Acute Cardiac Dysfunction Research Articles

SARS-CoV-2-related Multisystem Inflammatory Syndrome in Adults.

Adults infected with SARS-CoV-2 may develop a multisystem inflammatory syndrome (MIS-A) characterized by elevated inflammatory markers and multisystem organ involvement. We report the case of a patient who presented with fever and vomiting at hospital admission. He tested positive for SARS-CoV-2 infection and blood tests showed elevated inflammatory markers. The patient developed acute cardiac dysfunction and shock in less than 24 hours and the echocardiogram revealed an LVEF of 30%. He was discharged 3 weeks later fully recovered. MIS-A should be considered if a compatible syndrome is observed in patients with evidence of SARS-CoV-2 infection by PCR test or serology.LEARNING POINTSMultisystem inflammatory syndrome should be considered in young adults presenting with shock and elevated inflammatory markers.Multisystem inflammatory syndrome may be highly responsive to parenteral steroids.

The Cardio-Hepatic Relation in STEMI.

Background: Hepatic injury secondary to congestive heart failure is well described, however, only limited data exist about the possible impact of acute cardiac dysfunction on the liver. We aimed to explore the possible cardio-hepatic interaction in patients with myocardial infarction. Material and methods: A single-center retrospective cohort study of 1339 ST elevation myocardial infarction (STEMI) patients who underwent primary coronary intervention between June 2012 to June 2019. Echocardiographic examinations were performed to assess left ventricular ejection fraction (LVEF) and central venous pressure (CVP). Patients were stratified into four groups by their LVEF and CVP levels: LVEF ≥ 45%, and CVP ≤ 10 mm/Hg (n = 853), LVEF < 45% with CVP ≤ 10 mm/Hg (n = 364), EF ≥ 45%, with CVP > 10 mm/Hg (n = 61), and LVEF < 45% with CVP > 10 mm/Hg (n = 61). Patients were evaluated for baseline and peak liver enzymes including alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin. Results: Greater severity of cardiac dysfunction was associated with worse elevation of liver enzymes. We found a graded increase in mean levels of maximal ALT, first and maximal ALP, and first and maximal GGT values. Using propensity score matching to estimate the impact of cardiac dysfunction on liver injury, we chose patients with the worst cardiac function parameters: (LVEF < 45% and CVP >10 mm/Hg; n = 61) and compared them to matched patients with better cardiac function (n = 45). We found a significantly higher level of maximal ALT, first and maximal ALP, and GGT values in the group with the worst cardiac function parameters (p < 0.05). Conclusions: Among patients with STEMI, the combination of decreased LVEF and venous congestion was associated with liver enzymes elevation suggesting a possible cardio-hepatic syndrome.

AT1 receptor blocker inhibits HMGB1 expression in pressure overload-induced acute cardiac dysfunction by suppressing the MAPK/NF-κB signaling pathway

ABSTRACT Background High-mobility group box 1 (HMGB1) expression not only peaks during the early phase of pressure overload (PO), but also serves a role in the pathogenesis of PO-induced cardiac remodeling. Meanwhile, angiotensin II type 1 (AT1) receptor blockers reverse PO-induced cardiac remodeling and repress the secretion of inflammatory factors. However, whether AT1 receptor inhibitors decrease HMGB1 expression in the early stages of PO remains unknown. Materials and methods PO mouse models were established using transverse aortic constriction (TAC), in which losartan was administrated. Transthoracic echocardiography was performed 3 days after the operation, and serum and cardiac HMGB1 expression, as well as the expression levels of related proteins were measured. Results PO-induced acute cardiac dysfunction was observed 3 days after TAC, and was subsequently slightly, but not significantly relieved by losartan. The expression levels of HMGB1, tumor necrosis factor-α and interleukin-6 in both the serum and myocardium were upregulated in response to TAC, while they were significantly reduced by losartan. Moreover, the phosphorylation of extracellular signal-regulated kinases, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in the myocardium were significantly increased under PO, and this was also prevented by losartan. Conclusion These data suggest that losartan may downregulate the expression of HMGB1 in acute cardiac dysfunction induced by PO by inhibiting the MAPKs/NF-κB signaling pathway, which indicates a novel beneficial role of AT1 receptor antagonists in ameliorating cardiac remodeling under PO.

Clothes dryer–induced heat stroke in three cats

To describe the clinical course of 3 cats successfully treated following clothes dryer-induced heat stroke. Three cats were treated after accidental clothes dryer-induced heat stroke. All cats fulfilled canine heat stroke criteria and showed evidence of heat injury, including neurological dysfunction, corneal and mucosal ulceration, and evidence of rhabdomyolysis. Coagulopathy, acute liver injury, acute kidney injury, cardiac dysfunction, and gastrointestinal signs were seen in cats with a longer duration of dryer exposure. Describes the management of cats after inadvertent clothes dryer-induced heat stroke.

Multimodality Imaging of the Brain-Heart-Axis after Ischemic Stroke Reveals Acute and Chronic Cardiac Dysfunction after Cerebral Ischemia

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG; Ev Studienwerk Villigst Introduction Cerebral ischemia remains a major contributor to global morbidity and mortality. Beyond neurological dysfunction, cerebral stroke also increases risk of subsequent cardiac events and development of chronic heart failure. The mechanisms underlying this brain-heart communication are poorly characterized, but systemic inflammation is thought to play a role. Purpose We hypothesized that cerebral ischemic stroke evokes systemic inflammation contributing to acute cardiac stress and persistent contractile dysfunction, which may be monitored by serial molecular imaging by positron emission tomography (PET). Methods C57Bl6 mice underwent transient (30min) intraluminal middle cerebral artery occlusion (MCAo, n = 88) to induce stroke or sham surgery (n = 18). Serial 18F-GE180 PET at 24h, 7d, and 21d after injury identified translocator protein (TSPO) in brain microglia and peripheral macrophages as a marker of inflammation. Magnetic resonance imaging (MRI) determined stroke size and characterized cardiac function at 1 and 3wk after MCAo. Imaging signals were confirmed by autoradiography, immunohistochemistry and fluorescence-activated cell sorting. Results MCAo in mice induced cerebral stroke of variable size (median 44.68mm3, range:5.12-139.60mm3). Localized inflammation in the injured hemisphere was observed by TSPO PET covering territory consistent to the stroke location, with marked increase in the neuroinflammatory signal at 7d relative to the contralateral hemisphere (% injected dose (ID)/g max: 3.82 ± 0.84 vs 2.51 ± 0.32, p &amp;lt; 0.001). TSPO signal was similarly elevated in the stroke region compared to sham animals (%ID/g max: 3.82 ± 0.84 vs 2.59 ± 0.72, p &amp;lt; 0.001). Corresponding with neuroinflammation, a heightened global myocardial TSPO signal was observed 7d after MCAo compared to sham (%ID/g: 7.75 ± 2.79 vs 5.61 ± 1.98, p = 0.041). TSPO PET signal remained elevated 21d after stroke in brain (3.20 ± 1.15 vs 2.46 ± 0.37, p = 0.012) and heart (8.62 ± 2.43 vs 5.85 ± 0.66, p = 0.022). Cerebral stroke was associated with reduced contractile function compared to sham at 1wk (ejection fraction, EF: 49.58 ± 16.90 vs 62.17 ± 5.25%, p = 0.025) and 3wk (54.30 ± 5.70 vs 66.06 ± 3.48%, p = 0.009). Larger stroke size identified early after injury by T2 weighted MRI, reflecting the focal injury and penumbra edema, correlated with worse subsequent cardiac function at 21d (r = 0.745, p = 0.009). Despite increased TSPO signal, flow cytometry showed comparable CD45+ leukocyte content in the left ventricle after MCAo compared to sham at 7d (p = 0.749). Conclusions Ischemic stroke evoked parallel cerebral and cardiac TSPO upregulation and persistent contractile dysfunction, beginning early after injury. The extent and severity of brain injury predicts left ventricle dysfunction, but the role of inflammation requires further investigation. Molecular imaging may identify risk and guide novel therapies to improve cardiac outcome after stroke.

Management of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Infection.

Purpose of reviewThe purpose of this review is to summarize what is known about multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.Recent findingsThe timing of presentation and features of diagnosis are described. Cardiac involvement is common and is the focus of this review. Arrhythmias, heart block, acute heart failure, shock, cardiac dysfunction, and coronary dilation have all been reported. Therapies used to treat children with this hyperinflammation syndrome include supportive care and agents that modulate the immune system. Therapies commonly described include intravenous immunoglobulin, steroids, and cytokine-directed agents, particularly tumor necrosis factor-alpha blockade and interleukin receptor blockade. The threshold for diagnosing coronary involvement in MIS-C is coronary artery dimensions indexed to body surface that exceed the normative values (Z score >2). Those hospitalized with MIS-C are evaluated by electrocardiogram and echocardiogram; outpatient assessment by a cardiologist is indicated prior to sports clearance.SummaryThe prognosis of treated MIS-C patients is good. Future work is needed to understand the scope of cardiac involvement associated with acute COVID-19 and MIS-C in children and to define the optimal therapeutic targets for these distinct entities.

Cardiac performance in patients hospitalized with COVID-19: a 6month follow-up study.

AimsMyocardial injury is frequently observed in patients hospitalized with coronavirus disease 2019 (COVID‐19) pneumonia. Different cardiac abnormalities have been reported during the acute COVID‐19 phase, ranging from infra‐clinic elevations of myocardial necrosis biomarkers to acute cardiac dysfunction and myocarditis. There is limited information on late cardiac sequelae in patients who have recovered from acute COVID‐19 illness. We aimed to document the presence and quantify the extent of myocardial functional alterations in patients hospitalized 6 months earlier for COVID‐19 infection.Methods and resultsWe conducted a prospective echocardiographic evaluation of 48 patients (mean age 58 ± 13 years, 69% male) hospitalized 6 ± 1 month earlier for a laboratory‐confirmed and symptomatic COVID‐19. Thirty‐two (66.6%) had pre‐existing cardiovascular risks factors (systemic hypertension, diabetes, or dyslipidaemia), and three patients (6.2%) had a known prior myocardial infarction. Sixteen patients (33.3%) experienced myocardial injury during the index COVID‐19 hospitalization as identified by a rise in cardiac troponin levels. Six months later, 60.4% of patients still reported clinical symptoms including exercise dyspnoea for 56%. Echocardiographic measurements under resting conditions were not different between patients with versus without myocardial injury during the acute COVID‐19 phase. In contrast, low‐level exercise (25W for 3 min) induced a significant increase in the average E/e′ ratio (10.1 ± 4.3 vs. 7.3 ± 11.5, P = 0.01) and the systolic pulmonary artery pressure (33.4 ± 7.8 vs. 25.6 ± 5.3 mmHg, P = 0.02) in patients with myocardial injury during the acute COVID‐19 phase. Sensitivity analyses showed that these alterations of left ventricular diastolic markers were observed regardless of whether of cardiovascular risk factors or established cardiac diseases indicating SARS‐CoV‐2 infection as a primary cause.ConclusionsSix months after the acute COVID‐19 phase, significant cardiac diastolic abnormalities are observed in patients who experienced myocardial injury but not in patients without cardiac involvement.

A Randomized Porcine Study in Low Cardiac Output of Vasoactive and Inotropic Drug Effects on the Gastrointestinal Tract.

ABSTRACTBackground:Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO.Methods:In anesthetized pigs, CO was lowered to 60% of baseline by partial inferior caval vein balloon inflation. The animals were randomized to placebo (n = 8), levosimendan (24 μg kg−1 bolus, 0.2 μg kg−1 min−1, n = 7), milrinone (50 μg kg−1 bolus, 0.5 μg kg−1 min−1, n = 7), vasopressin (0.001, 0.002 and 0.006 U kg−1 min−1, 1 h each, n = 7) or norepinephrine (0.04, 0.12, and 0.36 μg kg−1 min−1, 1 h each, n = 7). Hemodynamic variables including mesenteric blood flow were collected. Systemic, mixed-venous, mesenteric-venous, and intraperitoneal metabolites were analyzed.Results:Cardiac output was stable at 60% in all groups, which resulted in systemic hypotension, low superior mesenteric artery blood flow, lactic acidosis, and increased intraperitoneal concentrations of lactate. Levosimendan and milrinone did not change any circulatory variables, but levosimendan increased blood lactate concentrations. Vasopressin and norepinephrine increased systemic and mesenteric vascular resistances at the highest dose. Vasopressin increased mesenteric resistance more than systemic, and the intraperitoneal lactate concentration and lactate/pyruvate ratio.Conclusion:Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High-dose vasopressors may have side effects in the splanchnic circulation.

Abstract 15919: Latent Trajectory Patterns of Left Ventricle Ejection Fraction Among Heart Failure Patients With Chronic Inflammatory Disease: Longitudinal Analysis of Electronic Health Records

Background: Immune regulation and inflammation play a role in the pathogenesis and progression of acute and chronic heart failure (HF). While overt inflammatory cardiomyopathy is a well-described clinical entity marked by acute cardiac dysfunction and relatively high rates of recovery, trajectories in cardiac function among people with chronically heightened systemic inflammation are less clear. We hypothesized that there are differences in trajectories of left ventricular ejection fraction among HF patients with different chronic inflammatory diseases (CIDs): human immunodeficiency virus (HIV), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. Methods: We analyzed serial echocardiographic data from people with CIDs and HF who had at least three echocardiograms (n=974) at a large academic medical center. We identified latent trajectories patterns of LVEF using latent class trajectory models, then described clinical differences across the different trajectories. We then used multinomial regression to test if CID type and other baseline variables were associated with different trajectories. Results: We observed three major LVEF trajectories which paralleled known HF subtypes: preserved/intermediate EF (HFp/iEF, 687, 70.5%), reduced EF (HFrEF, 255, 26.2%), and recovered EF (HFrecEF, 32, 3.3%). These trajectories corresponded closely to accepted clinical definitions. For example, 30/32 (94%) patients in the HFrecEF trajectory had LVEF &lt;40% at baseline that increased ≥15% on ≥1 follow-up. We observed significant differences in associations of CID type, age, sex, and diabetes with a specific LVEF trajectory (Figure) that remained even after regression. Conclusions: Among people with HF and CIDs, different trajectories of LVEF are associated with different CIDs and clinical characteristics. This may have implications for therapy and prognosis of HF in CIDs.

Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study

ObjectiveTo describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. MethodMulticenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. ResultsFifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4−10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. d-Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5–6.5). The median length of PICU stay was six days (IQR 5–11), and one death occurred (1.8%). ConclusionsMost characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

Role of angiotensin-converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection.

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by preexisting cardiovascular disease. Disruption of homeostatic mechanisms secondary to pulmonary pathology ranks high on the list, and there is growing evidence that direct infection of cardiac cells can occur. Angiotensin-converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang-(1–7) but also elicits a beneficial response profile counteracting that of Ang II. Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. Given the important roles that pericytes have in the microvasculature, infection of these cells could compromise myocardial supply to meet metabolic demand. Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.

A young adult with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)-like illness: a case report

BackgroundA healthy 25-year-old woman developed COVID-19 disease with clinical characteristics resembling Multisystem Inflammatory Syndrome in Children (MIS-C), a rare form of COVID-19 described primarily in children under 21 years of age.Case presentationThe patient presented with 1 week of weakness, dyspnea, and low-grade fevers, followed by mild cough, sore throat, vomiting, diarrhea, and lymph node swelling. She was otherwise healthy, with no prior medical history. Her hospital course was notable for profound acute kidney injury, leukocytosis, hypotension, and cardiac dysfunction requiring ICU admission and vasopressor support. MIS-C-like illness secondary to COVID-19 was suspected due to physical exam findings of conjunctivitis, mucositis, and shock. She improved following IVIG, aspirin, and supportive care, and was discharged on hospital day 5.ConclusionMIS-C-like illness should be considered in adults presenting with atypical clinical findings and concern for COVID-19. Further research is needed to support the role of IVIG and aspirin in this patient population.

New insights into the pathophysiological mechanisms underlying cardiorenal syndrome.

Communication between the heart and kidney occurs through various bidirectional pathways. The heart maintains continuous blood flow through the kidney while the kidney regulates blood volume thereby allowing the heart to pump effectively. Cardiorenal syndrome (CRS) is a pathologic condition in which acute or chronic dysfunction of the heart or kidney induces acute or chronic dysfunction of the other organ. CRS type 3 (CRS-3) is defined as acute kidney injury (AKI)-mediated cardiac dysfunction. AKI is common among critically ill patients and correlates with increased mortality and morbidity. Acute cardiac dysfunction has been observed in over 50% of patients with severe AKI and results in poorer clinical outcomes than heart or renal dysfunction alone. In this review, we describe the pathophysiological mechanisms responsible for AKI-induced cardiac dysfunction. Additionally, we discuss current approaches in the management of patients with CRS-3 and the development of targeted therapeutics. Finally, we summarize current challenges in diagnosing mild cardiac dysfunction following AKI and in understanding CRS-3 etiology.

Cardiac troponin elevation in patients with influenza virus infections

The association between acute infections and cardiac injury, including myocarditis and acute myocardial infarction, is now well established. We have performed a systematic literature review for analyzing the results of epidemiological studies that measured cardiac troponins (cTn) in patients with Influenza virus infections. Overall, 14 articles were finally identified and analyzed. Taken together, the results of the scientific literature suggest that cTn elevation is a relatively rare phenomenon in patients with Influenza virus infection, with frequency generally comprised between 0 and 33%, more likely in elderly patients with significant comorbidities. In patients with modest cTn elevations, this phenomenon is apparently self-limited, transient and reversible, and especially involves patients with Influenza A (especially H1N1). In the minority of patients exhibiting an abrupt appearance of cardiovascular symptoms and concomitant elevation of cTn values, the relative increase of this biomarker reflects the presence of an underlying cardiac injury, that can be either myocarditis or an acute ischemic episode. Enhanced cTn values can also be more frequently observed in Influenza patients with complicated disease, in those developing acute respiratory distress syndrome and cardiac dysfunction, as well as in those at higher risk of death. cTn measurement shall be considered a valuable option in all patients developing acute cardiovascular symptoms during Influenza virus infections, as well as in those bearing cardiac or extra-cardiac comorbidities who bear a higher risk of complications.

Fingolimod Attenuates Lung Injury and Cardiac Dysfunction after Traumatic Brain Injury.

Acute lung injury (ALI) and cardiac dysfunction are common in traumatic brain injury (TBI) patients and always indicate poor outcomes. Inflammatory responses play important roles in TBI-induced cardiac and pulmonary damage. Fingolimod, an immunomodulatory agent, alleviates brain edema, restores the integrity of the blood-brain barrier (BBB), and improves functional deficits by inhibiting multiple inflammatory responses. Fingolimod (1 mg/kg) was injected intraperitoneally at 2 h after the controlled cortical impact (CCI) model was established in adult male mice. The concentration of inflammatory cytokines in the lung and heart after TBI was measured with a cytokine array. The lung wet/dry weight ratio and Evans blue dye leakage were used to quantify pulmonary edema and capillary leakage. Immunofluorescence, electron microscopy, and echocardiographic examination were used to assess the pathology and functional deficits in hearts. We found that TBI caused significant heart and lung damage. The administration of fingolimod significantly reduced the elevated inflammatory cytokine production, neutrophil infiltration, the leakage of protein in bronchoalveolar lavage fluid (BALF), and the wet/dry weight ratio in lung tissue at 3 days after TBI. In addition, fingolimod treatment also alleviated the inflammatory response in the heart; decreased cardiac apoptosis, fibrosis, and histological microstructural changes; and improved cardiac function from 3 days after TBI and maintained it for 30 days after TBI as measured by echocardiography. These results suggest that TBI resulted in significant cardiac and pulmonary damage accompanied by significant inflammatory responses in heart and lung tissue. Fingolimod treatment reduced the inflammatory response and alleviated TBI-induced lung and heart injury.

P1707SIMULTANEOUS HEART-KIDNEY TRANSPLANT: OUR 10 YEARS' EXPERIENCE

Abstract Background and Aims The number of patients listed and receiving simultaneous heart-kidney transplantation (SHKT) has significantly increased in the last decade. This is likely due to the increased knowledge that SHKT is associated with a significant survival benefit in patients with heart failure with chronic kidney disease (CKD), compared to isolated heart transplant and sequential heart and kidney transplantation. Recent analysis of large data bases has shown a survival benefit in SHKT even in older patients and beyond dialysis dependent patients. However, this benefit is only proven for irreversible CKD which is often difficult to prove in patients with severe heart failure. Our center has the largest experience in SHKT in Portugal, and our aim is to report our experience with a total of 8 recipients and their outcomes after 10 years of follow up. Method We performed a retrospective analysis of all the patients submitted to SHKT in Coimbra University Hospital Center from 1 January 2009 to 31 December 2019. Data was collected using the clinical and laboratorial registries from our database. Follow up at December 2019 varied between 6 months to 10 years (median 5,5 years). Results A total of 8 patients received SHKT between 1 January 2009 and 31 December 2019. Only one patient was female and the mean age at transplant was 58.88 ± 9.7 years. The etiology of heart failure was dilated cardiomyopathy (N=4, 50%), severe valvular disease (N=2, 25%), ischemic cardiomyopathy (N=1, 12,5%) and one patient had familiar amyloidosis (N=1, 12,5%). Regarding CKD, the majority of the patients had type 2 cardiorenal syndrome (N=5, 62,5%), one patient had calcineurin toxicity due to previous liver transplantation, one patient had autosomal dominant polycystic disease, and in one patient the etiology remained unknown. Half of the patients were on chronic hemodialysis program for more than 3 months, and the remaining were preemptive. Regarding post-transplant results, average hospitalization was 19 days. Seven patients (87,5%) had immediate cardiac graft function (mean LVEF 70 ± 5.8% and mean PSAP 22.25 ± 5.6 mmHg). One patient had acute cardiac and subsequent renal graft dysfunction and died during hospitalization. Regarding renal graft outcomes, besides the patient that died, another patient had primary renal graft dysfunction due to renal artery thrombosis and one patient presented late graft function. The remaining five patients had immediate graft function and presented normal kidney graft function at follow up. Regarding complications, neoplasia was reported in two patients (one with sarcoma and the other with prostatic cancer), and there were twenty-five episodes of infection, present in all patients. Mortality at follow up was 37% (N=3). One of these, described above, died during hospitalization twenty-two days after transplant, and the other two died 4 and 5 years later due to a cardiovascular event and sarcoma, respectively. At follow up in 2019 five patients present stable kidney graft, good cardiac function and no recent complications. Conclusion In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation might be the best approach and appears to be associated with better graft and patient survival. Despite having a small number of cases, our center has the biggest experience in SHKT in Portugal and our results are very satisfying. A multidisciplinary approach between Nephrology, Cardiology and Cardiothoracic Surgery is fundamental and in the next decades it is expected an increase in SHKT number.

Role of PI3K/AKT/mTOR Pathway Associated Oxidative Stress and Cardiac Dysfunction in Takotsubo Syndrome.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, but the accurate cause of this syndrome is still unknown. β-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infect with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt) and then, treated with ISO. Cell apoptosis was assessed using the Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE). Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity. ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect, which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reducing oxidative stress, apoptosis and mitochondrial dysfunction. This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibition of the PI3K/AKT/mTOR expression, which could reduce mitochondrial ROS and oxidative stress-induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target to treat cardiovascular dysfunction induced by stress cardiomyopathy.

A Case of Suspected Eosinophilic Myocarditis Recognized By a Fully Noninvasive Approach and Safely Treated With Corticosteroids Despite Underlying Hepatitis C virus-related Hepatitis

Hypereosinophilic syndrome can lead to acute myocarditis with a potentially severe systolic dysfunction and serious complications. A 75-year-old patient suffering from Hepatitis C virus (HCV) related-hepatitis came to our observation for idiopatic hypereosinophilic syndrome and acute severe cardiac systolic dysfunction without coronaropathy. Cardiac magnetic resonance showed a 'patchy' subendocardial and intramyocardial late gadolinium enhancement pattern often seen in eosinophilic myocarditis (EM). Assuming EM, appropriate corticosteroid therapy was initiated and it led to clinical remission. Despite endomyocardial biopsy (EMB) is the diagnostic gold standard for EM, in this case only a noninvasive integrated imaging approach was successfully attempted. Given an adequate clinical context, in our opinion EM can be correctly recognized without EMB and so promptly and safely treated with corticosteroids, even when an underling mild HCV-hepatitis is present.

Spleen associated immune-response mediates brain-heart interaction after intracerebral hemorrhage

Background and purposeIntracerebral hemorrhage (ICH) patients frequently encounter cardiovascular complications which may contribute to increased mortality and poor long term outcome. ICH induces systemic oxidative stress and activates peripheral immune responses which are involved in the pathological cascade leading to cardiac dysfunction and heart failure after ICH. We have previously reported that ICH induces progressive cardiac dysfunction in mice without primary cardiac diseases. In this study, we have investigated the role of immune response in mediating cardiac dysfunction post ICH in mice. MethodsAdult male C57BL/6 J mice were randomly assigned to the following groups (n = 8/group): 1) sham control; 2) ICH; 3) splenectomy with ICH (ICH + Spx); 4) splenectomy alone (Spx). Echocardiography was performed at 7 and 28 days after ICH. A battery of neurological and cognitive tests were performed. Flow cytometry, western blot and immunostaining were used to test mechanisms of ICH induced cardiac dysfunction. ResultsCompared to sham control mice, Spx alone does not induce acute (7 day) or chronic (28 day) cardiac dysfunction. ICH induces significant neurological and cognitive deficits, as well as acute and chronic cardiac dysfunction compared to sham control mice. Mice subjected to ICH + Spx exhibit significantly improved neurological and cognitive function compared to ICH mice. Mice with ICH + Spx also exhibit significantly improved acute and chronic cardiac function compared to ICH mice indicated by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), decreased cardiac fibrosis, decreased cardiomyocyte hypertrophy, decreased cardiac infiltration of immune cells and decreased expression of inflammatory factor and oxidative stress in the heart. ConclusionsOur study demonstrates that splenectomy attenuates ICH-induced neurological and cognitive impairment as well as ICH-induced cardiac dysfunction in mice. Inflammatory cell infiltration into heart and immune responses mediated by the spleen may contribute to ICH-induce acute and chronic cardiac dysfunction and pathological cardiac remodeling.

Modeling Cardiac Dysfunction Following Traumatic Hemorrhage Injury: Impact on Myocardial Integrity.

Cardiac dysfunction (CD) importantly contributes to mortality in trauma patients, who survive their initial injuries following successful hemostatic resuscitation. This poor outcome has been correlated with elevated biomarkers of myocardial injury, but the pathophysiology triggering this CD remains unknown. We investigated the pathophysiology of acute CD after trauma using a mouse model of trauma hemorrhage shock (THS)-induced CD with echocardiographic guidance of fluid resuscitation, to assess the THS impact on myocardial integrity and function. Mice were subjected to trauma (soft tissue and bone fracture) and different degrees of hemorrhage severity (pressure controlled ~MABP < 35 mmHg or <65 mmHg) for 1 h, to characterize the acute impact on cardiac function. In a second study, mice were subjected to trauma and hemorrhage (MABP < 35 mmHg) for 1 h, then underwent two echocardiographic-guided resuscitations to baseline stroke volume at 60 and 120 min, and were monitored up to 180 min to study the longer impact of THS following resuscitation. Naïve and sham animals were used as controls. At 60 min post-THS injury, animals showed a lower cardiac output (CO) and stroke volume (SV) and an early rise of heart fatty acid-binding protein (H-FABP = 167 ± 38 ng/ml; 90% increase from shams, 3.54 ± 3.06 ng/ml), when subjected to severe hemorrhage and injury. Despite resuscitation, these animals maintained lower CO (6 ml/min vs. 23 ml/min), lower SV (10 μl vs. 46 μl; both ~75% decreased), and higher H-FABP (levels (340 ± 115 ng/ml vs. 10.3 ± 0.2 ng/ml; all THS vs. shams, P < 0.001) at 180 min post-THS injury. Histopathological and flow-cytometry analysis of the heart confirmed an influx of circulatory leukocytes, compared to non-injured hearts. Myocardial injury was supported by an increase of troponin I and h-FABP and the widespread ultrastructural disorganization of the morphology of sarcomeres and mitochondria. DNA fragmentation and chromatin condensation driven by leakage of apoptosis-inducing factor (AIF) may suggest a mitochondria-driven progressive cell death. THS modeling in the mouse results in cardiomyocyte damage and reduced myocardial function, which mimics the cardiac dysfunction seen in trauma patients. This CD model may, therefore, provide further understanding to the mechanisms underlying CD and act as a tool for developing cardioprotective therapeutics to improve survival after injury.