Mechanical and interventional support for heart failure with preserved ejection fraction: A review.

INTRODUCTION: Restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) are two disease processes that are known to progress to heart failure with preserved ejection fraction (HFpEF). Pharmacologic therapies for HFpEF have not improved patient outcomes or reduced mortality in this patient cohort; thus, there continues to be substantial interest in other treatment strategies, including surgical interventions and devices. In this article, we explore and report the current utility of percutaneous therapies and surgically implanted mechanical support in the treatment of patients with HFpEF. RESULTS: Treatment strategies include percutaneous interventions with interatrial shunts, left atrial assist devices (LAADs), and ventricular assist devices (VADs) in various configurations. Although VADs have been employed to treat patients with heart failure with reduced ejection fraction, their efficacy is limited in those with RCM and HCM. A left atrial-to-aortic VAD has been proposed to directly unload the left atrium, but data is limited. Alternatively, a LAAD could be placed in the mitral position and simultaneously unload the left atrium, while filling the left ventricle. CONCLUSION: A left atrial assist device in the mitral position is a promising solution to address the hemodynamic abnormalities in RCM and HCM; these pumps, however, are still under development.

Outcomes of extracorporeal membrane oxygenation in acute respiratory distress syndrome due to COVID-19: The lessons learned from the first wave of COVID-19.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) has been used as a refractory treatment for acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19), but there has been little evidence of its efficacy. We conducted this study to share our experience using ECMO as a bridge to recovery for ARDS due to COVID-19. METHODS: All adult patients who were placed on ECMO for ARDS due to COVID-19 between April 2020 and June 2020 (during the first wave of COVID-19) were identified. The clinical characteristics and outcomes of these patients were analyzed with a specific focus on the differences between patients who survived to hospital discharge and those who did not. RESULTS: In total, 20 COVID-19 patients were included in this study. All patients were placed on veno-veno ECMO. Comparing survivors and non-survivors, older age was found to be associated with hospital mortality (p = .02). The following complications were observed: renal failure requiring renal replacement therapy (35%, n = 7), bacteremia during ECMO (20%, n = 4), coinfection with bacterial pneumonia (15%, n = 3), cannula site bleeding (15%, n = 3), stroke (10%, n = 2), gastrointestinal bleeding (10%, n = 2), and liver failure (5%, n = 1). The complications associated with patient mortality were culture-positive septic shock (p = .01), culture-negative systemic inflammatory response syndrome (p = .01), and renal failure (p = .01). The causes of death were septic shock (44%, n = 4), culture-negative systemic inflammatory response syndrome (44%, n = 4), and stroke (11%, n = 1). CONCLUSIONS: Based on our experience, ECMO can improve refractory ARDS due to COVID-19 in select patients. Proper control of bacterial infections during COVID-19 immunomodulation therapy may be critical to improving survival.

Outcomes of extracorporeal membrane oxygenation in influenza versus COVID-19 during the first wave of COVID-19.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a refractory treatment for acute respiratory distress syndrome (ARDS) due to influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also referred to as coronavirus disease 2019 [COVID-19]). We conducted this study to compare the outcomes of influenza patients treated with veno-venous-ECMO (VV-ECMO) to COVID-19 patients treated with VV-ECMO, during the first wave of COVID-19. METHODS: Patients in our institution with ARDS due to COVID-19 or influenza who were placed on ECMO between August 1, 2010 and September 15, 2020 were included in this comparative, retrospective study. To improve homogeneity, only VV-ECMO patients were analyzed. The clinical characteristics and outcomes were extracted and analyzed. RESULTS: A total of 28 COVID-19 patients and 17 influenza patients were identified and included. ECMO survival rates were 68% (19/28) in COVID-19 patients and 94% (16/17) in influenza patients (p = .04). Thirty days survival rates after ECMO decannulation were 54% (15/28) in COVID-19 patients and 76% (13/17) in influenza patients (p = .13). COVID-19 patients spent a longer time on ECMO compared to flu patients (21 vs. 12 days; p = .025), and more COVID-19 patients (26/28 vs. 2/17) were on immunomodulatory therapy before ECMO initiation (p < .001). COVID-19 patients had higher rates of new infections during ECMO (50% vs. 18%; p = .03) and bacterial pneumonia (36% vs. 6%; p = .024). CONCLUSIONS: COVID-19 patients who were treated in our institution with VV-ECMO had statistically lower ECMO survival rates than influenza patients. It is possible that COVID-19 immunomodulation therapies may increase the risk of other superimposed infections.

Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.

RATIONALE: Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome. OBJECTIVES: To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers. METHODS: Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated. MEASUREMENTS AND MAIN RESULTS: In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota. CONCLUSIONS: We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.

Outcomes of extracorporeal membrane oxygenation in immunosuppressed vs. Immunocompetent patients.

INTRODUCTION: Immunosuppressed hosts represent a growing group of patients who suffer acute respiratory failure and may be considered for therapies such as extracorporeal membrane oxygenation (ECMO). OBJECTIVES: We conducted this retrospective study to determine whether acutely or chronically immunosuppressed patients placed on ECMO for cardiac and/or respiratory failure in our institution have different outcomes than immunocompetent patients placed on ECMO in our institution. METHODS: Adult patients placed on ECMO between June 31, 2010 and July 7, 2021 were identified within an IRB-approved database. Data was retrospectively extracted from the database and patients' medical records. Patients who survived ECMO decannulation were sub-grouped by the presence of acute or chronic immunosuppression, defined by the use of high-dose steroids or immunosuppressive agents for greater than four weeks prior to ECMO initiation. We analyzed and compared baseline characteristics and clinical outcomes using chi-squared tests for categorical variables and a one-way analysis of variance (ANOVA) for continuous variables. RESULTS: 385 patients were included in this study, with 39 identified as chronically immunosuppressed, 49 as acutely immunosuppressed, and 297 as immunocompetent. There was no statistical difference in ECMO survival (respectively 54%, 59%, 65% p = 0.359) or 30-day survival (33%, 51%, 48% p = 0.149) for chronically immunosuppressed, acutely immunosuppressed, and immunocompetent, respectively. There were significant differences in rates of pre-ECMO COVID infection (p<0.001), coronary artery disease (p<0.001), smoking (p = 0.003), and acute kidney injury (p = 0.032). Acutely immunosuppressed patients had the highest rates of new infections during ECMO (p = 0.006). CONCLUSION: When compared to immunocompetent patients, both acutely and chronically immunosuppressed patients had no significant difference in ECMO survival or 30-day survival. Acutely immunosuppressed patients had less comorbidities than chronically immunosuppressed patients, but they were more commonly infected during ECMO. ECMO may still be a valuable tool in appropriately selected patients with refractory respiratory or cardiac failure.

Systemic Inflammatory Response Syndrome After Extracorporeal Membrane Oxygenation Decannulation in COVID-19 Patients.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is frequently observed following decannulation from extracorporeal membrane oxygenation (ECMO). Differentiating cytokine release due to infection from endothelial injury from cannula removal and/or discontinuation from the ECMO circuit has been shown to impact treatment and outcomes. This response, however, may be complicated in COVID-19 patients due to prevalent glucocorticoid and immune modulator use. It remains unclear whether COVID-19 infection and/or associated immune modulator use impact the incidence of SIRS following decannulation. OBJECTIVES: The aim of this study is to investigate the incidence of the SIRS phenomenon and associated outcomes in patients with COVID-19 after ECMO decannulation. METHODS: An IRB-approved retrospective chart review of all patients who survived ECMO between June 31, 2010 and July 7, 2021 was done to identify patients who experienced SIRS within 48 hours of decannulation from ECMO support. Patients with COVID-19 were confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV2. SIRS was confirmed when two out of three of the following criteria were met: fever, leukocytosis, and/or initiation/escalation of vasopressors. Patients who developed post-ECMO SIRS were then distinguished based on the presence of infection. Infection was defined by the presence of either a new or positive culture following decannulation. We compared the incidence of SIRS and infection within 48 hours of decannulation in patients with and without COVID-19. RESULTS: We identified 227 eligible patients who survived ECMO. Twenty-eight patients (12%) had COVID-19. Of these patients, ten patients with COVID-19 (36%) experienced post-ECMO SIRS, including those with true SIRS (n=3) and associated infections (n=7). Five of the ten patients with COVID-19 who experienced post-ECMO SIRS were exposed to immune modulators within two weeks of decannulation. Ninety-five (42%) patients without COVID-19 developed post-ECMO SIRS. Thirty-day survival in COVID patients who experienced post-ECMO SIRS compared to COVID patients who did not experience post-ECMO SIRS was 73% vs. 94%. (p=0.11). CONCLUSION: Post-ECMO SIRS is common. The incidence of SIRS following decannulation was similar when historically compared to non-COVID patients who survived ECMO in a previously reported cohort from our institution. Immune-modulation exposure within two weeks of decannulation did not affect the incidence of SIRS in patients with COVID-19.

Infection following CF-LVAD exchange for non-infectious indications: A systematic review and meta-analysis.

INTRODUCTION: Patients on continuous flow left ventricular assist devices (CF-LVADs) often require CF-LVAD exchange. The purpose of this study was to investigate the incidence of infection following CF-LVAD exchange performed for non-infectious indications. METHODS: An electronic literature search was performed to identify all studies of patients undergoing CF-LVAD exchange for pump thrombosis or device malfunction. Of 2,698 articles identified, 6 studies with 81 total patients met the inclusion criteria. Cohort-level data were pooled for meta-analysis. RESULTS: Mean patient age was 60 years (95% CI: 41-78), and 74% were male (95% CI: 61-84). Pump thrombosis was the most common indication for exchange in 70% of patients (95% CI: 47-86). Other indications were driveline fracture and electrical malfunction in 21% (95% CI: 5-56) and 12% (95% CI: 4-33) of patients, respectively. Prior to exchange, 95% of patients were on HeartMate II (HM2) LVADs (95% CI: 86-98) and average duration of support for these patients was 27.1 months (95% CI: 9.3-44.8). The majority were placed on a HM2 following exchange (88% (95% CI: 45-98)) versus HM3 (12% (95% CI: 2-55)). Follow-up was an average of 16.4 months (95% CI: 6.8-26.0). Following exchange, 16 of 81 patients developed infection, with pooled mean incidence of 24% (95% CI: 14-38). 30-day mortality was 14% (95% CI: 7-26). Survival at follow-up was 65% (95% CI: 52-76). CONCLUSIONS: Infection following CF-LVAD exchange can occur at rates higher than those observed with primary implantation; therefore, effective strategies need to implemented early and consistently to help lower infections rates and help improve outcomes following exchange.