Central sleep apnea and exposure to ambient hydrogen sulfide emissions from massive strandings of decomposing sargassum in the Caribbean.

BACKGROUND: Sargassum invasion of Caribbean and American shorelines is a recurring environmental hazard. Potential health effects of long-term chronic exposure to sargassum gaseous emissions, notably hydrogen sulfide (H2S), are overlooked. H2S plays an important role in neurotransmission and is involved in generating and transmitting respiratory rhythm. Central sleep apnea (CSA) has been attributed to the depression of respiratory centers. OBJECTIVE: Evaluate the effects of exposure to sargassum-H2S on CSA. METHODS: This study, set in the Caribbean, describes the clinical and polysomnographic characteristics of individuals living and/or working in areas impacted by sargassum strandings, in comparison with non-exposed subjects. Environmental exposure was estimated by the closest ground H2S sensor. Multivariate linear regression was applied to analyze CSA changes according to cumulative H2S exposure over time. Effects of air pollution and other sargassum toxic compounds (NH3) on CSA were also controlled. RESULTS: Among the 685 study patients, 27 % were living and/or working in sargassum impacted areas. Compared with non-exposed patients, exposed ones had similar sleep apnea syndrome risk factors, but had increased levels of CSA events (expressed as absolute number or % of total sleep apnea). Multivariate regression retained only male gender and mean H2S concentration over a 6-month exposure period as independent predictors of an increase in CSA events. A minimal exposure length of 1 month generated a significant rise in CSA events, with the latter increasing proportionally with a cumulative increase in H2S concentration over time. CONCLUSION: This pioneer work highlights a potential effect of sargassum-H2S on the central nervous system, notably on the modulation of the activity of the brain's respiratory control center. These observations, jointly with previous studies from our group, constitute a body of evidence strongly supporting a deleterious effect of sargassum-H2S on the health of individuals chronically exposed to low to moderate concentration levels over time.

Infant congenital heart disease prevalence and mortality in French Guiana: a population-based study.

Background: Few studies have assessed the prevalence and mortality of simple or complex congenital heart diseases (CHD) in newborns. In Latin America and Caribbean (LAC), CHD epidemiology seems highly variable, with few population-based assessments and different methodologies between studies. To date, the situation in French Guiana, a French overseas territory located in South America between Brazil and Suriname, has never been described. Methods: We analysed CHD prevalence, characteristics and related infant mortality in French Guiana, with a population-based registry analysis of all fetal and live birth CHD cases in infants under 1 year (January 2012-December 2016). Findings: Overall, 33,796 births (32,975 live births) were registered, with 231 CHD (56 fetuses), including 215 live births. Most frequent CHD categories were anomalies of the ventricular outflow tract and extra-pericardial trunks, and ventricular septal defects. 18.6% (43/231) chromosomal or genetic anomalies, and 6.5% (15/231) terminations of pregnancy were observed. Total CHD prevalence was 68.4 [95% CI: 67.9-68.8] per 10,000, while live birth prevalence was 65.2 [95% CI: 64.7-65.7] per 10,000. Total infant mortality was 9.4/10,000 live births [95% CI 9.1-9.7], with highest rates for functionally univentricular hearts (FUH). Interpretation: A distinct profile for CHD is highlighted in French Guiana with elevated mortality linked to FUH. A potential determinant of the recognized excess mortality risk might be the presence of chromosomal or genetic anomalies in about a fifth of all CHD. This helps us to better understand CHD burden in this part of South America and provides future keys towards reducing CHD-related infant mortality. Funding: The authors received no financial support for the present research, authorship, and/or publication of this article.

Increased Binding of von Willebrand Factor to Sub-Endothelial Collagen May Facilitate Thrombotic Events Complicating Bothrops lanceolatus Envenomation in Humans.

Consumption coagulopathy and hemorrhagic syndrome exacerbated by blood anticoagulability remain the most important causes of lethality associated with Bothrops snake envenomation. Bothrops venom also engages platelet aggregation on the injured endothelium via von Willebrand factor (vWF) interactions. Besides platelet aggregation, some Bothrops venom toxins may induce qualitative thrombopathy, which has been in part related to the inhibition of vWF activation. We tested whether B. lanceolatus venom impaired vWF to collagen(s) binding (vWF:CB) activity. Experiments were performed with B. lanceolatus crude venom, in the presence or absence of Bothrofav, a monospecific B. lanceolatus antivenom. Venom of B. lanceolatus fully inhibited vWF to collagen type I and III binding, suggesting venom interactions with the vWF A3 domain. In contrast, B. lanceolatus venom increased vWF to collagen type VI binding, suggesting the enhancement of vWF binding to collagen at the vWF A1 domain. Hence, B. lanceolatus venom exhibited contrasting in vitro effects in terms of the adhesive properties of vWF to collagen. On the other hand, the antivenom Bothrofav reversed the inhibitory effects of B. lanceolatus venom on vWF collagen binding activity. In light of the respective distribution of collagen type III and collagen type VI in perivascular connective tissue and the sub-endothelium, a putative association between an increase in vWF:CB activity for collagen type VI and the onset of thrombotic events in human B. lanceolatus envenomation might be considered.

Risk Stratification in Transthyretin Cardiac Amyloidosis: The Added Value of Lung Spirometry.

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. Traditionally, biological staging systems are used to stratify disease severity. Reduced aerobic capacity has recently been described as useful in identifying higher risk of cardiovascular events and death. Assessment of lung volume via simple spirometry might also hold prognostic relevance. We aimed to assess the combined prognostic value of spirometry, cardiopulmonary exercise testing (CPET) and biomarker staging in ATTR-CA patients in a multi-parametric approach. We retrospectively reviewed patient records with pulmonary function and CPET testing. Patients were followed until study endpoint (MACE: composite of heart-failure-related hospitalization and all-cause death) or censure (1 April 2022). In total, 82 patients were enrolled. Median follow-up was 9 months with 31 (38%) MACE. Impaired peak VO2 and forced vital capacity (FVC) were independent predictors of MACE-free survival, with peak VO2 < 50% and FVC < 70% defining the highest risk group (HR 26, 95% CI: 5-142, mean survival: 15 months) compared to patients with the lowest risk (peak VO2 ≥ 50% and FVC ≥ 70%). Combined peak VO2, FVC and ATTR biomarker staging significantly improved MACE prediction by 35% compared to ATTR staging alone, with 67% patients reassigned a higher risk category (p < 0.01). In conclusion, combining functional and biological markers might synergistically improve risk stratification in ATTR-CA. Integrating simple, non-invasive and easily applicable CPET and spirometry in the routine management of ATTR-CA patients might prove useful for improved risk prediction, optimized monitoring and timely introduction of newer-generation therapies.

Determinants of ventilatory inefficiency in transthyretin cardiac amyloidosis: The role of excessive ventilatory drive.

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase. Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included. Results: Compared with CA patients without ventilatory inefficiency (VE-VCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope ≥ 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (ß = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency. Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response.

Cerebral Ischemic Events: An Overlooked Complication of Transthyretin Cardiac Amyloidosis in Afro-Caribbean Patients.

Aim: The link between transthyretin cardiac amyloidosis (CATTR), and cerebral ischemic events (CIE) has only been hinted at till now, impeding progress in patient management. We seek to evaluate the frequency and characteristics of CIE in Afro-Caribbean patients followed for CATTR at our institution. Methods: In this single-center retrospective observational study, Afro-Caribbean patients followed for CATTR between July 2005 and October 2019 were included. Occurrence of CIE was investigated, and their cardioembolic origin determined. Analysis of patient characteristics was conducted according to CIE and CATTR profiles. Results: Overall, 120 CATTR patients were included: 17 wild-type ATTR (14.2%), 73 ATTR-V122I (60.8%), and 22 ATTR-I107V (18.3%). Thirty-six patients (30.0%) presented with CIE, including three transient ischemic attacks and 33 permanent ischemic strokes (75.8% with a cardioembolic pattern). CIE was concomitant with CATTR diagnosis in 16 (16/36: 44.4%) patients, while 14 patients (14/36: 38.9 %) experienced CIE over a median CATTR follow-up of 2.0 years (min-max range: 0.8-4.4 years). CATTR-CIE patients presented with atrial fibrillation (66.7%), left atrial enlargement (77.8%), a CHA2DS2-VASc ≥ 3 (97.2%) and a high anticoagulant intake (75.0%). Multivariate analysis retained only a high CHA2DS2-VASc score as an independent predictor of CIE risk (Hazard Ratio [95% CI]: 12.03 [1.62-89.24]). Conclusion: Concomitant CIE, and CATTR diagnosis, potentially carries a worse prognosis. A CHA2DS2-VASc score ≥3 seems to be a strong and independent predictive factor of CIE in CATTR patients. Further studies are needed to assess the efficacy and timeliness of anticoagulation in CATTR patients, independently of atrial fibrillation.

Risk of preeclampsia among women living in coastal areas impacted by sargassum strandings on the French Caribbean island of Martinique.

OBJECTIVE: To investigate preeclampsia risk of pregnant women living in coastal areas regularly impacted by massive sargassum strandings. DESIGN: Retrospective cohort study SETTINGS AND POPULATION: Pregnant women (n = 3020), seen at the University Hospital of Martinique, were included between 25/01/2016 and 31/07/2020. METHODS: Patient records were retrospectively reviewed. Distance from coastline sargassum stranding sites was characterized as follows: < 500 m, 500 m-2 km, > 2 km. MAIN OUTCOME MEASURES: Primary endpoint was occurrence of preeclampsia. Secondary endpoint was time to preeclampsia defined as the number of weeks free of preeclampsia between the 20th and 37th week of amenorrhea. RESULTS: Time to preeclampsia onset was significantly shorter in women living in the ≤ 2 km range (mean survival time 32 ± 1 amenorrhea weeks) compared to those beyond 2 km (mean survival time 35 ± 1 amenorrhea weeks, p = 0.037). CONCLUSION: Along with traditional risk factors, environmental exposure to sargassum strandings might potentially trigger early onset of preeclampsia.

Diagnostic and Prognostic Values of Cardiopulmonary Exercise Testing in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart, resulting in increased myocardial stiffness, and restrictive heart wall chamber behavior. Its diagnosis among patients hospitalized for cardiovascular diseases is becoming increasingly frequent, suggesting improved disease awareness, and higher diagnostic capacities. One predominant functional manifestation of patients with CA is exercise intolerance, objectified by reduced peak oxygen uptake (VO2 peak), and assessed by metabolic cart during cardiopulmonary exercise testing (CPET). Hemodynamic adaptation to exercise in patients with CA is characterized by low myocardial contractile reserve and impaired myocardial efficiency. Rapid shallow breathing and hyperventilation, in the absence of ventilatory limitation, are also typically observed in response to exercise. Ventilatory inefficiency is further suggested by an increased VE-VCO2 slope, which has been attributed to excessive sympathoexcitation and a high physiological dead space (VD/VT) ratio during exercise. Growing evidence now suggests that, in addition to well-established biomarker risk models, a reduced VO2 peak is potentially a strong and independent predictive factor of adverse patient outcomes, both for monoclonal immunoglobulin light chain (AL) or transthyretin (ATTR) CA. Besides generating prognostic information, CPET can be used for the evaluation of the impact of therapeutic interventions in patients with CA.

Case Report: Pulmonary Leptospirosis Misdiagnosed as COVID-19.

We report the case of an 83-year-old woman with acute, febrile respiratory failure resulting from interstitial pneumonia that required high-flow oxygen therapy. This clinical picture, associated with the ongoing epidemiological situation, initially guided us toward a diagnosis of COVID-19. Based on SARS-CoV-2 reverse transcription-polymerase chain reaction negativity and the absence of anti-SARS-CoV-2 antibodies, a search for a differential diagnosis was conducted that led us to conclude a diagnosis of severe pulmonary leptospirosis This case highlights the need to engage in early discussions about differential diagnoses, including neglected tropical and subtropical diseases, during the COVID-19 era.

Pulmonary 99mTc-HMDP uptake correlates with restrictive ventilatory defects and abnormal lung reactance in transthyretin cardiac amyloidosis patients.

BACKGROUND: Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify 99mTc-hydroxy methylene diphosphonate (HMDP) lung retention in hereditary transthyretin (ATTRv) cardiac amyloidosis patients and to relate tracer uptake intensity to pulmonary function and aerobic capacity. METHODS: We prospectively enrolled 20 patients with biopsy-proven ATTRv cardiac amyloidosis and 20 control subjects. Cardiac involvement was confirmed by echocardiography and nuclear imaging using 99mTc-HMDP. Semi-quantitative analysis of the heart, rib and lung retention was assessed using a simple region of interest technique. Pulmonary function was evaluation by the means of whole-body plethysmography, diffusing capacity of the lung for carbon monoxide, forced oscillation technique and cardiopulmonary exercise testing. RESULTS: Pulmonary tracer uptake estimated by lung to rib retention ratio was higher in ATTRv amyloidosis patients compared with control subjects: median 0.62 (0.55-0.69) vs 0.51 (0.46-0.60); p = 0.014. Analysis of relation between lung 99mTc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (Xrs 5 Hz) and peak VO2, suggesting total lung capacity restriction impaired elastic properties of the lung and poor aerobic capacity. CONCLUSION: Our study suggests that some grade of pulmonary retention of 99mTc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient's lung function and aerobic capacity.

Soluble urokinase plasminogen activator receptor levels are predictive of COVID-19 severity in Afro-Caribbean patients.

Aim: To investigate association between soluble urokinase plasminogen activator receptor (suPAR) plasma levels at admission and incidence of complications in COVID-19 patients. Patients & methods: We considered Afro-Caribbean patients (n = 64) admitted to the hospital between 1 February 2020 and 28 February 2021. Primary outcome was time from the hospital admission until intensive care unit care or death. Results: Primary outcome (hazard ratio, HR [95%CI]) was associated with higher CT scan severity score (3.18 [1.15-8.78], p = 0.025), National Early Warning Score (NEWS2; 1.43 [1.02-2.02], p = 0.041) and suPAR (1.28 [1.06-2.06], p = 0.041). Kaplan-Meier analysis indicated patients with suPAR level above 8.95 ng/ml had a worse outcome (7.95 [3.33-18.97], p < 0.001). Conclusion: Our study suggests that COVID-19 patients with increased baseline suPAR levels are at a high risk of complications.

Plain language summary Our aim was to investigate association between the plasma levels of soluble urokinase plasminogen activator receptor (suPAR) at admission and incidence of complications in COVID-19 patients. Increased suPAR level has been previously associated with activation of inflammation and coagulation, which important features of COVID-19. We considered Afro-Caribbean patients admitted to the hospital between 1 February 2020 and 28 February 2021. Primary outcome was time from the hospital admission until intensive care unit care or death. The use of an integrative prediction tool which combines simple clinical score (NEWS2), imaging technique (chest CT severity score) and suPAR plasma levels has potent predictive value for COVID-19 outcome.

Feasibility of remote technical support for electrophysiological ablation procedures during the current COVID-19 pandemic.

Aims: The treatment of heart rhythm disorders has been significantly impacted by direct consequences of the current COVID-19 pandemic, as well as by restrictions aimed towards constraining viral spread. Methods and results: Usually, catheter ablations of cardiac arrhythmias are guided by electro-anatomic mapping (EAM) systems. Technical staff with medical training, or medical staff with technical training, are needed to assist the operator. Travel restrictions due to the current COVID-19 pandemic have limited the in-person availability of technical support staff. To overcome these limitations, we explored the feasibility of a trans-atlantic remote technical support for EAM, with an internet-based communication platform, for complex electrophysiological ablation procedures. Conclusion: Our first experience, based on nine ablation procedures of different arrhythmias, highlights the feasibility of this approach. Remote support for EAM might therefore facilitate continuous care for patients with arrhythmias during the COVID-19 pandemic, particularly in insular settings. Beyond COVID-19-related challenges, this approach will likely play a greater role in the cardiology field in years to come, due to its significant advantages.

Mental Health of Adolescent Relatives of Intensive Care Patients: Benefits of an Open Visitation Policy.

BACKGROUND: Symptoms of anxiety and depression are common in adolescents with a loved one in an intensive care unit (ICU) and are known precursors of posttraumatic stress disorder (PTSD). OBJECTIVES: To assess the prevalence of PTSD and associated factors in adolescent (age 12-17 years) relatives of patients in an ICU with an open visitation policy. METHODS: One year after the patient was discharged from the ICU, eligible adolescent relatives completed a satisfaction survey, anxiety history questionnaire, and psychometric evaluations (Hospital Anxiety and Depression Scale and 8-item Children's Revised Impact of Event Scale). RESULTS: Thirty-two patients intubated for >2 days and with a Simplified Acute Physiology Score II >30 were included. Forty-six adolescents with first- to third-degree relationships to the patient, and in regular contact (≥monthly) with the patient before hospitalization, were enrolled. The prevalence of PTSD among the adolescents was 33%. Adolescents who visited the ICU were less likely to report feelings of regret than those who did not visit the ICU (2% vs 9%, P = .01). A past sense of threat (odds ratio [95% CI], 19.4 [1.9-201.2]; P = .01) and anxiety and depression symptoms (odds ratio [95% CI], 9.6 [1.4-63.7]; P = .02) were independent factors associated with probable PTSD. CONCLUSIONS: A cautiously prepared open visiting policy should be maintained for adolescents with a relative in the ICU, because it could prevent feelings of regret and subsequent PTSD. Adolescents with risk factors should be screened and followed up.

Sargassum seaweed health menace in the Caribbean: clinical characteristics of a population exposed to hydrogen sulfide during the 2018 massive stranding.

BACKGROUND: Since 2011, there have been ongoing massive unexplained increases of sargassum seaweed strandings along the coastlines of Caribbean countries. The objective of our study was to describe the clinical characteristics of patients exposed to noxious emissions of decomposing sargassum seaweed. METHODS: This observational study included patients from January 2018 to December 2018 for complaints attributed to decomposing sargassum seaweed. History and geographical characteristics of sargassum seaweed strandings as well as detection of ambient air hydrogen sulfide (H2S) levels were documented during the inclusion period. FINDINGS: A total of 154 patients were included. Mean exposure period was 3 months. Neurological (80%), digestive (77%) and respiratory (69%) disorders were the most frequent reasons for medical visit. Temporal distribution of medical visits was related to history of strandings. Geographical origins of patients were consistent with the most impacted areas of strandings as well as the most elevated ambient air H2S levels. INTERPRETATION: The toxicological syndrome induced by sargassum seaweed exposure is close to the toxidrome associated with acute H2S exposure in the range of 0-10 ppm. Our study suggests that patients living in massive stranding areas may be exposed to H2S > 5 ppm for 50 days per year.

Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy.

Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy.Methods and results: Eighteen ATTRv (Val122Ile) patients (72 ± 8-year) and 15 age-matched controls (73 ± 3-year) were prospectively enrolled. Patients' medical records, pulmonary function and cardiopulmonary exercise testing, including non-invasive cardiac hemodynamics and chronotropic response were studied. Compared with age-matched controls, maximal workload (91 ± 8 vs. 65 ± 20 watts) and peak VO2 (19.5 ± 3.0 vs. 14.4 ± 4.1 mL.kg-1.min-1) were lower in ATTRv patients. Despite reaching similar age-predicted maximal HR, ATTRv patients displayed smaller changes in stroke volume (SV) index relative to change in VO2 (49 ± 26 vs. 67 ± 18%). Adequate chronotropic-metabolic index was prevalent in ATTRv patients. HR recovery, as percent decrease in peak HR at 1 and 3-min, was blunded ATTv patients.Conclusions: In Val122Ile ATTRv patients, chronotropic response was appropriate relative to exercise intensity with only few patients displaying CI. HR response to exercise was further characterised by blunted HR recovery in ATTRv patients suggesting lower parasympathetic activity and greater sympathetic stimulation compared with controls.

Infectious Complications Following Snakebite by Bothrops lanceolatus in Martinique: A Case Series.

Infections secondary to snakebite occur in a number of patients and are potentially life-threatening. Bothrops lanceolatus bites in Martinique average 30 cases per year and may result in severe thrombotic and infectious complications. We aimed to investigate the infectious complications related to B. lanceolatus bite. A retrospective single-center observational study over 7 years (2011-2018) was carried out, including all patients admitted to the hospital because of B. lanceolatus bite. One hundred seventy snake-bitten patients (121 males and 49 females) were included. Thirty-nine patients (23%) presented grade 3 or 4 envenoming. Twenty patients (12%) developed wound infections. The isolated bacteria were Aeromonas hydrophila (3 cases), Morganella morganii (two cases), group A Streptococcus, and group B Streptococcus (one case each). Patients were treated empirically with third-generation cephalosporin (or amoxicillin-clavulanate), aminoglycoside, and metronidazole combinations. Outcome was favorable in all patients. The main factor significantly associated with the occurrence of infection following snakebite was the severity of envenoming (P < 0.05). Our findings clearly point toward the frequent onset of infectious complications in B. lanceolatus-bitten patients presenting with grade 3 and 4 envenoming. Thus, based on the bacteria identified in the wounds, we suggest that empiric antibiotic therapy including third-generation cephalosporin should be administered to those patients on hospital admission.