Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden: Implications for Heart Failure Risk Stratification.

BACKGROUND: Left ventricular (LV) diastolic function is primarily assessed by means of echocardiography, which has limited utility in detecting fibrosis. Cardiac magnetic resonance (CMR) readily detects and quantifies fibrosis. OBJECTIVES: In this study, the authors sought to determine the association of LV diastolic function by echocardiography with CMR-determined global fibrosis burden and the incremental value of fibrosis with diastolic function grade in prediction of total mortality and heart failure hospitalizations. METHODS: A total of 549 patients underwent comprehensive echocardiography and CMR within 30 days. Echocardiography was used to assess LV diastolic function, and CMR was used to determine LV volumes, mass, ejection fraction, replacement fibrosis, and percentage extracellular volume fraction (ECV). RESULTS: Normal diastolic function was present in 142 patients; the rest had diastolic dysfunction grades I to III, except for 18 (3.3%) with indeterminate results. The event rate was higher in patients with diastolic dysfunction compared with patients with normal diastolic function (33.4% vs 15.5; P < 0.001). The model including LV diastolic function grades II and III predicted composite outcome (C-statistic: 0.71; 95% CI: 0.67-0.76), which increased by adding global fibrosis burden (C-statistic: 0.74, 95% CI: 0.70-0.78; P = 0.02). For heart failure hospitalizations, the competing risk model with LV diastolic function grades II and III was good (C-statistic: 0.78; 95% CI: 0.74-0.83) and increased significantly with the addition of global fibrosis burden (C-statistic: 0.80; 95% CI: 0.76-0.85; P = 0.03). CONCLUSIONS: Higher grades of diastolic dysfunction are seen in patients with replacement fibrosis and increased ECV. Fibrosis burden as determined with the use of CMR provides incremental prognostic information to echocardiographic evaluation of LV diastolic function.

Tricuspid Valve Prolapse: An Uncommon Pathology Revealed by TEE.

A 73-year-old male with a history of dilated cardiomyopathy and paroxysmal atrial fibrillation underwent transthoracic echocardiography (TTE) to evaluate for endocarditis due to fever and gram-positive cocci in chains on blood cultures. TTE revealed a 3 × 8 mm mass on the ventricular aspect of the tricuspid valve ( Figure 1A ). Subsequent transesophageal echocardiography (TEE) showed that the mass in question was actually myxomatous degeneration of the tricuspid valve (TV) and redundant chordae with significant valve prolapse. Figure 1B shows the prolapsing TV leaflets at the same level as the mitral valve. Figure 1C and 1D show the valve at the level of the annulus in early systole and then prolapsing 8 mm in mid-late systole, respectively. Tricuspid valve prolapse (TVP) is uncommon, and one study of 118,000 patients reported an incidence of 0.3%.1 Since diagnostic parameters are not clearly defined, diagnosis is often determined subjectively. One objective criteria, > 2 mm atrial displacement of the TV leaflets in the TEE parasternal short-axis view, is noted to have high diagnostic accuracy. TVP is commonly associated with mitral valve prolapse. Patients with TVP have more severe tricuspid regurgitation and right-sided chamber enlargement compared to patients with no TVP. Due to the lack of significant tricuspid regurgitation in this case, the patient was reassured, and no further intervention was recommended.

Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19.

BACKGROUND: Little is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes. METHODS: We conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020). RESULTS: 126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge. CONCLUSION: Persistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.

Role of Physical Activity and Cardiac Rehabilitation in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a standard treatment for several malignancies, and >50,000 HSCT are performed annually worldwide. As survival after HSCT improves, cardiovascular disease and associated risk factors have gained importance as a significant cause of morbidity and mortality in this cohort. In this article, we detail the risk factors for cardiovascular disease and their impact in patients undergoing HSCT. Additionally, we critically review the data on the impact of physical exercise in patients undergoing HSCT. Although limited by significant heterogeneity in methodologies, small sample sizes, attrition, and lack of long-term cardiovascular follow-up, most of these studies reinforce the beneficial effects of physical activity and exercise in this patient population. Cardiac rehabilitation (CR) is a structured exercise and lifestyle modification program that is typically instituted in patients who experience acute cardiovascular events. We review the data on CR in the oncologic and nononcologic populations with an aim of building a framework for use of CR in HSCT patients.

Thromboembolic Events and Role of Point of Care Ultrasound in Hospitalized Covid-19 Patients Needing Intensive Care Unit Admission.

BACKGROUND: Covid-19 associated coagulopathy (CAC) is associated with prothrombotic state and thromboembolism. However, true incidence of thromboembolic events is difficult to determine in the ICU setting. The aim of our study was to investigate the cumulative incidence of thromboembolic events in Covid-19 patients needing intensive care unit (ICU) admission and assessing the utility of point of care ultrasound (POCUS) to screen for and diagnose lower extremity deep venous thrombosis (DVT). METHODS: We conducted a prospective observational study between April 22nd and May 26th, 2020 where all adult patients with the diagnosis of Covid-19 pneumonia admitted to 8 ICUs of Montefiore Medical Center were included. POCUS exam was performed on all patients at day 1 of ICU admission and at day 7 and 14 after the first exam. RESULTS: The primary outcome was to study the cumulative incidence of thromboembolic events in Covid-19 patients needing ICU admission. A total of 107 patients were included. All patients got POCUS exam on day 1 in the ICU, 62% got day 7 and 41% got day 14 exam. POCUS diagnosed 17 lower extremity DVTs on day 1, 3 new on day 7 and 1 new on day 14. Forty patients developed 52 thromboembolic events, with the rate of 37.3%. We found a high 45-day cumulative incidence of thromboembolic events of 37% and a high 45-day cumulative incidence of lower and upper extremity DVT of 21% and 10% respectively. Twelve (30%) patients had failure of therapeutic anticoagulation. Occurrence of a thromboembolic event was not associated with a higher risk of mortality (HR 1.08, p value = .81). CONCLUSIONS: Covid-19 patients in ICU have a high cumulative incidence of thromboembolic events, but not associated with higher mortality. POCUS is an excellent tool to help screen and diagnose DVT during a pandemic.

A Study of Policies and Guidelines for Collecting, Processing, and Storing Coronavirus Disease 2019 Patient Biospecimens for Biobanking and Research.

Biobanking has been playing a crucial role in the development of new vaccines, drugs, biotechnology, and therapeutics for the prevention and treatment of a wide range of human diseases. This puts biobanks at the forefront of responding to the ongoing worldwide outbreak of the severe pandemic, coronavirus disease 2019 (COVID-19). The leading public health institutions around the world have developed and established interim policies and guidelines for researchers and biobank staff to handle the infectious biospecimens safely and adequately from COVID-19 patients. A study of these important and complementary policies and guidelines is conducted in this study. It should be emphasized that the COVID-19 biospecimens must be collected, processed, and preserved by trained personnel equipped with right personal protective equipment to prevent the transmission of the coronavirus and ensure the specimen quality for testing and research. Six of the leading global public health organizations or institutions included in this study are the World Health Organization, the Pan American Health Organization, the U.S. Centers for Disease Control and Prevention, the Public Health England, the U.S. Food and Drug Administration, and the Office of Research at the University of California, San Francisco. In conclusion, following the recommended guidance and policies with extreme precautions is essential to ensure the quality of the collected COVID-19 biospecimens and accuracy of the conducted research or treatment, and prevent any possible transmission. Efforts from cryobiologist and biobanking engineers to optimize the protocol of COVID-19 biospecimen cryopreservation and develop the user-friendly and cost-effective devices are urgently required to meet the urgent and increased needs in the specimen biobanking and transportation.

Revascularization Strategies in Patients with Chronic Kidney Disease and Acute Coronary Syndromes.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is a highly prevalent condition that increases the incidence and complexity of acute coronary syndrome (ACS). The purpose of this review is to summarize current evidence, uncertainties, and opportunities in the management of patients with CKD and ACS, with a focus on revascularization. RECENT FINDINGS: Patients with CKD have been systematically under-represented or excluded from clinical trials in ACS. Available data, however, demonstrates that although patients with CKD and ACS benefit from revascularization, they are also less likely to receive recommended medical and revascularization therapies when compared to patients with normal kidney function. Despite the increased short-term risk of major morbidity and mortality, patients with CKD and ACS should be considered for an early invasive strategy while also trying to mitigate the risks of procedural related complications. Until evidence emerges from randomized clinical trials, the decision about revascularization strategy should involve multi-disciplinary collaboration, heart team consensus, and patient shared decision-making.

Impact of antibiotic prophylaxis on catheter-associated urinary tract infections during atrial fibrillation ablation.

PURPOSE: Urinary catheter placement is common during atrial fibrillation (AF) ablation when performed under general anesthesia. Whether patients undergoing AF ablation would benefit from prophylactic antibiotics is unknown. METHODS: Patients undergoing AF ablation in a single center from December 2011 until June 2016 were included. All patients received urinary catheters and general anesthesia. After June 2014, patients received antibiotic prophylaxis with a single dose of oral nitrofurantoin and a catheter insertion checklist performed prior to urinary catheter placement. The intervention group (group B) was compared to the pre-intervention group (group A) for development of the primary outcome. A multivariable logistic regression was performed to determine if any of the covariates were associated with catheter-associated urinary tract infection (CAUTI) development. RESULTS: There were 452 patients who underwent AF ablation during the analysis period (212 in group A and 240 in group B). The average patient age was 60 years (range 23-85) and 70% of the patients were male. Utilizing an intention to treat approach, there was a significantly lower incidence of CAUTI in the intervention group compared to controls (4.7 vs. 0.83%; OR 0.18, p = 0.029). There were no significant differences between the groups with respect to urinary tract infection risk factors or catheter duration. CONCLUSION: An intervention consisting of a single dose of nitrofurantoin in addition to performance of a catheter insertion checklist prior to urinary catheter insertion decreased CAUTI by 80% in patients undergoing AF ablation. Such interventions may be beneficial to reduce CAUTI in this group of patients.

Role of NADPH oxidase versus neutrophil proteases in antimicrobial host defense.

NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in regulating inflammation. Patients with chronic granulomatous disease, an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates (ROIs), suffer from life-threatening bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase activation is linked to the release of sequestered proteases that are posited to be critical effectors of host defense. To definitively determine the contribution of NADPH oxidase versus neutrophil serine proteases, we evaluated susceptibility to fungal and bacterial infection in mice with engineered disruptions of these pathways. NADPH oxidase-deficient mice (p47(phox-/-)) were highly susceptible to pulmonary infection with Aspergillus fumigatus. In contrast, double knockout neutrophil elastase (NE)(-/-)×cathepsin G (CG)(-/-) mice and lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are defective in neutrophil serine protease activation demonstrated no impairment in antifungal host defense. In separate studies of systemic Burkholderia cepacia infection, uniform fatality occurred in p47(phox-/-) mice, whereas NE(-/-)×CG(-/-) mice cleared infection. Together, these results show a critical role for NADPH oxidase in antimicrobial host defense against A. fumigatus and B. cepacia, whereas the proteases we evaluated were dispensable. Our results indicate that NADPH oxidase dependent pathways separate from neutrophil serine protease activation are required for host defense against specific pathogens.

Role of NADPH oxidase in host defense against aspergillosis.

NADPH oxidase plays a critical role in antimicrobial host defense, as evident in chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase characterized by severe bacterial and fungal diseases. Invasive aspergillosis and other moulds are the major cause of mortality in CGD. We also learn from CGD patients that NADPH oxidase plays an important role in regulating inflammation; CGD patients are prone to developing inflammatory diseases such as inflammatory bowel disease, obstructive granulomata of the genitourinary tract, and hypersensitivity pneumonitis. Indeed, the NADPH oxidase plays an essential role in calibrating innate and T-cell responses to control the growth of inhaled fungi while protecting against excessive and injurious inflammation. Knowledge gained on the mechanisms by which NADPH oxidase kills fungi and regulates inflammation may lead to new therapeutics for CGD and will have broad relevance to understanding host-pathogen interactions between mammals and ubiquitous moulds to which we are continually exposed.