Cardiovascular screening outcomes in the Dutch survivorship care program for Hodgkin lymphoma survivors.

PURPOSE: Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. METHODS: The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. RESULTS: In 186 survivors eligible for cardiovascular screening (mean age 47.8 years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. CONCLUSIONS: Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. IMPLICATIONS FOR CANCER SURVIVORS: Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.

Evaluation of renal function in precarious workers exposed to heavy metals in vulnerable scenarios in the metropolitan area of San Luis Potosí, México.

The aim of the study was to evaluate renal function in three groups of precarious workers: garbage recyclers (REC), quarry workers (CAN), and brick makers (LAD). Samples of urine and blood were collected to evaluate clinical parameters and the metal levels in urine was measured using ICP-MS. REC group had the highest concentrations of chromium in urine (36.03 ± 27.2 µg/l) compared to CAN and LAD groups. Mercury concentrations were higher in the LAD group (3.7 ± 0.8 µg/l). Additionally, arsenic was detected in both CAN and REC groups (25.4 ± 26.2 and 19.09 ± 16.7 µg/l, respectively), while arsenic concentrations in LAD were higher (47.2 ± 30.8 µg/l). In kidney biomarkers, ß2-microglobulin concentrations were higher in the REC group (87867 ± 115159.5 ng/g UCr). Similarly, cystatin-C concentrations were higher in the REC group (32795.61 ± 34965.8 ng/g UCr). The data suggests that precarious workers are exposed to heavy metals and have elevated protein levels that contribute to kidney damage.

Biomechanical response of ultrathin slices of hypertrophic cardiomyopathy tissue to myosin modulator mavacamten.

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disorder of the heart, but effective treatment options remain limited. Mavacamten, a direct myosin modulator, has been presented as novel pharmacological therapy for HCM. The aim of this study was to analyze the biomechanical response of HCM tissue to Mavacamten using living myocardial slices (LMS). LMS (n = 58) from patients with HCM (n = 10) were cultured under electromechanical stimulation, and Verapamil and Mavacamten were administered on consecutive days to evaluate their effects on cardiac biomechanics. Mavacamten and Verapamil reduced contractile force and dF/dt and increased time-to-relaxation in a similar manner. Yet, the time-to-peak of the cardiac contraction was prolonged after administration of Mavacamten (221.0 ms (208.8 - 236.3) vs. 237.7 (221.0 - 254.7), p = 0.004). In addition, Mavacamten prolonged the functional refractory period (FRP) (330 ms (304 - 351) vs. 355 ms (313 - 370), p = 0.023) and better preserved twitch force with increasing stimulation frequencies, compared to Verapamil. As such, Mavacamten reduced (hyper-)contractility and prolonged contraction duration of HCM LMS, suggesting a reduction in cardiac wall stress. Also, Mavacamten might protect against the development of ventricular tachyarrhythmias due to prolongation of the FRP, and improve toleration of tachycardia due to better preservation of twitch force at tachycardiac stimulation frequencies.

Understanding the Oxidative Properties of Nickel Oxyhydroxide in Alcohol Oxidation Reactions.

The NiOOH electrode is commonly used in electrochemical alcohol oxidations. Yet understanding the reaction mechanism is far from trivial. In many cases, the difficulty lies in the decoupling of the overlapping influence of chemical and electrochemical factors that not only govern the reaction pathway but also the crystal structure of the in situ formed oxyhydroxide. Here, we use a different approach to understand this system: we start with synthesizing pure forms of the two oxyhydroxides, ß-NiOOH and γ-NiOOH. Then, using the oxidative dehydrogenation of three typical alcohols as the model reactions, we examine the reactivity and selectivity of each oxyhydroxide. While solvent has a clear effect on the reaction rate of ß-NiOOH, the observed selectivity was found to be unaffected and remained over 95% for the dehydrogenation of both primary and secondary alcohols to aldehydes and ketones, respectively. Yet, high concentration of OH- in aqueous solvent promoted the preferential conversion of benzyl alcohol to benzoic acid. Thus, the formation of carboxylic compounds in the electrochemical oxidation without alkaline electrolyte is more likely to follow the direct electrochemical oxidation pathway. Overoxidation of NiOOH from the ß- to γ-phase will affect the selectivity but not the reactivity with a sustained >95% conversion. The mechanistic examinations comprising kinetic isotope effects, Hammett analysis, and spin trapping studies reveal that benzyl alcohol is oxidatively dehydrogenated to benzaldehyde via two consecutive hydrogen atom transfer steps. This work offers the unique oxidative and catalytic properties of NiOOH in alcohol oxidation reactions, shedding light on the mechanistic understanding of the electrochemical alcohol conversion using NiOOH-based electrodes.

Influence of chronic kidney disease and other risk factors pre-heart transplantation on malignancy incidence post-heart transplantation.

Aims: Chronic kidney disease (CKD) pre-heart transplantation (HTx) has been proposed as a risk factor for malignancy risk post-HTx. Using multicenter registry data, our aim was to calculate the death-adjusted annual incidence of malignancies post-HTx, corroborate the association between CKD pre-HTx and malignancy risk post-HTx, and determine other risk factors for post-HTx malignancies. Methods and materials: We used data from patients transplanted in North American HTx centers between January 2000 and June 2017 and registered in the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry. We excluded recipients with missing data on post-HTx malignancies, heterotopic heart transplant, retransplantation, multi-organ transplantation, and patients with a total artificial heart pre-HTx. Results: Overall, 34,873 patients were included to determine the annual incidence of malignancies, 33,345 patients were included in the risk analyses. The incidence of any malignancy, solid-organ malignancy, post-transplant lymphoproliferative disease (PTLD), and skin cancer adjusted for death 15 years post-HTx, was 26.6%, 10.9%, 3.6%, and 15.8% respectively. Besides widely acknowledged risk factors, CKD stage ≥4 pre-HTx was associated with the development of all malignancies post-HTx (HR 1.17 compared to CKD stage 1, p = 0.023), as well as solid-organ malignancies (HR 1.35, p = 0.01), but not for PTLD (HR 0.73, p = 0.057), and skin cancer (HR 1.06, p = 0.59). Conclusion: Risk of malignancy post-HTx remains high. CKD stages ≥4 pre-HTx was associated with an increased risk for any malignancy and solid-organ malignancy post-HTx. Strategies to mitigate the impact of pre-HTx patient factors on the risk of post-HTx malignancy are needed.

Risk Factors for Immune Checkpoint Inhibitor-Mediated Cardiovascular Toxicities.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) have improved the field of cancer, especially in patients with advanced malignancies. Nevertheless, cardiovascular immune-related adverse events (irAEs) with high mortality and morbidity have been observed, including myocarditis, pericarditis, and vasculitis. To date, only a few clinical risk factors have been described and are currently being investigated. RECENT FINDINGS: In this review, we address the four most prevailing risk factors for cardiovascular irAEs. ICI combination therapy is a predominant risk factor for developing ICI-mediated myocarditis. Additionally, ICI combined with other anti-cancer treatments (e.g., tyrosine kinase inhibitors, radiation, chemotherapy) seems to increase the risk of developing cardiovascular irAEs. Other risk factors include female sex, pre-existing cardiovascular disease, and specific tumors, on which we will further elaborate in this review. An a priori risk strategy to determine who is at risk to develop these cardiovascular irAEs is needed. Insights into the impact of risk factors are therefore warranted to help clinicians improve care and disease management in these patients.

The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant.

In this study, we aim to elucidate the clinical impact and long-term course of tricuspid regurgitation (TR), taking into account its dynamic nature, after biatrial orthotopic heart transplant (OHT). All consecutive adult patients undergoing biatrial OHT (1984-2017) with an available follow-up echocardiogram were included. Mixed-models were used to model the evolution of TR. The mixed-model was inserted into a Cox model in order to address the association of the dynamic TR with mortality. In total, 572 patients were included (median age: 50 years, males: 74.9%). Approximately 32% of patients had moderate-to-severe TR immediately after surgery. However, this declined to 11% on 5 years and 9% on 10 years after surgery, adjusted for survival bias. Pre-implant mechanical support was associated with less TR during follow-up, whereas concurrent LV dysfunction was significantly associated with more TR during follow-up. Survival at 1, 5, 10, 20 years was 97% ± 1%, 88% ± 1%, 66% ± 2% and 23% ± 2%, respectively. The presence of moderate-to-severe TR during follow-up was associated with higher mortality (HR: 1.07, 95% CI (1.02-1.12), p = 0.006). The course of TR was positively correlated with the course of creatinine (R = 0.45). TR during follow-up is significantly associated with higher mortality and worse renal function. Nevertheless, probability of TR is the highest immediately after OHT and decreases thereafter. Therefore, it may be reasonable to refrain from surgical intervention for TR during earlier phase after OHT.

Acute Biomechanical Effects of Empagliflozin on Living Isolated Human Heart Failure Myocardium.

PURPOSE: Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients. METHODS: Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters. RESULTS: Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively). CONCLUSION: The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.

Evaluation of Routine Ear, Nose, and Throat Screening in Heart Transplant Candidates: A Retrospective Cohort Study.

BACKGROUND: Patients with end-stage heart failure refractory to medication can be treated with a heart transplant (HTx). These patients are subjected to a preoperative screening procedure according to International Society for Heart and Lung Transplantation guidelines. Additionally, in our hospital, a routine ear, nose, and throat (ENT) screening is performed, directed toward the identification of asymptomatic infections and head and neck neoplasms. There are no studies demonstrating that this screening has additional value in these patients. METHODS: To investigate the yield of protocolled ENT screening in candidates for HTx, we retrospectively reviewed the medical records of patients who were subjected to the screening procedure between 2012 and 2020. RESULTS: The study population consisted of 251 patients of whom 177 (70.5%) were male with a median age of 52 years (IQR, 45-59 years). Ten patients (4.0%) were diagnosed with an infection (sinus) or a neoplasm, resulting in a number needed to screen of 25. In all cases, ENT consultation or sinus radiography did not influence the decision to list patients for HTx. Furthermore, no major ENT infections or occurrence of de novo head and neck malignant neoplasm were observed during follow-up after HTx. CONCLUSIONS: The clinically relevant yield of protocolled ENT screening in candidates for HTx is low. Based on these findings, we believe that only patients with abnormal findings on a routine sinus computed tomography scan and/or specific ENT complaints should be referred to an otorhinolaryngologist.

Future steps in cardio-oncology-a national multidisciplinary survey among healthcare professionals in the Netherlands.

BACKGROUND: The awareness of cancer therapy-related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice. MATERIAL AND METHODS: A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media. RESULTS: One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms' cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (N = 46; 69.7%), radiation oncologists (N = 45; 68.2%), and hematologists and medical oncologists (N = 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic. CONCLUSION: The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients.

The Dutch national paediatric heart transplantation programme: outcomes during a 23-year period.

BACKGROUND: Since 1998, there has been a national programme for paediatric heart transplantations (HT) in the Netherlands. In this study, we investigated waiting list mortality, survival post-HT, the incidence of common complications, and the patients' functional status during follow-up. METHODS: All children listed for HT from 1998 until October 2020 were included. Follow-up lasted until 1 January 2021. Data were collected from the patient charts. Survival, post-operative complications as well as the functional status (Karnofsky/Lansky scale) at the end of follow-up were measured. RESULTS: In total, 87 patients were listed for HT, of whom 19 (22%) died while on the waiting list. Four patients were removed from the waiting list and 64 (74%) underwent transplantation. Median recipient age at HT was 12.0 (IQR 7.2-14.4) years old; 55% were female. One-, 5­, and 10-year survival post-HT was 97%, 95%, and 88%, respectively. Common transplant-related complications were rejections (50%), Epstein-Barr virus infections (31%), cytomegalovirus infections (25%), post-transplant lymphoproliferative disease (13%), and cardiac allograft vasculopathy (13%). The median functional score (Karnofsky/Lansky scale) was 100 (IQR 90-100). CONCLUSION: Children who undergo HT have an excellent survival rate up to 10 years post-HT. Even though complications post-HT are common, the functional status of most patients is excellent. Waiting list mortality is high, demonstrating that donor availability for this vulnerable patient group remains a major limitation for further improvement of outcome.

Added value of semi-quantitative analysis of [18F]FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device.

AIMS: Left ventricular assist devices (LVADs) improve quality of life and survival in patients with advanced heart failure, but device-related infections (DRIs) remain cumbersome. We evaluated the diagnostic capability of [18F]FDG PET/CT, factors affecting its accuracy, and the additive value of semi-quantitative analysis for the diagnosis of DRI. METHODS AND RESULTS: LVAD recipients undergoing [18F]FDG PET/CT between 2012 and 2020 for suspected DRI were retrospectively included. [18F]FDG PET/CT was performed and evaluated in accordance with EANM guidelines. The final diagnosis of DRI, based on multidisciplinary consensus and findings during surgery, whenever performed, was used as the reference for diagnosis. 41 patients were evaluated for 59 episodes of suspected DRI. The clinical evaluation established driveline infection in 32 (55%) episodes, central device infection in 6 (11%), and combined infection in 2 (4%). Visual analysis of [18F]FDG PET/CT achieved a sensitivity and specificity for driveline infections of 0.79 and 0.71, respectively, whereas semi-quantitative analysis achieved a sensitivity and specificity of 0.94 and 0.83, respectively. For central device component infection, visual analysis of [18F]FDG PET/CT achieved a sensitivity and specificity of 0.75 and 0.60, respectively. Semi-quantitative analysis using SUVratio achieved a sensitivity and specificity of 1.0 and 0.8, respectively. The increase of specificity for central component infection was statistically significant (P = 0.05). CONCLUSIONS: [18F]FDG PET/CT reliably predicts the presence of DRI in LVAD recipients. Semi-quantitative analysis may increase the specificity of [18F]FDG PET/CT for the analysis of central device component infection and should be considered in equivocal cases after visual analysis.

Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.

BACKGROUND: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. METHODS: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. RESULTS: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). CONCLUSIONS: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. REGISTRATION: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).

Clinical Characteristics and Outcomes of Immunocompromised Patients With Coronavirus Disease 2019 Caused by the Omicron Variant: A Prospective, Observational Study.

BACKGROUND: Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron. METHODS: Organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients infected with the Omicron variant were included. Characteristics of consenting patients were collected and patients were contacted regularly until symptom resolution. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. RESULTS: 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received 3 mRNA vaccinations. While only 1 patient died, 23 (20%) were hospitalized for a median of 11 days. A low SARS-CoV-2 immunoglobulin G (IgG) antibody response (<300 BAU [binding antibody units]/mL) at diagnosis, being older, being a lung transplant recipient, having more comorbidities, and having a higher frailty score were associated with hospital admission (all P < .01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% had a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of these patients, and 1 died. CONCLUSIONS: While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. In addition to vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

Estimating the burden of disease attributable to ambient air pollution (ambient PM2.5 and ambient ozone) in South Africa for 2000, 2006 and 2012.

Background: Globally, a growing body of research has shown that ambient air pollution is one of the most critical environmental issues, especially in relation to human health. Exposure to ambient air pollution leads to serious health conditions such as lower respiratory infections, cancers, diabetes mellitus type 2, ischaemic heart disease, stroke and chronic obstructive pulmonary disease. Objectives: To estimate the burden of disease attributable to ambient air pollution in South Africa (SA) for the years 2000, 2006 and 2012. Methods: Comparative risk assessment method was used to determine the burden of disease due to two pollutants (particulate matter (PM2.5) and ambient ozone). Regionally optimised fully coupled climate chemistry models and surface air pollution observations were used to generate concentrations of PM2.5 and ozone for each SA Census Small Area Level, for the year 2012. For 2000 and 2006, population-weighted PM2.5and ozone were estimated, based on the 2012 results. Following the identification of disease outcomes associated with particulate matter with aerodynamic diameter <2.5 µm (PM2.5) and ozone exposure, the attributable burden of disease was estimated for 2000, 2006 and 2012. Furthermore, for the year 2012, the burden of disease attributable to ambient air pollution exposure was computed at provincial levels. Results: In 2012, approximately 97.6% of people in SA were exposed to PM2.5 at levels above the 2005 World Health Organization guideline: 10 µg/m3 annual mean. From 2000 to 2012, population-weighted annual average PM2.5 increased from 26.6 µg/m3 to 29.7 µg/m3, and ozone 6-month high 8-hour daily maximum increased from 64.4 parts per billion (ppb) to 72.1 ppb. At a national scale, in the year 2000, 15 619 (95% uncertainty interval (UI) 8 958 - 21 849) deaths were attributed to PM2.5 exposure, while 1 326 (95% UI 534 - 1 885) deaths were attributed to ozone. In 2006, an estimated 19 672 deaths (95% UI 11 526 - 27 086) were attributed to PM2.5, and a further 1 591 deaths (95% UI 651 - 2 236) to ozone exposure. In 2012, deaths attributed to PM2.5 were 19 507 (95% UI 11 318 - 27 111), and to ozone 1 734 (95% UI 727 - 2 399). Additionally, population-weighted provincial scale analysis showed that Gauteng Province had the highest number of attributable deaths due to both PM2.5 and ozone in 2012. Conclusion: The study showed that ambient air pollution exposure is an important health risk in SA, requiring both short- and long-term intervention. In the short term, the SA Ambient Air Quality Standards and industrial minimum emissions standards need to be enforced. In the longer term, to reduce air pollution and the associated disease burden, the combustion of fossil fuels as a source of energy for power generation and transportation, as well as industrial and domestic uses, needs to be replaced with clean renewable energy sources. In addition to local measures, when the southern African prevalent anticyclonic air dynamics that transport regionally emitted pollutants into SA (especially from biomass burning) are considered, it is also advisable to establish long-term regional co-operation in reducing air pollution.

Relapsing low-flow alarms due to suboptimal alignment of the left ventricular assist device inflow cannula.

OBJECTIVES: This retrospective study investigated the correlation between the angular position of the left ventricular assist device (LVAD) inflow cannula and relapsing low-flow alarms. METHODS: Medical charts were reviewed of all patients with HeartMate 3 LVAD support for relapsing low-flow alarms. A standardized protocol was created to measure the angular position with a contrast-enhanced computed tomography scan. Statistics were done using a gamma frailty model with a constant rate function. RESULTS: For this analysis, 48 LVAD-supported patients were included. The majority of the patients were male (79%) with a median age of 57 years and a median follow-up of 30 months (interquartile range: 19-41). Low-flow alarm(s) were experienced in 30 (63%) patients. Angulation towards the septal-lateral plane showed a significant increase in low-flow alarms over time with a constant rate function of 0.031 increase in low-flow alarms per month of follow-up per increasing degree of angulation (P = 0.048). When dividing this group using an optimal cut-off point, a significant increase in low-flow alarms was observed when the septal-lateral angulation was 28° or more (P = 0.001). Anterior-posterior and maximal inflow cannula angulation did not show a significant difference. CONCLUSIONS: This study showed an increasing number of low-flow alarms when the degrees of LVAD inflow cannula expand towards the septal-lateral plane. This emphasizes the importance of the LVAD inflow cannula angular position to prevent relapsing low-flow alarms with the risk of diminished quality of life and morbidity.

Relapsing low-flow alarms due to suboptimal alignment of the left ventricular assist device inflow cannula.

OBJECTIVES: This retrospective study investigated the correlation between the angular position of the left ventricular assist device (LVAD) inflow cannula and relapsing low-flow alarms. METHODS: Medical charts were reviewed of all patients with HeartMate 3 LVAD support for relapsing low-flow alarms. A standardized protocol was created to measure the angular position with a contrast-enhanced computed tomography scan. Statistics were done using a gamma frailty model with a constant rate function. RESULTS: For this analysis, 48 LVAD-supported patients were included. The majority of the patients were male (79%) with a median age of 57 years and a median follow-up of 30 months (interquartile range: 19-41). Low-flow alarm(s) were experienced in 30 (63%) patients. Angulation towards the septal-lateral plane showed a significant increase in low-flow alarms over time with a constant rate function of 0.031 increase in low-flow alarms per month of follow-up per increasing degree of angulation (P = 0.048). When dividing this group using an optimal cut-off point, a significant increase in low-flow alarms was observed when the septal-lateral angulation was 28° or more (P = 0.001). Anterior-posterior and maximal inflow cannula angulation did not show a significant difference. CONCLUSIONS: This study showed an increasing number of low-flow alarms when the degrees of LVAD inflow cannula expand towards the septal-lateral plane. This emphasizes the importance of the LVAD inflow cannula angular position to prevent relapsing low-flow alarms with the risk of diminished quality of life and morbidity.

Heart Failure and Pancreas Exocrine Insufficiency: Pathophysiological Mechanisms and Clinical Point of View.

Heart failure is associated with decreased tissue perfusion and increased venous congestion that may result in organ dysfunction. This dysfunction has been investigated extensively for many organs, but data regarding pancreatic (exocrine) dysfunction are scarce. In the present review we will discuss the available data on the mechanisms of pancreatic damage, how heart failure can lead to exocrine dysfunction, and its clinical consequences. We will show that heart failure causes significant impairment of pancreatic exocrine function, particularly in the elderly, which may exacerbate the clinical syndrome of heart failure. In addition, pancreatic exocrine insufficiency may lead to further deterioration of cardiovascular disease and heart failure, thus constituting a true vicious circle. We aim to provide insight into the pathophysiological mechanisms that constitute this reciprocal relation. Finally, novel treatment options for pancreatic dysfunction in heart failure are discussed.

Single-Center Experience With Protocolized Treatment of Left Ventricular Assist Device Infections.

Purpose: Because of the current lack of evidence-based antimicrobial treatment guidelines, Left Ventricular Assist Device (LVAD) infections are often treated according to local insights. Here, we propose a flowchart for protocolized treatment, in order to improve outcome. Methods: The flowchart was composed based on literature, consensus and expert opinion statements. It includes choice, dosage and duration of antibiotics, and indications for suppressive therapy, with particular focus on Staphylococcus aureus (SA) (Figure 1). The preliminary treatment results of 28 patients (2 from start cephalexin suppressive therapy) after implementation in July 2018 are described. Results: Cumulative incidence for first episode of infection in a 3-year time period was 27% (26 of 96 patients with an LVAD). Twenty-one of 23 (91%) first episodes of driveline infection (10 superficial and 13 deep; nine of 13 caused by SA) were successfully treated with antibiotics according to flowchart with complete resolution of clinical signs and symptoms. For two patients with deep driveline infections, surgery was needed in addition. There were no relapses of deep driveline infections, and only 2 SA deep driveline re-infections after 6 months. Nine patients received cephalexin of whom four patients (44%) developed a breakthrough infection with cephalexin-resistant gram-negative bacteria. Conclusions: The first results of this protocolized treatment approach of LVAD infections are promising. Yet, initiation of cephalexin suppressive therapy should be carefully considered given the occurrence of infections with resistant micro-organisms. The long-term outcome of this approach needs to be established in a larger number of patients, preferably in a multi-center setting.