ABSTRACT
Left ventricular free wall rupture is a lethal complication of myocardial infarction. Although emergent surgical repair is the treatment of choice, the method of repair remains highly individualized. This report presents a case of spontaneous coronary artery dissection in a patient with Turner syndrome that led to left ventricular free wall rupture and was successfully repaired on cardiopulmonary bypass using a suture-free technique with the EVARREST Fibrin Sealant Patch.
Subject(s)
Heart Rupture, Post-Infarction , Heart Rupture , Myocardial Infarction , Humans , Treatment Outcome , Myocardial Infarction/complications , Fibrinogen , Heart Rupture/complications , Heart Rupture/surgeryABSTRACT
BACKGROUND: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and after lower respiratory tract PCR testing, Legionella was determined to be the cause. She was successfully treated and decannulated from VV-ECMO after eight days. CASE PRESENTATION: A 53-year-old female presented with one week of dyspnea and a positive COVID-19 test. She was hypoxemic, hypotensive and had bilateral infiltrates on imaging. She received supplemental oxygen, intravenous fluids, vasopressors, broad spectrum antibiotics, and was transferred to a tertiary care center. She developed progressive hypoxemia and suffered a cardiac arrest, requiring ten minutes of CPR and endotracheal intubation to achieve return of spontaneous circulation. Despite mechanical ventilation and paralysis, she developed refractory hypoxemia and was cannulated for VV-ECMO. Dexamethasone and remdesivir were given for presumed COVID-19. Bronchoscopy with bronchoalveolar lavage (BAL) performed with PCR testing was positive for Legionella pneumophila and negative for COVID-19. Steroids and remdesivir were discontinued and she was treated with azithromycin. Her lung compliance improved, and she was decannulated after eight days on VV-ECMO. She was discharged home on hospital day 16 breathing room air and neurologically intact. CONCLUSIONS: This case illustrates the utility of rapid PCR testing to diagnose Legionella in patients with respiratory failure and the early use of VV-ECMO in patients with refractory hypoxemia secondary to Legionella infection. Moreover, many patients encountered in the ICU may have prior COVID-19 immunity, and though a positive COVID-19 test may be present, further investigation with lower respiratory tract PCR testing may provide alternative diagnoses. Patients with ARDS should undergo Legionella-specific testing, and if Legionella is determined to be the causative organism, early VV-ECMO should be considered in patients with refractory hypoxemia given reported high survival rates.
Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Heart Arrest , Legionella , Respiratory Distress Syndrome , Humans , Female , Middle Aged , Extracorporeal Membrane Oxygenation/methods , COVID-19/complications , COVID-19/therapy , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Hypoxia/complications , Heart Arrest/etiology , Heart Arrest/therapyABSTRACT
BACKGROUND: The incidence of infective endocarditis (IE) is rapidly increasing. Contemporary outcomes following high-risk double valve surgery (DVS) for IE are not well described. METHODS: Between 2001 and 2021, 211 patients with IE underwent combined aortic and mitral valve surgery at a tertiary care referral center. Data from the Society of Thoracic Surgeons registry, including demographics, operative details, and outcomes, were collected. Risk factors for 30-day and 1-year-mortality were analyzed. Survival was analyzed using Kaplan-Meier and Cox proportional hazards modeling. RESULTS: The study cohort had a male preponderance (73%), with a median age of 56 years (interquartile range [IQR], 44 to 63 years). Forty-five patients (21%) had a history of intravenous (IV) drug abuse, 50 (24%) were on preoperative dialysis, and 50 (24%) had prosthetic valve endocarditis. Thirty-day and 1-year mortality were 14% (n = 30) and 30% (n = 61), respectively. On multivariable Cox regression adjusting for age, prosthetic valve endocarditis, postoperative intra-aortic balloon pump (IABP), history of dialysis (adjusted hazard ratio [aHR], 1.9; 95% confidence interval [CI], 1.3 to 2.9; P = .002) and IV drug abuse (aHR, 2.0; 95% CI, 1.1-3.5; P = .02) were predictive of decreased survival. Undergoing surgery after 2010 was predictive of improved survival (aHR, 0.5; 95% CI, 0.3 to 0.8; P = .006). These patients were more likely to undergo urgent/emergent surgery (83% vs 29%; P < .001) and less likely to have an aortic root abscess (40% vs 58%; P = .03) or to require the commando procedure (13% vs 33%; P = .002). CONCLUSIONS: In this large series evaluating outcomes of DVS for IE in the modern era, although the mortality risk remained elevated, improving outcomes may be associated with earlier surgical intervention before significant disease progression. Multidisciplinary evaluation for complex IE may be considered to better understand the optimal timing and repair strategy.
ABSTRACT
Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts. Within these cell types, inflammatory signatures were negative predictors of recovery, and downregulation of RUNX1 was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. Cardiac recovery mediated by BET inhibition in mice led to decreased macrophage and fibroblast Runx1 expression and diminished chromatin accessibility within a Runx1 intronic peak and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
ABSTRACT
BACKGROUND: The optimal repair strategy for tetralogy of Fallot remains controversial. This report presents a 14-year evolution of management of the pulmonary valve (PV) from transannular patch to valve-sparing repair to neovalve creation using living right atrial appendage tissue. METHODS: A retrospective review of 172 consecutive patients undergoing complete repair for TOF between January 2007 and June 2021 was performed. Clinical and follow-up data were analyzed by repair group. Neopulmonary valve (NPV) creation using right atrial appendage tissue was introduced in 2019. Failure of valve-sparing repair was defined as needing reintervention for recurrent right ventricular outflow tract obstruction (RVOTO). RESULTS: Median age and weight at repair were 4.9 months and 6 kg, respectively. Median preoperative PV size and z-score were 6.4 mm (5.2-8.3 mm) and -3.2 (-4.1 to -2.1), respectively. Patients who underwent valve-sparing repair had larger PV size and z-score compared with patients who underwent transannular patch procedures (8 mm vs 5.6 mm; -2.1 vs -3.2; both P < .001). There were no hospital mortalities. Overall follow-up was 44 months. At last follow-up, 10% of patients who underwent valve-sparing repair had repeat intervention for recurrent RVOTO. Patients who had failed valve-sparing repair had significantly lower PV z-scores (-2.6 vs -1.9; P = .01). An NPV was used in 8 patients with a median PV z-score of -4 (-4.7 to -3.9). At 6 months, 6 patients (75%) had mild or trivial pulmonary insufficiency after NPV placement. CONCLUSIONS: Repair of tetralogy of Fallot is a safe operation with excellent outcomes. Valve-sparing repair avoids right ventricular dilation but may fail for RVOTO at a PV z-score <-2. NPV creation offers an alternative option in patients with a small PV.
Subject(s)
Cardiac Surgical Procedures , Pulmonary Valve Insufficiency , Pulmonary Valve , Tetralogy of Fallot , Ventricular Outflow Obstruction, Right , Humans , Infant , Pulmonary Valve/surgery , Tetralogy of Fallot/surgery , Cardiac Surgical Procedures/methods , Pulmonary Valve Insufficiency/etiology , Pulmonary Valve Insufficiency/surgery , Reoperation , Retrospective Studies , Treatment OutcomeSubject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve Annuloplasty , Mitral Valve Insufficiency , Humans , Mitral Valve Annuloplasty/adverse effects , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Treatment Outcome , Prosthesis DesignSubject(s)
Cardiac Surgical Procedures , Heart Valve Prosthesis Implantation , Tricuspid Valve Insufficiency , Humans , Tricuspid Valve/diagnostic imaging , Tricuspid Valve/surgery , Cardiac Surgical Procedures/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Humans , Proteome , Ligands , Drug DesignABSTRACT
INTRODUCTION: Slipping rib syndrome (SRS) or subluxation of the medial aspect of the lower rib costal cartilages is an underdiagnosed cause of debilitating pain in otherwise healthy children. Costal cartilage excision may provide definitive symptom relief. However, limited data exist on the natural history, difficulty in diagnosis, and patient-reported outcomes for SRS in children. METHODS: We performed a single-institution descriptive study using chart review and a patient-focused survey for patients who underwent surgery for SRS from 2012 to 2020. Data regarding demographics, symptoms, diagnostic workup, and patient-reported outcomes were collected. RESULTS: Surgical resection was performed in 13 children. The median age at symptom onset was 12.5 y [IQR 9.7, 13.9], with a preponderance of girls (10, 77%). Eight patients participated in competitive athletics at the time of symptom onset. Prior to diagnosis, patients were seen by a median 3 [IQR 2, 5] providers with a median of 4 [IQR 3, 6] non-diagnostic imaging exams performed. The children included in the study underwent surgery for left (8), bilateral (4), and right (1) SRS. Two were lost to follow-up. At median post-op follow-up of 3.5 mo [IQR 1.2, 9.6], 73% (8/11) had returned to full activity. One reported non-limiting persistent pain symptoms. CONCLUSIONS: Lack of knowledge regarding SRS may result in delayed diagnosis, excessive testing, and limitation of physical activity. Operative treatment appears to provide durable relief and should be considered for children with SRS. The challenge remains to decrease the number of non-diagnostic exams and time to diagnosis.
Subject(s)
Costal Cartilage , Orthopedic Procedures , Humans , Child , Female , Syndrome , Ribs/surgery , Orthopedic Procedures/adverse effects , Orthopedic Procedures/methods , PainABSTRACT
Long-standing effects of pulmonary regurgitation after transannular patch repair in Tetralogy of Fallot (ToF) can be especially deleterious in the setting of combined ToF and complete atrioventricular septal defect (CAVSD). We present a technique for a complete repair of combined ToF/CAVSD using right atrial appendage tissue to create a competent neo-pulmonary valve. This technique provides advantages of right heart protection via pulmonary valve competence and the use of living tissue capable of growth with the patient, potentially obviating the need for repeat interventions.
Subject(s)
Cardiac Surgical Procedures , Pulmonary Valve , Tetralogy of Fallot , Cardiac Surgical Procedures/methods , Heart Septal Defects , Humans , Infant , Pulmonary Valve/surgery , Retrospective Studies , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/surgery , Treatment OutcomeABSTRACT
Glutathione has long been suspected to be the primary low molecular weight compound present in all cells promoting the oxidative protein folding, but twenty years ago it was found "not guilty". Now, new surprising evidence repeats its request to be the "smoking gun" which reopens the criminal trial revealing the crucial involvement of this tripeptide.
Subject(s)
Glutathione/metabolism , Oxygen/metabolism , Protein Folding , Animals , Cysteine/metabolism , Humans , Protein Processing, Post-TranslationalABSTRACT
The coronavirus disease-2019 (COVID-19) pandemic has rapidly spread across the world. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first appeared in Wuhan, China in December, 2019. Ever increasing data is continuing to emerge about the impact of COVID-19 on cardiovascular tissue and other organ system. Clinical features associated with COVID-19 suggest that endothelial cell dysfunction and microvascular thrombosis are to a large extent contributing to resultant multi-organ complications. This review is aimed at highlighting the critical aspects associated with COVID-19 and its presumed microvascular angiopathic consequences on the cardiovascular system leading to multi-organ dysfunction.
ABSTRACT
Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up to now, coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains has remained elusive. Here, we investigate the eye-lens protein γB-crystallin in the ribosomal exit tunnel. Using mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance and cryo-electron microscopy, we show that thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding.