Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Acute kidney injury in patients with acute decompensated heart failure-cardiogenic shock: Prevalence, risk factors and outcome.

BACKGROUND: Acute Kidney Injury (AKI) represents a major complication of acute heart failure and cardiogenic shock (CS). There is a paucity of data on AKI complicating acutely decompensated heart failure patients presenting with CS (ADHF-CS). We aimed to investigate AKI prevalence, risk factors and outcomes in this subgroup of patients. METHODS: Retrospective observational study on patients admitted for ADHF-CS to our 12-bed Intensive Care Unit (ICU), between January 2010 and December 2019. Demographic, clinical, and biochemical variables were collected at baseline and during hospital stay. RESULTS: Eighty-eight patients were consecutively recruited. The predominant etiologies were idiopathic dilated cardiomyopathy (47%), followed by post-ischemic (24%). AKI was diagnosed in 70 (79.5%) of patients. Forty-three out of 70 patients met the criteria for AKI at ICU admission. On multivariate analysis, a central venous pressure (CVP) higher than 10 mmHg (OR 3.9; 95%CI 1.2-12.6; p = 0.025) and serum lactate higher than 3 mmol/L (OR 4.1; 95%CI 1.01-16.3; p = 0.048) were identified to be independently associated with AKI. Age and AKI stage were independent predictors of 90-day mortality. CONCLUSION: AKI is a common and early complication of ADHF-CS. Venous congestion and severe hypoperfusion are risk factors for AKI development. Early detection and prevention of AKI could lead to better outcome in this clinical subgroup.

Tracheostomy in Mechanically Ventilated Patients With SARS-CoV-2-ARDS: Focus on Tracheomalacia.

BACKGROUND: The SARS-CoV-2 pandemic increased the number of patients needing invasive mechanical ventilation, either through an endotracheal tube or through a tracheostomy. Tracheomalacia is a rare but potentially severe complication of mechanical ventilation, which can significantly complicate the weaning process. The aim of this study was to describe the strategies of airway management in mechanically ventilated patients with respiratory failure due to SARS-CoV-2, the incidence of severe tracheomalacia, and investigate the factors associated with its occurrence. METHODS: This retrospective, single-center study was performed in an Italian teaching hospital. All adult subjects admitted to the ICU between February 24, 2020, and June 30, 2020, treated with invasive mechanical ventilation for respiratory failure caused by SARS-CoV-2 were included. Clinical data were collected on the day of ICU admission, whereas information regarding airway management was collected daily. RESULTS: A total of 151 subjects were included in the study. On admission, ARDS severity was mild in 21%, moderate in 62%, and severe in 17% of the cases, with an overall mortality of 40%. A tracheostomy was performed in 73 (48%), open surgical technique in 54 (74%), and percutaneous Ciaglia technique in 19 (26%). Subjects who had a tracheostomy performed had, compared to the other subjects, a longer duration of mechanical ventilation and longer ICU and hospital stay. Tracheomalacia was diagnosed in 8 (5%). The factors associated with tracheomalacia were female sex, obesity, and tracheostomy. CONCLUSIONS: In our population, approximately 50% of subjects with ARDS due to SARS-CoV-2 were tracheostomized. Tracheostomized subjects had a longer ICU and hospital stay. In our population, 5% were diagnosed with tracheomalacia. This percentage is 10 times higher than what is reported in available literature, and the underlying mechanisms are not fully understood.

Emergency cardiac imaging for coronavirus disease 2019 (COVID-19) in practice: a case of takotsubo stress cardiomyopathy.

BACKGROUND: Cardiovascular complications of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2) are known to be associated with poor outcome. A small number of case series and reports have described cases of myocarditis and ischaemic events, however, knowledge on the aetiology of acute cardiac failure in SARS-CoV2 remains limited. We describe the occurrence and risk stratification imaging correlates of 'takotsubo' stress cardiomyopathy presenting in a patient with Coronavirus Disease 2019 (COVID-19) in the intensive care unit. An intubated 53-year old patient with COVID19 suffered acute haemodynamic collapse in the intensive care unit, and was thus investigated with transthoracic echocardiography (TTE), 12-lead electrocardiograms (ECG) and serial troponins and blood tests, and eventually coronary angiography due to clinical suspicion of ischaemic aetiology. Echocardiography revealed a reduced ejection fraction, with evident extensive apical akinesia spanning multiple coronary territories. Troponins and NT-proBNP were elevated, and ECG revealed ST elevation: coronary angiography was thus performed. This revealed no significant coronary stenosis. Repeat echocardiography performed within the following week revealed a substantial recovery of ejection fraction and wall motion abnormalities. Despite requirement of a prolonged ICU stay, the patient now remains clinically stable, and is on spontaneous breathing. CONCLUSION: This case report presents a case of takotsubo stress cardiomyopathy occurring in a critically unwell patient with COVID19 in the intensive care setting. Stress cardiomyopathy may be an acute cardiovascular complication of COVID-19 infection. In the COVID19 critical care setting, urgent bedside echocardiography is an important tool for initial clinical assessment of patients suffering haemodynamic compromise.

Predicting survival in patients with acute decompensated heart failure complicated by cardiogenic shock.

BACKGROUND: Acute decompensated heart failure (ADHF) complicated by cardiogenic shock (CS) has unique pathophysiological background requiring specific patient stratification, management and therapeutic targets. Accordingly, the aim of this study was to derive a simple stratification tool to predict survival in patients with ADHF complicated by CS. METHODS AND RESULTS: Using logistic regression, univariable testing was performed to identify the variables potentially associated with 28-day mortality. We propose a new logistic model (ALC-Shock score) based on three easy parameters (age, serum creatinine and serum lactate at the ICU admission) as a powerful predictor of survival or successful bridge to heart replacement therapy at 28-day follow-up in this specific population. A multivariable analysis (logistic model) was performed to evaluate the association between selected variables and outcome (overall death at 28-day follow up). The score was then validated in a different cohort of 93 ADHF-CS patients and compared to a previous developed score (the Cardshock score).Overall, 28-day mortality was 34%. The ALC-shock score showed better discrimination (Area Under the Curve-AUC- 0.82; 95% CI 0.73-0.91) as compared to the Cardshock score (AUC 0.67; 95% CI 0.55-0.79) (p = 0.009) to predict 28-days overall mortality. In the validation cohort the AUC for the ALC-shock score was 0.66. CONCLUSIONS: A simple score including age, lactates and creatinine on admission could be considered to predict short-term mortality in CS-ADHF patients in order to drive towards a treatment intensification.

The repurposed use of anesthesia machines to ventilate critically ill patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: The surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice. METHODS: We designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group. RESULTS: Complete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75-9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns. CONCLUSIONS: Our results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic. CLINICAL TRIAL NUMBER: Not applicable.

The repurposed use of anesthesia machines to ventilate critically ill patients with Coronavirus Disease 2019 (COVID-19).

BackgroundThe surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice.MethodsWe designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group.ResultsComplete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75-9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns.ConclusionsOur results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic.Clinical Trial NumberNot applicable.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

Update on acute myocarditis.

Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.

Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.

BACKGROUND: Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap. METHODS AND DESIGN: The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients. IMPLICATIONS: The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.

Takotsubo syndrome as a complication in a critically ill COVID-19 patient.

Coronavirus disease 2019 (COVID-19) patients with cardiac injury have an increased risk of mortality. It remains to be determined the mechanism of cardiac injury and the identification of specific conditions that affect the heart during COVID-19. We present the case of a 76-year-old woman with COVID-19 pneumonia that developed a takotsubo syndrome (TTS). Although the patient presented normal left ventricular ejection fraction and normal levels of troponin on admission, after 16 days in intensive care unit due to respiratory distress, she suddenly developed cardiogenic shock. Shock occurred few hours after a spontaneous breathing trial through her tracheostomy. Bed-side echocardiographic revealed apical ballooning promptly supporting the diagnosis of TTS. She was successfully treated with deep sedation and low dosage of epinephrine. The relevance of this case is that TTS can occur in the late phase of COVID-19. Awareness of late TTS and bed-side echocardiographic evaluation can lead to prompt identification and treatment.

Safety and efficacy of anti-il6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: A comparative analysis.

BACKGROUND: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19. METHODS: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used. RESULTS: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events. DISCUSSION: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events. FINANCIAL SUPPORT: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper.