Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, ...myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Left Ventricular Assist Devices for Lifelong Support Pinney, Sean P., MD; Anyanwu, Anelechi C., MD; Lala, Anuradha, MD ...
Journal of the American College of Cardiology,
06/2017, Letnik:
69, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Abstract Continuous-flow left ventricular assist devices (LVADs) have revolutionized advanced heart failure care. These compact, fully implantable heart pumps are capable of providing meaningful ...increases in survival, functional capacity, and quality of life. Implantation volumes continue to grow, but several challenges remain to be overcome before LVADs will be considered as the therapy of choice for all patients with advanced heart failure. They must be able to consistently extend survival for the long term (7 to 10 years), rather than the midterm (3 to 5 years) more typical of contemporary devices; they must incorporate design elements that reduce shear stress and avoid stasis to reduce the frequent adverse events of bleeding, stroke, and pump thrombosis; and they must become more cost-effective. The advancements in engineering, implantation technique, and medical management detailed in this review will highlight the progress made toward achieving lifelong LVAD support and the challenges that remain.
Omega-3 polyunsaturated fatty acid (ω-3 PUFA) therapy continues to show great promise in primary and, particularly in secondary prevention of cardiovascular (CV) diseases. The most compelling ...evidence for CV benefits of ω-3 PUFA comes from 4 controlled trials of nearly 40,000 participants randomized to receive eicosapentaenoic acid (EPA) with or without docosahexaenoic acid (DHA) in studies of patients in primary prevention, after myocardial infarction, and most recently, with heart failure (HF). We discuss the evidence from retrospective epidemiologic studies and from large randomized controlled trials showing the benefits of ω-3 PUFA, specifically EPA and DHA, in primary and secondary CV prevention and provide insight into potential mechanisms of these observed benefits. The target EPA + DHA consumption should be at least 500 mg/day for individuals without underlying overt CV disease and at least 800 to 1,000 mg/day for individuals with known coronary heart disease and HF. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA ω-3 PUFA that provides maximal cardioprotection in those at risk of CV disease as well in the treatment of atherosclerotic, arrhythmic, and primary myocardial disorders.
The efficacy, safety, and clinical importance of extended-duration thromboprophylaxis (EDT) for prevention of venous thromboembolism (VTE) in medical patients remain unclear. We compared the efficacy ...and safety of EDT in patients hospitalized for medical illness.
Electronic databases of PubMed/MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were searched from inception to March 21, 2019. We included randomized clinical trials (RCTs) reporting use of EDT for prevention of VTE. We performed trial sequential and cumulative meta-analyses to evaluate EDT effects on the primary efficacy endpoint of symptomatic VTE or VTE-related death, International Society on Thrombosis and Haemostasis (ISTH) major or fatal bleeding, and all-cause mortality. The pooled number needed to treat (NNT) to prevent one symptomatic or fatal VTE event and the number needed to harm (NNH) to cause one major or fatal bleeding event were calculated. Across 5 RCTs with 40,247 patients (mean age: 67-77 years, proportion of women: 48%-54%, most common reason for admission: heart failure), the duration of EDT ranged from 24-47 days. EDT reduced symptomatic VTE or VTE-related death compared with standard of care (0.8% versus 1.2%; risk ratio RR: 0.61, 95% confidence interval CI: 0.44-0.83; p = 0.002). EDT increased risk of ISTH major or fatal bleeding (0.6% versus 0.3%; RR: 2.04, 95% CI: 1.42-2.91; p < 0.001) in both meta-analyses and trial sequential analyses. Pooled NNT to prevent one symptomatic VTE or VTE-related death was 250 (95% CI: 167-500), whereas NNH to cause one major or fatal bleeding event was 333 (95% CI: 200-1,000). Limitations of the study include variation in enrollment criteria, individual therapies, duration of EDT, and VTE detection protocols across included trials.
In this systematic review and meta-analysis of 5 randomized trials, we observed that use of a post-hospital discharge EDT strategy for a 4-to-6-week period reduced symptomatic or fatal VTE events at the expense of increased risk of major or fatal bleeding. Further investigations are still required to define the risks and benefits in discrete medically ill cohorts, evaluate cost-effectiveness, and develop pathways for targeted implementation of this postdischarge EDT strategy.
PROSPERO CRD42018109151.
Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the ...possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.
We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.
A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.
In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).
The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc., formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into clinical trials for durable circulatory ...support in patients with medically refractory advanced-stage heart failure. This centrifugal, fully magnetically levitated, continuous-flow pump is engineered with the intent to enhance hemocompatibility and reduce shear stress on blood elements, while also possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and destination therapy (DT) are established dichotomous indications for durable left ventricular assist device (LVAD) support, clinical practice has challenged the appropriateness of these designations. The introduction of novel LVAD technology allows for the development of clinical trial designs to keep pace with current practices. The prospective, randomized Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also St. Jude Medical, Inc.). The innovative trial design includes patients enrolled under a single inclusion and exclusion criteria , regardless of the intended use of the device, with outcomes ascertained in the short term (ST, at 6 months) and long term (LT, at 2 years). This adaptive trial design includes a pre-specified safety phase (n = 30) analysis. The ST cohort includes the first 294 patients and the LT cohort includes the first 366 patients for evaluation of the composite primary end-point of survival to transplant, recovery or LVAD support free of debilitating stroke (modified Rankin score >3), or re-operation to replace the pump. As part of the adaptive design, an analysis by an independent statistician will determine whether sample size adjustment is required at pre-specified times during the study. A further 662 patients will be enrolled to reach a total of 1,028 patients for evaluation of the secondary end-point of pump replacement at 2 years.
•Expanded Access (EA) is the use of an investigational drug outside of a clinical investigation.•Emergency Use Authorizations (EUAs) are issued during public health emergencies.•The pandemic has ...forced us to recognize weaknesses associated with our current EA and EUA system.
The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, uncertainties around new vaccine safety and effectiveness have spawned interest in other pharmacological options. Experimental drugs can also be approved under the FDA Emergency Use Authorization (EUA) program, designed to combat infectious disease and other threats. Here, we review the US experience in 2020 with pharmacological EA and EUA approvals during the pandemic. We also provide a description of, and clinical rationale for, each of the EA- or EUA-approved drugs (e.g. remdesivir, convalescent plasma, propofol 2%, hydroxychloroquine, ruxolitinib, bamlanivimab, baricitinib, casirivimab plus imdevimab) during the pandemic and concluding reflections on the EA program and its potential future uses.
Several drugs have been authorized by the US FDA through the Expanded Access and/or the Emergency Use Authorization programs during the COVID-19 pandemic. How well did these programs function and what have we learned?
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