxicity at our center, we opted to reduce the cumulative dose of doxorubicin to 375 mg/m 2 . Materials and Methods This is a retrospective cohort of osteosarcoma patients aged <18 years, treated at our center between 2009 and 2018. Patients were treated with unified CPG and were prospectively followed. Disease and treatment characteristics were depicted, and survival rates were calculated. When needed, comparison of survival of different groups were conducted using log-rank test. Results After a median follow-up of 43.3 months (range, 2-153 months), 79 patients were diagnosed with osteosarcoma and treated with dose-reduced doxorubicin. Median age at diagnosis was 12.8 years. At diagnosis, 58 patients (73%) had localized disease. The 5-year event-free survival (EFS) for the whole group was 50 ± 5.9%, and overall survival (OS) was 64 ± 5.7%. For patients with extremity nonmetastatic tumors ( N = 56), 5-year EFS and OS were 60 ± 6.9% and 70 ± 6.8%, respectively, and for this group of patients, response to chemotherapy was associated with better EFS ( p = 0.0048) and OS ( p = 0.013). Only two patients suffered transient cardiac dysfunction, which was resolved after treatment. Conclusion Our findings suggest that deintensification of doxorubicin may provide adequate control for pediatric osteosarcoma. In the absence of large randomized clinical trials addressing this issue, developing countries with less resources to treat patients with heart failure may consider using the lower dose.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Pediatric neurogenic stunned myocardium due to blunt head trauma requiring ECMO

We present a case of a child with severe cardiogenic shock due to neurogenic stunned myocardium (NSM) caused by severe traumatic brain injury who was successfully treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). The patient—a healthy 13-year-old boy—presented to the emergency department with a single head injury due to a fall. Computed tomography revealed an acute epidural hematoma. An emergency surgery was planned. However, ventricular fibrillation was detected prior to surgery, and the patient was resuscitated. Postoperatively, severe cardiogenic shock was observed. VA-ECMO was introduced upon NSM diagnosis, and the patient had a good clinical course. NSM is a form of transient cardiac dysfunction associated with acute central nervous system injury and is rare in children. Most cases improve with conservative treatment. However, VA-ECMO may be considered in cases of severe cardiogenic shock. The choice of the site for ECMO cannulation should be carefully considered in pediatric patients.

N-Terminal B Natriuretic Peptide as a Prognostic Marker in Sepsis Induced Myocardial Dysfunction

BACKGROUND: Sepsis-induced myocardial dysfunction (SIMD) is an increasingly recognized form of transient cardiac dysfunction in sepsis patients. AIM: The aim of the study was to evaluation of N-terminal pro brain natriuretic peptide (NT-pro BNP) as a predictor of SIMD and poor outcome in patients with sepsis or septic shock. METHODS: Forty patients were enrolled and divided into: Group 1 with sepsis; Group 2 with septic shock. Each group was subdivided according to the presence or absence of cardiomyopathy. Echocardiography, NT-pro BNP - assay on the 1st and 2nd days of admission - were performed. RESULTS: NT-pro BNP level was significant predictor for cardiomyopathy in all case group with 75% sensitivity, 70% specificity (cutoff level &gt;334 pg/ml) on 1st day of admission and 65% sensitivity, and 80% specificity (cutoff level &gt;325 pg/ml) on 2nd day. On subgroup analysis, pro-BNP had 70% sensitivity, 90% specificity; cutoff level &gt;334 pg/ml for prediction of cardiomyopathy in sepsis group and 70% sensitivity and 80% specificity; cutoff level &gt;357pg/ml in septic shock group. Pro-BNP on 2nd day was excellent predictor of mortality in septic shock group with 100% sensitivity and specificity; cutoff level &gt;350 pg/ml. CONCLUSION: N terminal pro-BNP is a good diagnostic and prognostic indicator for cardiomyopathy and mortality in septic patients.

Recurrent Takotsubo syndrome complicated with ischemic enteritis successfully treated by hydration: a case report

BackgroundTakotsubo syndrome is a sudden and an acute form of transient cardiac dysfunction, triggered by mental and physical stress. The treatment for Takotsubo syndrome is not well understood and is incompletely established. Takotsubo syndrome is partly thought to be caused by coronary ischemia under sympathetic nerve activation.Case presentationWe report the case of an 80-year-old Japanese woman with recurrent Takotsubo syndrome complicated with ischemic enteritis. In this case, abdominal pain and dehydration due to ischemic enteritis is thought to have triggered Takotsubo syndrome. Her life was saved with rapid, adequate intravenous hydration. She was diagnosed with coronary vasospastic angina using coronary angiography on her second admission. This case highlights the potential of adequate intravenous hydration in increasing coronary blood flow. In our case, it should be noted that pulmonary congestion was mild and may have improved Takotsubo syndrome without the use of diuretics.ConclusionAdequate hydration must be considered for prompt improvement of cardiac function in Takotsubo syndrome. Replenishment of fluid to increase coronary blood flow, improvement of heart load without exacerbating heart failure, and stabilization of circulation dynamics can help treat patients with Takotsubo syndrome without using diuretics.

Effect of Anthracycline Dose on Acute Anthracycline Induced Cardiotoxicity in Patients with Acute Myeloid Leukemia Undergoing Hematopoietic Stem Cell Transplantation

Introduction: Whereas the risk of anthracycline-associated chronic cardiomyopathy is associated with a cumulative life time dose of more than 500mg/m2, it is less clear whether anthracycline exposure at lower doses is associated with acute toxicity. Antracyclines are typically given as part of the treatment schedule in newly diagnosed patients with acute myeloid leukemia (AML), and acute toxicity is of particular concern in patients who are candidates for hematopoietic stem cell transplantation (HSCT). In these patients, even transient decrease in cardiac function might affect transplant outcome. However, it is currently unknown whether reduced anthracycline dose causes less cardiac toxicity. Herein we aimed to study the short-term cardiac toxicity associated with anthracycline therapy given during induction in patients with AML who subsequently underwent HSCT.Methods: Single center retrospective analysis of patients with AML who received induction therapy and underwent HSCT. We included all patients with AML who received induction and underwent HSCT for whom echocardiography was available pre- and post- induction therapy. We excluded patients who did not receive anthracyclines during induction. We used the AML ELN 2017 guidelines for risk stratification. The regimen used for induction therapy in most AML patients in our center is “3+7”, which includes daunorubicin at a dose of 60mg/m2/day or 90mg/m2/day on days 1-3, and cytarabine at a dose of 100mg/m2/day on days 1-7.Results: Sixty seven patients that received induction therapy and underwent HSCT between 2007 and 2016 were included in this analysis. The median age at diagnosis was 59 years (range 18-73) and 37 (55%) were males. Most patients had either intermediate (N=28, 42%) or high risk (N=24, 36%) AML. Thirty eight of the patients (56.7%) had de novo leukemia, while the rest of the study population had secondary leukemia. Nineteen patients (29%) received 90mg/m2/day and 42 (63%) received 60/mg/m2/day or an equivalent dose of idarubicin (N=3). Thirty four patients (51%) received salvage chemotherapy, most (N = 29, 43%) with anthracycline-containing regimens.The systolic function was assessed by ejection fraction (EF) and fractional shortening (FS). In 17 patients (26%) the post-induction ejection fraction declined by at least 10%. This change was temporary in 14% (N = 9) and permanent in the remainder. Men were more likely to experience acute reduction in EF (P = 0.02). Conversely, the presence of cardiovascular risk factors did not significantly increase the likelihood of post-induction systolic dysfunction. Likewise, while the post-induction change in FS varied considerably, it was not associated with cardiovascular risk factors. In 18 patients (29.5%) the diastolic function deteriorated. Gender or cardiovascular risk factors were not associated with increased likelihood of developing diastolic dysfunction. Remarkably, patients who developed diastolic dysfunction had improved survival outcome (44.65 compared to 32.9 months, p=0.073), raising the possibility that an increase in diastolic cardiotoxicity is associated with improved efficacy of anthracycline treatment. Similarly, less patients who developed diastolic dysfunction required salvage chemotherapy (53% vs. 42%). On the other hand, patients who developed systolic dysfunction had an inferior survival outcome (Graph1). Higher doses of anthracyclines were associated with a significant decrease in FS (P = 0.043) and a tendency towards EF decline (P = 0.1), however it was not associated with a decrease in diastolic function.Conclusions: Approximately one quarter of patients who receive anthracycline-based induction will develop transient or long-lasting decrease in systolic cardiac function. The anthracycline effect is dose dependent and is higher with a 90mg/m2/day dose than with 60mg/m2/day. The deterioration in cardiac function translated into inferior survival outcome. Recent studies have shown that daunorubicin at a dose of 90mg/m2/day or 60mg/m2/day may have comparable efficacy in the induction regimen for AML. Our data should be taken into account when determining anthracycline dose in this setting, especially in male patients who are candidates for allogeneic transplantation, since even transient cardiac dysfunction might increase transplant-related morbidity and mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Retraction: Transient Cardiac Dysfunction in Cerebrovascular Accidents.

[This retracts the article DOI: 10.7759/cureus.10185.].

The oncological treatment and cardiotoxicity problem – the role of biomarkers

Cancer and cardiovascular diseases are a leading causes of morbidity and mortality in developed countries. Cardiological complications of oncological treatment are a significant problem that can be manifested in both permanent and transient cardiac dysfunction including myocardial damage, left ventricular dysfunction, and heart failure, hypertension, ischemia, as well as arrhythmias or QT prolongation, which can be life-threatening. Early detection of cardiotoxicity due to cancer treatment is crucial in the prevention of adverse cardiovascular outcomes in this group of patients. In this review we try to summarize the role of biomarkers in the detection of cardiotoxicity due to cancer treatment.

Peripartum Heart Failure With Preserved Ejection Fraction: A Distinct But Under-Recognized Clinical Syndrome

Introduction Peripartum cardiomyopathy is a well-described diagnosis characterized by systolic dysfunction. Increasingly recognized is that peripartum women may also develop clinical heart failure with preserved ejection fraction (HFpEF); however, little is known about risk factors, diagnostic criteria, and recurrence. Hypothesis We propose that peripartum HFpEF is an under-recognized entity distinct from peripartum cardiomyopathy and preeclampsia. Peripartum HFpEF may be associated with comorbidities prevalent among other patients with HFpEF and may recur during subsequent pregnancies. Methods We identified pregnant and postpartum patients between 8 weeks antepartum and 7 months postpartum (mean 21 ± 53 days), with symptomatic heart failure and normal ejection fraction (EF) (≥55%) on echocardiogram. Demographics, comorbidities, labs, imaging, treatment, and clinical outcomes were assessed. Outcomes of interest were the association of clinical heart failure with BNP, preeclampsia, and other comorbidities, and long-term outcomes of final EF and subsequent pregnancies. Results Among 44 patients with clinical concern for heart failure, 22 (50%) met clinical diagnostic criteria based on Framingham criteria. Only 2 women (9%) were given a clear diagnosis of HFpEF by providers during their initial presentation. Among patients with HFpEF, 8 (36%) had concomitant preeclampsia. Mean BNP was 208±184 pg/mL, and 4 patients (18%) had BNP below 35 pg/mL. Pulmonary edema was documented in 15 patients (68%). Average non-pregnant BMI was 36.1±7.9 kg/m². Compared with the US adult female population, our cohort had higher prevalence of hypertension (41% vs. 28%), diabetes (36% vs. 12%), and sleep apnea (27% vs. 17%). After 4.7±4.2 years of follow-up, no patients developed systolic dysfunction, 5/22 (23%) women carried an additional term pregnancy, and 1 of those 5 (20%) had recurrent HFpEF during the subsequent pregnancy. Conclusions Peripartum HFpEF is a distinct and under-recognized diagnosis that should be considered in peripartum women with clinical heart failure. Despite clinical symptoms, several women had normal BNP or absent pulmonary edema by chest x-ray, suggesting additional diagnostic criteria may be needed. While preeclampsia is associated with transient cardiac dysfunction, many women with peripartum HFpEF did not have preeclampsia, but did have comorbidities in common with HFpEF. More research is needed to determine longer-term outcomes and risk of recurrence during subsequent pregnancies.

Takotsubo cardiomyopathy in pregnancy: a case report and literature review

BackgroundTakotsubo cardiomyopathy is rare in pregnancy and is characterized by left ventricular dysfunction with apical ballooning. This transient cardiac dysfunction may affect women of childbearing age in the antepartum, intrapartum or postpartum period. Most patients respond well to medical management with resolution of cardiac dysfunction within weeks.Case presentationA 35-year-old female in her second pregnancy presented with severe preeclampsia at 31 weeks of gestation. She subsequently developed severe substernal chest pain and workup showed a stress induced cardiomyopathy prior to her delivery via caesarean section. She had full recovery of her cardiac function by 12 weeks postpartum after medical management.ConclusionsStress induced cardiomyopathy, though rare, should be considered after acute myocardial infarction has been ruled out in gravid females presenting with acute chest pain. Management should involve a multidisciplinary team. Cardiac function recovery is common within 4 weeks although some patients may require long term heart failure management.

Abstract WMP63: New Onset Nonvalvular Paroxysmal Atrial Fibrillation After Acute Ischemic Stroke Without Atrial Cardiopathy- to or Not to Anticoagulant

Introduction: Cardiac outcome in acute ischemic stroke (AIS) remains less well understood as do the neuroanatomic correlates of AIS associated myocardial injury. For patients with new onset paroxysmal atrial fibrillation (Afib), anticoagulant therapy is determined based on the CHA 2 DS 2 -VASc score. However, newly diagnosed short-run Afib after AIS could be neurogenic, without an increase in the risk of AIS recurrence. The present study of 68 patients with acute insular infarcts describes cardiac outcomes including newly diagnosed Afib and clinical significance. Methods and Results: Serial measurements of cardiac troponin I (cTnI), EKG, echocardiography (Echo) (some had transesophageal Echo) were conducted in all patients with MRI-confirmed AIS involving insular cortex. The severity of insular damage was measured with diffusion-weighted imaging. Thirty-one patients (46%) had right MCA infarcts involving insular cortex, and 37 patients had left MCA (54%) stroke with insular involvement. Patients with left MCA infarcts had higher cTnI but did not reach statistical significance. By linear regression analysis in either right or left insular AIS, there was a significant correlation between elevated cTnI and the severity of insular injury. Six patients (3 right and 3 left MCA AISs) were found to have transient cardiac dysfunction. Nine out of 68 AIS patients detected new onset transient Afib in the absence of prior heart disease, cardiac arrhythmia, or evidence of atrial myopathy. Five of them are not on anticoagulant therapy due to varied reasons. None of them experienced recurrent major cardiac events, recurrent Afib, or ischemic stroke during the 12-month follow up. Conclusions: Our study shows that either left or right MCA AIS involving the insular cortex may cause cardiac injury including transient Afib. We further demonstrated a correlation between the severity of insular damage and cardiac sequelae. However, there is no increased risk of recurrent ischemic stroke at 1 year in 5 patients with newly diagnosed Afib not on anticoagulant therapy. A long-term study with large number of AIS patients with newly diagnosed Afib is needed to determine if lifelong anticoagulation is required in this particular group of patients with presumed neurogenic Afib.

Neurogenic stress cardiomyopathy following aneurysmal subarachnoid haemorrhage: a literature review

Summary Neurogenic stress cardiomyopathy (NSC) is defined as transient cardiac dysfunction occurring after primary brain injury, such as aneurysmal subarachnoid haemorrhage, and characterised by left ventricular systolic dysfunction with reduced ejection fraction and abnormalities of regional wall motion. It may also be suspected if elevated levels of cardiac biomarkers and ECG abnormalities are present. It is a reversible condition with favourable long-term prognosis if diagnosed and treated timely, however, NSC is associated with higher rates of early mortality and complications, including pulmonary oedema, cardiogenic shock, delayed cerebral ischaemia. Early diagnosis of the NSC is important in order to prevent these complications and reduce mortality. Management of the NSC is complicated and a multidisciplinary approach is usually required.

Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction.

BackgroundStroke can lead to cardiac dysfunction in patients, but the mechanisms underlying the interaction between the injured brain and the heart are poorly understood. The objective of the study is to investigate the effects of experimental murine stroke on cardiac function and molecular signalling in the heart.Methods and resultsMice were subjected to filament‐induced left middle cerebral artery occlusion for 30 or 60 min or sham surgery and underwent repetitive micro‐echocardiography. Left ventricular contractility was reduced early (24–72 h) but not late (2 months) after brain ischaemia. Cardiac dysfunction was accompanied by a release of high‐sensitive cardiac troponin (hsTNT (ng/ml): d1: 7.0 ± 1.0 vs. 25.0 ± 3.2*; d3: 7.3 ± 1.1 vs. 52.2 ± 16.7*; d14: 5.7 ± 0.8 vs. 5.2 ± 0.3; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); reduced heart weight (heart weight/tibia length ratio: d1: 6.9 ± 0.2 vs. 6.4 ± 0.1*; d3: 6.7 ± 0.2 vs. 5.8 ± 0.1*; d14: 6.7 ± 0.2 vs. 6.4 ± 03; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); resulting from cardiomyocyte atrophy (cardiomyocyte size: d1: 12.8% ± 0.002**; d3: 13.5% ± 0.002**; 14d: 6.3% ± 0.003*; 60 min. MCAO vs. sham; mean ± SEM; **p < 0.01; *p < 0.05), accompanied by increased atrogin‐1 and the E3 ubiquitin ligase murf‐1. Net norepinephrine but not synthesis was increased, suggesting a reduced norepinephrine release or an increase of norepinephrine re‐uptake, resulting in a functional denervation. Transcriptome analysis in cardiac tissue identified the transcription factor peroxisome proliferator‐activated receptor gamma as a potential mediator of stroke‐induced transcriptional dysregulation involved in cardiac atrophy.ConclusionsStroke induces a complex molecular response in the heart muscle with immediate but transient cardiac atrophy and dysfunction.

Transient cardiac dysfunction but elevated cardiac and kidney biomarkers 24\xa0h following an ultra-distance running event in Mexican Tarahumara

BackgroundThe Mexican Tarahumara are accustomed to running ultra-distance races. No data exist on the acute physiological changes following ultra-distance running and physiological-biomarker associations in this population. Thus, we aimed to investigate the acute impact (≤ 24 h) on functional and biochemical changes of the cardiac muscle and biochemical changes associated with kidney function following a 63-km ultra-distance race with an altitude difference of 1800 m in Mexican Tarahumara athletes.MethodsTen Tarahumara male athletes (mean ± SD age = 29.9 ± 6.6 years) volunteered to participate in the study. VO2max was assessed by a sub-maximal step test individually calibrated combining heart rate and accelerometry. Standard transthoracic echocardiography methodology and venipuncture blood tests were carried out at four time points: pre-race, immediately post-race, 6 h, and 24 h post-race.ResultsEstimated mean VO2max was 54.5 (± 8.8) mL O2 min−1 kg−1 and average physiological activity intensity was 746 (± 143) J min−1 kg −1 (~ 11.5 METs). When compared to pre-race values, significant changes in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (− 15%, p < 0.001 for both parameters), cardiac output (39%, p < 0.001), and maximal longitudinal velocity (− 13%, p < 0.009) were seen post-race with LVEF also being decreased at < 6 h post-race (− 8%, p < 0.014). Plasma biomarkers mid-regional pro-atrial natriuretic peptide, copeptin-ultra sensitive, and high-sensitivity cardiac troponin T remained significantly elevated at 24 h post-race, and the two latter were inversely associated with LVEF (p < 0.04). Kidney dysfunction was indicated by increased post-race copeptin-ultra sensitive.ConclusionsThe athletes participating in this study had acute transient cardiac dysfunction as assessed by echocardiography but elevated cardiac and kidney biomarkers at 24 h following a 63-km race with extreme altitude variation.

Frequency of Inverted Electrocardiographic T Waves (Cerebral T Waves) in Patients With Acute Strokes and Their Relation to Left Ventricular Wall Motion Abnormalities

Transient, symmetric, and deep inverted electrocardiogram (ECG) T waves in the setting of stroke, commonly referred to as cerebral T waves, are rare, and the underlying mechanism is unclear. Our study aimed to test the hypothesis that cerebral T waves are associated with transient cardiac dysfunction. This retrospective study included 800 patients admitted with the primary diagnosis of hemorrhagic or ischemic stroke. ECGs were examined for cerebral T waves, defined as T-wave inversion of ≥5 mm depth in ≥4 contiguous precordial leads. Echocardiograms of those meeting these criteria were examined for the presence of left ventricular (LV) wall motion abnormalities. Follow-up evaluation included both ECG and echocardiogram. Of the 800 patients, 17 had cerebral T waves on ECG (2.1%). All 17 patients had ischemic strokes, of which 11 were in the middle cerebral artery distribution (65%), and 2 were cerebellar (12%), whereas the remaining 4 involved other locations. Follow-up ECG showed resolution of the T-wave changes in all 17 patients. Of these patients, 14 (82%) had normal wall motion, and 3 had transient wall motion abnormalities (18%). Two of these patients had Takotsubo-like cardiomyopathy with apical ballooning, and the third had globally reduced LV function. Coronary angiography showed no significant disease to explain the LV dysfunction. In summary, in our cohort of patients with acute stroke, cerebral T waves were rare and occurred only in ischemic stroke. Eighteen percent of patients with cerebral T waves had significant transient wall motion abnormalities. Patients with stroke with cerebral T waves, especially in those with ischemic strokes, should be assessed for cardiac dysfunction.

Takotsubo cardiomyopathy associated with epinephrine use: A systematic review and meta-analysis

BackgroundTakotsubo cardiomyopathy is a syndrome of transient cardiac dysfunction that is frequently associated with sudden emotional or physical stress. Epinephrine use has been implicated in precipitating Takotsubo cardiomyopathy in multiple case reports and case series. We sought to systematically review the current English literature on this association. MethodsWe searched relevant articles on Takotsubo cardiomyopathy associated with epinephrine administration and extracted data on demographic characteristics, clinical features, investigations and clinical outcomes. ResultsWe identified total of 41 cases from 36 articles. The mean age of presentation was (47.07±15.73years) with strong female preponderance (83%, P=0.0001). The most common symptom at presentation was chest pain (82%). Mean peak troponin I level was (7.12±11.22ng/ml). The most common EKG abnormality was ST elevation, seen in 40% of patients. The most common finding on echocardiography was apical hypokinesis, seen in 48.78% cases. Patients younger than 45 were less likely to have apical cardiomyopathy (n=5/20, 25%) compared to patients with age >45 (n=14/21, 66%, p value 0.001, OR 0.17). The most common route of administration of epinephrine was intravenous (65.85%). All patients except one survived with complete recovery of systolic function reported in most cases within an average of 14.7days. ConclusionExposure to epinephrine in clinical practice can trigger Takotsubo cardiomyopathy, which is rapidly reversible with good prognosis in most cases. This review further supports the notion that both exogenous and endogenous catecholamines are associated with the pathogenesis of Takotsubo cardiomyopathy.

Cardiovascular benefits and risks across the physical activity continuum.

Habitual physical activity can reduce the risk of future cardiovascular morbidity and mortality. This review evaluates recent publications that have assessed the impact of the dose of physical (in)activity on cardiovascular outcomes. Sedentary behavior, characterized by prolonged sitting, is increasingly prevalent across the globe and increases the risk for cardiovascular events in a dose-dependent fashion. Similarly, the number of individuals performing endurance exercise events has tripled over the last 2 decades, and some studies suggest that the high volumes of exercise training and competition may attenuate the health benefits of a physically active lifestyle. Breaking up sitting time or replacing sitting by (light) physical activity are effective strategies to attenuate its detrimental health effects. Low doses of physical activity, preferably at a high intensity, significantly reduce the risk for cardiovascular and all-cause mortality. Larger doses of exercise yield larger health benefits. Extreme doses of exercise neither increase nor decrease the risk for adverse outcomes. Athletes demonstrate a transient cardiac dysfunction and biomarker release directly postexercise. Chronic exercise training may increase the risk for atrial fibrillation, but is also associated with a superior life expectancy compared with the general population.