Outcomes in solid organ transplant recipients receiving organs from a donor with Fusarium solani species complex meningitis.

BACKGROUND: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico. METHODS: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS. RESULTS: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1-3)-ß-d-glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis. CONCLUSION: Antifungal prophylaxis may be useful in preventing donor-derived infections in recipients of organs from donors that are found to have Fusarium meningitis.

Evaluation of a New Aptamer-Based Array for Soluble Suppressor of Tumorgenicity (ST2) and N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP) in Heart Failure Patients.

BACKGROUND: Recent advances in multi-marker platforms offer faster data generation, but the fidelity of these methods compared to the ELISA is not established. We tested the correlation and predictive performance of SOMAscan vs. ELISA methods for NTproBNP and ST2. METHODS: Patients ≥ 18 years with heart failure and ejection fraction < 50% were enrolled. We tested the correlation between SOMA and ELISA for each biomarker and their association with outcomes. RESULTS: There was good correlation of SOMA vs. ELISA for ST2 (ρ = 0.71) and excellent correlation for NTproBNP (ρ = 0.94). The two versions of both markers were not significantly different regarding survival association. The two ST2 assays and NTproBNP assays were similarly associated with all-cause mortality and cardiovascular mortality. These associations remained statistically significant when adjusted for MAGGIC risk score (all p < 0.05). CONCLUSION: SOMAscan quantifications of ST2 and NTproBNP correlate to ELISA versions and carry similar prognosis.

Tissue plasminogen activator in left ventricular assist device-related intravascular hemolysis after failed augmented anticoagulation.

OBJECTIVES: We sought to examine the efficacy and safety of adding fibrinogen-guided low-dose multi-day Alteplase™ tissue plasminogen activator (tPA) in the management of intravascular hemolysis (IVH) in patients with the HeartMate II (HM-II) continuous flow (CF) left ventricular assist device (LVAD) who failed to achieve IVH resolution with conventional augmented anticoagulation (AAC). BACKGROUND: IVH in patients with LVAD is often treated with AAC, failing which pump exchange is considered. We hypothesized that a trial of low-dose tPA after failed AAC therapy could resolve IVH and prevent pump exchange in some patients. METHODS: We performed a retrospective study of 31 HM-II CF LVAD patients admitted to our center from January 2015 to January 2020 for IVH management who received tPA following failed AAC. Primary 6-month outcomes included successful IVH resolution, unsuccessful IVH resolution requiring pump exchange, gastrointestinal bleeding, ischemic and hemorrhagic cerebrovascular accident (CVA), and death. RESULTS: Thirty-one patients with IVH were treated with tPA following failed AAC. Successful resolution of IVH occurred in 22/31 (71%) patients. Pump exchange occurred in 9/31 (29%) patients. Gastrointestinal bleeding occurred in 7/31 (22.6%) patients. Ischemic CVA occurred in 6/31 (19.4%) patients. CONCLUSIONS: Management of IVH with administration of low-dose tPA after failed AAC is feasible and may prevent pump exchange in some patients.

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience.

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart-lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59 years (interquartile range, 48.25-73.25). All patients were classified as having mild-moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n = 5), followed by cough and chills 67% (n = 4). All admitted patients (n = 5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23 days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.

Implication of Ventricular Assist Devices in Extracorporeal Membranous Oxygenation Patients Listed for Heart Transplantation.

The new allocation criteria classify patients on veno-arterial extracorporeal membranous oxygenation (VA-ECMO) as the highest priority for receiving orthotopic heart transplantation (OHT) especially if they are considered not candidates for ventricular assist devices. The outcomes of patients who receive ventricular assist devices (VADs) after being listed for heart transplantation with VA-ECMO is unknown. We analyzed 355 patients listed for OHT with VA-ECMO from the United Network for Organ Sharing database from 2006 to 2014. Univariate and multivariate Cox proportional-hazards models were used to determine the contribution of prognostic variables to the outcome. Thirty-three patients (9.3%) received VADs (15 dischargeable, 7 non-dischargeable VADs). The VAD and non-VAD groups had similar listing characteristics except that the VAD group were more likely to have non-ischemic cardiomyopathy (48.5% vs. 25.2%), and less likely to be obese (6.1% vs. 25.2%) or have a history of prior organ transplant (3% vs. 31.1%). Patients who underwent VAD implantation had more days on the list (median 189 vs. 14 days) compared to the non-VAD group. Amongst the patients who had VADs, (25/33) 75.5% patients were subsequently transplanted with similar post-transplant survival compared to the non-VAD group (72% vs. 60.5%; p = 0.276). Predictors of one-year post-transplant mortality included panel reactive antibodies (PRA) class I ≥ 20%, recipient smoking history, increased serum creatinine and total bilirubin. Therefore, a small proportion of patients listed for transplantation with VA ECMO undergo VAD implantation. Their waitlist survival is better than non-VAD group but with similar post-transplant survival.

A Comprehensive Imaging Approach to Guide the Management of Patients with Continuous-Flow Left Ventricular Assist Devices.

Recent advances in mechanical circulatory support have allowed patients with end-stage heart failure to be successfully bridged to heart transplantation or live for many years on continuous-flow left ventricular assist devices (CF-LVADs) as destination therapy. As survival and quality of life continue to improve and the number of patients supported by CF-LVADs continues to grow, utilization of different imaging modalities in the care for these patients has become an integral part of many heart failure centers. We review currently available imaging modalities, with a focus on echocardiography, that aid to diagnose and manage common adverse events associated with CF-LVADs.

Reticulated Platelets: Changing Focus from Basics to Outcomes.

Platelets play an essential role in the pathophysiology of atherothrombosis. Reticulated platelets (RPs) are the youngest platelet population in the circulation; their presence is an indicator of platelet turnover. Circulating levels of RPs are increased in patients with coronary artery disease and stroke. Preliminary indications are that the proportion of circulating RP is associated with the likelihood of ischaemic events such as acute coronary syndrome and stroke. Plausible mechanisms include: (1) increased participation of these platelets in thrombosis due to messenger ribonucleic acid that may be translated to active proteins, (2) lack of exposure to anti-platelet drugs since they are newly released from the bone marrow or (3) their presence is a non-specific marker of inflammation. In this state-of-the-art review, we discuss the implication of RP in coronary artery disease and in hypo-responsiveness to the most commonly used anti-platelet drugs.

Recent advances in heart failure.

PURPOSE OF REVIEW: Acute heart failure continues to be a challenge as there is limited benefit of numerous agents that have been tested. Cardiac resynchronization therapy remains standard of care, yet timing and need for implantable cardiac defibrillator has been brought into question with the recent randomized trials. Several recent advances have been made towards management of heart failure both in drug and device therapy. The purpose of this review is to provide an update on the most important recent studies on heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). RECENT FINDINGS: Two new drugs have been added to the armamentarium for HFrEF; ivabradine and angiotensin receptor-neprilysin inhibitors (ARNIs). Initial data from a new left ventricular assist device (LVAD) pump, the HeartMate 3 (HM III), have demonstrated no reports of pump thrombosis at 6 months, but stroke and right ventricle failure continue to be a challenge with comparable rates compared with the HeartMate II. Several large studies in HFpEF failed to show improvement in outcomes and management continues to be geared towards lifestyle modification and symptom relief. SUMMARY: Newer therapies and devices have met with great success, yet there are several therapies that provide no benefit and even harm. A careful review of the recent literature remains instrumental to the effective management of patients with heart failure.

Exercise And Heart Failure: Advancing Knowledge And Improving Care.

Exercise limitation is the hallmark of heart failure, and an increasing degree of intolerance is associated with poor prognosis. Objective evaluation of functional class (e.g., cardiopulmonary exercise testing) is essential for adequate prognostication in patients with advanced heart failure and for implementing an appropriate exercise training program. A graded exercise program has been shown to be beneficial in patients with heart failure and has become an essential component of comprehensive cardiac rehabilitation in these patients. An exercise program tailored to the patient's preferences, possibilities, and physiologic reserve has the greatest chance of being successful. Despite being safe, effective, and a guideline-recommended treatment to improve quality of life, exercise training remains grossly underutilized. Patient, physician, insurance and practice barriers need to be addressed to improve this quality gap.

Renal Denervation: Past, Present, and Future.

Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide. It is estimated that 12.8% of hypertensive adults have resistant hypertension. The sympathetic nervous system is a well-known contributor to the pathophysiology of resistant hypertension. Renal denervation has emerged as an effective procedure to treat resistant hypertension by blocking the sympathetic nervous system. The medical device industry has developed various catheters in an effort to achieve better denervation in the absence of available testing to document adequate denervation. By adding a sham control group to the study design, researchers found that the results of the Renal Denervation in Patients With Uncontrolled Hypertension study (SYMPLICITY HTN-3) showed that renal denervation was not superior to placebo in decreasing systolic blood pressure. Although SYMPLICITY HTN-3 successfully addressed many issues that might have biased the previously published data, incomplete denervation caused by limited operator experience, catheter design, and the radiofrequency ablation technology may have accounted for the discrepancy of the results. This, along with differences in the study design and population, should direct future renal denervation studies. This article reviews the available literature and proposes future directions for renal denervation studies. It also provides a detailed comparison of the available catheters and their respective clinical data.

Association of immature platelets with adverse cardiovascular outcomes.

BACKGROUND: Immature platelets are less responsive to the effects of antiplatelet drugs and contain messenger ribonucleic acid that is translationally active. They can be measured easily using an automated hematoanalyzer and reported as part of the complete blood count. OBJECTIVES: The purpose of this study was to determine the prognostic significance of elevated immature platelet count (IPC) in patients with coronary artery disease (CAD). METHODS: In this prospective cohort study in patients with CAD, patients underwent IPC measurement and were then followed up for the composite endpoint of major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, myocardial infarction, unplanned revascularization, or hospitalization for angina. For the purposes of analysis, patients were stratified into tertiles of IPC. RESULTS: Eighty-nine patients were followed up for a median of 31 months. Stratification to the high IPC tertile was associated with higher rates of MACE compared with the intermediate and low tertiles (60% vs. 24% vs. 16%, respectively; p < 0.001). Time-dependent receiver-operating characteristic analysis revealed that an IPC level ≥7,632 platelets/µl was 70.7% sensitive and 82.1% specific for MACE. After adjustment for age, admission diagnosis, index revascularization, heart failure, smoking, hematocrit, and baseline platelet count, patients with an IPC level ≥7,632 platelets/µl were more likely to experience a MACE (hazard ratio: 4.65; 95% confidence interval: 1.78 to 12.16; p < 0.002). CONCLUSIONS: IPC is a novel biomarker for MACE risk stratification in patients with CAD. Future studies should focus on the utilization of this marker for individualized antiplatelet therapy.

Current use of fractional flow reserve: a nationwide survey.

Major medical society guidelines recommend the measurement of fractional flow reserve (FFR) as an aid in choosing percutaneous coronary intervention in patients with stable coronary artery disease. We investigated the measurement of FFR among interventionalists, analyzing operators' attributes and decision-making processes to reveal differences in their applications of FFR and the reasons for those differences. An electronic survey study of 1,089 interventionalists was performed from 2 February through 6 March 2012, yielding 255 responses. Most respondents were >45 years old (58%), worked primarily in a community hospital (59%), and performed 10 to 30 cases per month (52%). More than half (145/253, 57%) used FFR measurement in less than one third of cases, and 39 of 253 (15%) never used it. There were no differences in use of FFR by age, practice location, or angiogram volume (P >0.05 for all). Respondents used FFR measurement more frequently than intravascular ultrasonography (73% vs 60%) to help guide the decision to stent (P <0.01). Operators reported that their primary reasons for not using FFR were lack of availability (47%) and problems with reimbursement (39%). There was no difference in FFR use by operator age, practice setting, or case volume.

Stroke-associated pneumonia: major advances and obstacles.

BACKGROUND: Stroke-associated pneumonia (SAP) has been implicated in the morbidity, mortality and increased medical cost after acute ischemic stroke. The annual cost of SAP during hospitalization in the United States approaches USD 459 million. The incidence and prognosis of SAP among intensive care unit (ICU) patients have not been thoroughly investigated. We reviewed the pathophysiology, microbiology, incidence, risk factors, outcomes and prophylaxis of SAP with special attention to ICU studies. METHODS: To determine the incidence, risk factors and prognosis of acute SAP, PubMed was searched using the terms 'pneumonia' AND 'neurology intensive unit' and the MeSH terms 'stroke' AND 'pneumonia'. Non-English literature, case reports and chronic SAP studies were excluded. Studies were classified into 5 categories according to the setting they were performed in: neurological intensive care units (NICUs), medical intensive care units (MICUs), stroke units, mixed studies combining more than one setting or when the settings were not specified and rehabilitation studies. RESULTS: The incidences of SAP in the following settings were: NICUs 4.1-56.6%, MICUs 17-50%, stroke units 3.9-44%, mixed studies 3.9-23.8% and rehabilitation 3.2-11%. The majority of NICU and MICU studies were heterogeneous including different neurovascular diseases, which partly explains the wide range of SAP incidence. The higher incidence in the majority of ICU studies compared to stroke units or acute floor studies is likely explained by the presence of mechanical ventilation, higher stroke severity causing higher rates of aspiration and stroke-induced immunodepression among ICU patients. The short-term mortality of SAP was increased among the mixed and stroke unit studies ranging between 10.1 and 37.3%. SAP was associated with worse functional outcome in the majority of stroke unit and floor studies. Mortality was less consistent among NICU and MICU studies. This difference could be due to the heterogeneity of ICU studies and the effect of small sample size or other independent risk factors for mortality such as the larger neurological deficit, mechanical ventilation, and age, which may simultaneously increase the risk of SAP and mortality confounding the outcomes of SAP itself. The pathophysiology of SAP is likely explained by aspiration combined with stroke-induced immunodepression through complex humeral and neural pathways that include the hypothalamic-pituitary-adrenal axis, parasympathetic and sympathetic systems. CONCLUSIONS: A unified definition of SAP, strict inclusion criteria, and the presence of a long-term follow-up need to be applied to the future prospective studies to better identify the incidence and prognosis of SAP, especially among ICU patients.

Pressure wire used to measure gradient in chronic mesenteric ischemia.

Chronic mesenteric ischemia is a rare disorder in the United States. Frequently, its symptoms correlate poorly with the angiographically apparent degree of mesenteric artery stenosis. Measuring the pressure gradient with a small-caliber catheter is an established means of determining whether a particular stenosis is flow-limiting, thus guiding the interventional decision when stenoses are of indeterminate angiographic significance. Using a 0.014-in guidewire, however, is potentially more accurate because it eliminates any measurement error attributable to the use of a larger, potentially obstructive catheter. We present a case of chronic mesenteric ischemia in a 70-year-old woman who had abdominal pain with multiple possible causes. We used a 0.014-in pressure wire to calculate pressure gradients and guide our decision to stent tandem lesions in the superior mesenteric artery. After revascularization, the patient's symptoms improved dramatically. To the best of our knowledge, this is the first published case in which a pressure wire was used to measure a pressure gradient in chronic mesenteric ischemia.