Maternal Inheritance of Familial Hypercholesterolemia Gene Mutation Predisposes to Coronary Atherosclerosis as Assessed by Calcium Score in Adulthood.

BACKGROUND: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis. METHODS: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score. RESULTS: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P<0.0001) and were 2 years older (46.9±16.8 versus 44.7±15.9 years old, P=0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%-170%; P=0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06-3.11; P=0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39-5.51; P=0.004) when compared with paternal inheritance in multivariate analysis. CONCLUSIONS: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.

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.

Cardiovascular phenotypes predict clinical outcomes in sickle cell disease: An echocardiography-based cluster analysis.

This study sought to link cardiac phenotypes in homozygous Sickle Cell Disease (SCD) patients with clinical profiles and outcomes using cluster analysis. We analyzed data of 379 patients included in the French Etendard Cohort. A cluster analyses was performed based on echocardiographic variables, and the association between clusters, clinical profiles and outcomes was assessed. Three clusters were identified. Cluster 1 (n = 123) patients had the lowest cardiac output, mild left cardiac cavities remodeling, mild diastolic dysfunction, and higher tricuspid regurgitation velocity (TRV). They were predominantly female and displayed the most altered functional limitation. Cluster 2 (n = 102) patients had the highest cardiac output and the most remodeled cardiac cavities. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (n = 154) patients had mild left cardiac cavities remodeling, normal diastolic function and lowest TRV values. They were younger with the highest hemoglobin value. Right heart catheterization was performed in 94 patients. Cluster 1 (n = 33) included the majority of pre-capillary PH whilst cluster 2 (n = 34) included post-capillary PH. No PH was found in cluster 3 (n = 27). After a follow-up of 11.4 ± 2 years, death occurred in 41 patients (11%). Cluster 2 patients had the worst prognosis with a 19% mortality rate versus 12% in cluster 1 and 5% in cluster 3 (p log-rank = 0.003). Cluster analysis of echocardiography variables identified three hemodynamic and clinical phenotypes among SCD patients, each predicting a different prognosis.

Covid-19 in the Caribbean: lessons learned from the ongoing international medical and scientific cooperation.

The coronavirus disease (Covid-19) crisis presents as human, social and economic challenges. The advent of Covid-19, unfortunate as it is, has highlighted the need for close medical cooperation between states. Medical cooperation is the key counter to fight against the Covid-19 pandemic.

Diabetes mellitus and obesity in the French Caribbean: A special vulnerability for women?

The objective of this study was to analyze the prevalence, awareness, treatment, and control of diabetes and its risk factors among French Caribbean adults. This cross-sectional study included 18-74-year olds (N = 2252; 56.5 percent women) who underwent a heath examination in Guadeloupe during July-December 2014. Diabetes was defined as using antidiabetic treatment, or fasting glucose ≥7 mmol/l, and glycated hemoglobin (HbA1c) ≥6.5 percent; diabetes control was defined as HbA1c < 7 percent. Multilevel logistic regression was used. Diabetes prevalence was 8.2 percent for women and 5 percent for men (age-adjusted odds ratio [aOR] for women = 2.0; 95 percent confidence interval [CI]: 1.4-2.9). The proportion of women with diabetes who were aware of it was 84.5 versus 67.3 percent in men (aOR = 2.7; 95 percent CI: 1.2-6.2). Nearly, all diagnosed participants were being treated. In less than a third of diabetics in both sexes was diabetes control obtained. Most women (55.3 percent) had a waist circumference at or above the National Cholesterol Education Program thresholds versus 14 percent of men (aOR = 9.3; 95 percent CI: 7.5-11.7), which wholly accounted for excess diabetes in women. In women, obesity and diabetes were associated with low education and income. In this French Caribbean sample, abdominal obesity and diabetes affected more women. Diabetes was rarely controlled. A comprehensive women's health policy for the prevention of abdominal obesity and diabetes is needed.

Haematological determinants of cardiac involvement in adults with sickle cell disease.

AIMS: Cardiac involvement is common in sickle cell disease (SCD). Studies are needed to establish haematological determinants of this involvement and prognostic markers. The aim of the study was to identify haematological factors associated with cardiac involvement in SCD and their impact on prognosis. METHODS AND RESULTS: This longitudinal observational study was performed on 1780 SCD patients with SS or S-ß(0)-thalassemia referred to our centre. Six hundred fifty-six met our inclusion criteria (availability of a blood-workup and echocardiogram obtained <1 year apart, no heart valve surgery and no current pregnancy). Median age was 31 (interquartile range, 25-40) years, and median haemoglobin (Hb) was 87 (80-95)g/L. Left ventricular (LV) dilation, left atrial dilation, cardiac index (CI) >4 L/min/m(2), LV ejection fraction <55%, and tricuspid regurgitant velocity (TRV) ≥2.5 m/s were found in 35, 78, 23, 8.5, and 17% of patients, respectively. Compared with other patients, those in the fourth quartiles (Q4) of LV end-diastolic dimension index (LVEDDind) and left atrial dimension index (LADind) and those with high CI had significantly lower Hb, % foetal Hb (HbF), and red blood cell (RBC) counts; and significantly higher lactate dehydrogenase, bilirubin, and %dense RBCs. Independent haematologic determinants of Q4 LVEDDind and LADind were low RBC count and %HbF; high %dense RBCs were associated with LADind. Low %HbF and RBC count were associated with high CI. High %dense RBCs or no α-thalassemia gene deletion was associated with greater severity of anaemia and cardiac dilation and with higher CI. During the median follow-up of 48 (32-59) months, 50 (7.6%) patients died. Tricuspid regurgitant velocity ≥ 2.5 m/s was a predictor of mortality. The risk of death increased four-fold when left ventricular ejection fraction <55% was present also (P = 0.0001). CONCLUSION: Cardiac dilation and CI elevation in patients with SCD are associated with haematologic variables reflecting haemolysis, RBC rigidity, and blood viscosity. Tricuspid regurgitant velocity ≥ 2.5 and LV dysfunction (even mild) predict mortality.

Perceptions of overweight in a Caribbean population: the role of health professionals.

BACKGROUND: The prevalence of obesity and its complications is particularly high in the Caribbean. Underestimation of weight status could explain the failure by subjects concerned to adopt behaviours complying with medical recommendations. Little research is available on the role of health professionals in overweight perception. OBJECTIVE: To examine relationships between overweight underestimation and lack of communication on overweight diagnosis by health professionals in a multicultural Caribbean population. METHODS: A cross-sectional study, lead in 2014 on a sample representative of the population of Saint-Martin (395 subjects, 25-74 years). Overweight perception was assessed on Likert scale. Corpulence was assessed from measured waist circumference (WC). Individuals with excess abdominal adiposity (WC ≥ 80cm for women, ≥ 94cm for men) but stating they did not feel overweight were considered to underestimate their weight status. Patient-reported lack of communication on their diagnosis by health professionals was likewise explored. Respondents' first language defined cultural community. Multivariate analysis used logistic regression. RESULTS: Among individuals presenting excessive WC, 4 out of 10 did not perceive themselves as overweight. Six out of 10 said they had never been told about their weight by a health professional, whether or not they had their weight and waist measured by their referring physician in the preceding year. Independently from WC, overweight underestimation was associated with lack of communication on overweight diagnosis for both sexes. For women, overweight underestimation was associated with belonging to the Creole community. CONCLUSION: Greater care is required when giving a diagnosis of overweight, particularly in social-cultural contexts where weight norms differ.

Managing acute severe hypertension during coronary angiography: Lessons from a challenging case.

We report the clinical case of a 52-year-old man referred to our catheterization laboratory for an acute coronary syndrome. The coronary angiogram course was soon disrupted by a life-threatening blood pressure chaos lasting for hours. An abdominal paraganglioma was eventually diagnosed, requiring surgery. This case outlines the potential diagnosis and therapeutic missteps in managing such patients and suggests strategies for quick improvement.

Abnormal Mitochondrial cAMP/PKA Signaling Is Involved in Sepsis-Induced Mitochondrial and Myocardial Dysfunction.

Adrenergic receptors couple to Gs-proteins leading to transmembrane adenylyl cyclase activation and cytosolic cyclic adenosine monophosphate (cAMP) production. Cyclic AMP is also produced in the mitochondrial matrix, where it regulates respiration through protein kinase A (PKA)-dependent phosphorylation of respiratory chain complexes. We hypothesized that a blunted mitochondrial cAMP-PKA pathway would participate in sepsis-induced heart dysfunction. Adult male mice were subjected to intra-abdominal sepsis. Mitochondrial respiration of cardiac fibers and myocardial contractile performance were evaluated in response to 8Br-cAMP, PKA inhibition (H89), soluble adenylyl cyclase inhibition (KH7), and phosphodiesterase inhibition (IBMX; BAY60-7550). Adenosine diphosphate (ADP)-stimulated respiratory rates of cardiac fibers were reduced in septic mice. Compared with controls, stimulatory effects of 8Br-cAMP on respiration rates were enhanced in septic fibers, whereas inhibitory effects of H89 were reduced. Ser-58 phosphorylation of cytochrome c oxidase subunit IV-1 was reduced in septic hearts. In vitro, incubation of septic cardiac fibers with BAY60-7550 increased respiratory control ratio and improved cardiac MVO2 efficiency in isolated septic heart. In vivo, BAY60-7550 pre-treatment of septic mice have limited impact on myocardial function. Mitochondrial cAMP-PKA signaling is impaired in the septic myocardium. PDE2 phosphodiesterase inhibition by BAY60-7550 improves mitochondrial respiration and cardiac MVO2 efficiency in septic mice.

A hemodynamic study of pulmonary hypertension in sickle cell disease.

BACKGROUND: The prevalence and characteristics of pulmonary hypertension in adults with sickle cell disease have not been clearly established. METHODS: In this prospective study, we evaluated 398 outpatients with sickle cell disease (mean age, 34 years) at referral centers in France. All patients underwent Doppler echocardiography, with measurement of tricuspid-valve regurgitant jet velocity. Right heart catheterization was performed in 96 patients in whom pulmonary hypertension was suspected on the basis of a tricuspid regurgitant jet velocity of at least 2.5 m per second. Pulmonary hypertension was defined as a mean pulmonary arterial pressure of at least 25 mm Hg. RESULTS: The prevalence of a tricuspid regurgitant jet velocity of at least 2.5 m per second was 27%. In contrast, the prevalence of pulmonary hypertension as confirmed on catheterization was 6%. The positive predictive value of echocardiography for the detection of pulmonary hypertension was 25%. Among the 24 patients with confirmed pulmonary hypertension, the pulmonary-capillary wedge pressure was 15 mm Hg or less (indicating precapillary pulmonary hypertension) in 11 patients. Patients with confirmed pulmonary hypertension were older and had poorer functional capacity and higher levels of N-terminal pro-brain natriuretic peptide than other patients. In contrast, patients who had a tricuspid regurgitant jet velocity of at least 2.5 m per second without pulmonary hypertension and patients with a tricuspid regurgitant jet velocity of less than 2.5 m per second had similar clinical characteristics. CONCLUSIONS: In this study of adults with sickle cell disease, the prevalence of pulmonary hypertension as confirmed on right heart catheterization was 6%. Echocardiographic evaluation alone had a low positive predictive value for pulmonary hypertension. (Funded by the French Ministry of Health and Assistance Publique-Hôpitaux de Paris; ClinicalTrials.gov number, NCT00434902.).

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.

Phenotypic characteristics of F64L, I68L, I107V, and S77Y ATTRv genotypes from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multi-systemic disease with wild-type (ATTRwt) and hereditary (ATTRv) forms. Over 130 variants associated with ATTRv amyloidosis have been identified, although little is known about the majority of these genotypes. This analysis examined phenotypic characteristics of symptomatic patients with ATTRv amyloidosis enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) with four less frequently reported pathogenic genotypes: F64L (c.250T>C, p.F84L), I68L (c.262A>T, p.I88L), I107V (c.379A>G; p.I127V), and S77Y (c.290C>A; p.S97Y). THAOS is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both ATTRwt and ATTRv amyloidosis. This analysis describes the baseline demographic and clinical characteristics of untreated symptomatic patients with the F64L, I68L, I107V, or S77Y genotypes at enrollment in THAOS (data cutoff date: January 4, 2022). There were 141 symptomatic patients with F64L (n = 46), I68L (n = 45), I107V (n = 21), or S77Y (n = 29) variants at the data cutoff. Most patients were male and median age at enrollment was in the sixth decade for S77Y patients and the seventh decade for the others. A predominantly neurologic phenotype was associated with F64L, I107V, and S77Y genotypes, whereas patients with the I68L genotype presented with more pronounced cardiac involvement. However, a mixed phenotype was also reported in a considerable proportion of patients in each variant subgroup. This analysis from THAOS represents the largest study of ATTRv symptomatic patients with the F64L, I68L, I107V, and S77Y genotypes. These data add to the limited knowledge on the clinical profile of patients with specific ATTRv variants and emphasize the importance of comprehensive assessment of all patients. Trial registration ClinicalTrials.gov: NCT00628745.

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity.

Background: The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise. Abnormal exercise pressor reflex response has been associated with exaggerated ventilatory drive, sympathovagal imbalance and exercise limitation in chronic heart failure patients. Whether metaboreflex is over-activated and participate to poor aerobic capacity in patients with hereditary transthyretin cardiac amyloidosis (CA-TTR) is unknown. Methods: Twenty-two CA-TTR patients (aged 76 ± 7, 68% male) with the V122I (p.Val142Ile) transthyretin underwent a thorough evaluation including heart rate variability metrics, electrochemical skin conductance (ESC), physical function cardiopulmonary exercise testing, and muscle metaboreflex assessment. Eleven control subjects were chosen for muscle metaboreflex assessment. Results: Age-matched controls (n = 11) and CA-TTR patients (n = 22) had similar metaboreflex sensitivity for heart rate, stroke volume, cardiac index and mean systemic arterial pressure. Compared with age-matched controls, metaboreflex sensitivity for systemic vascular resistance (-18.64% ± 6.91% vs 3.14% ± 23.35%) and minute-ventilation responses (-9.65% ± 14.83% vs 11.84% ± 23.1%) was markedly increased in CA-TTR patients. Values of ESC displayed positive correlations with stroke volume (r = 0.53, p = 0.011) and cardiac index (r = 0.51, p = 0.015) components of metaboreflex sensitivity, an inverse correlation with systemic vascular resistance (r = -0.55, p = 0.008) and a trend with mean arterial (r = -0.42, p = 0.052) components of metaboreflex sensitivity. Peak aerobic capacity (peak VO2%) displayed an inverse correlation with the ventilation component of metaboreflex sensitivity (r = -0.62, p = 0.015). Conclusion: Consistent with the "muscle hypothesis" in heart failure, it is proposed that deterioration of skeletal muscle function in hereditary CA-TTR patients may activate muscle metaboreflex, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and overall sympathetic activation.

Association between Previous CPAP and Comorbidities at Diagnosis of Obesity-Hypoventilation Syndrome Associated with Obstructive Sleep Apnea: A Comparative Retrospective Observational Study.

Obesity-hypoventilation syndrome (OHS) is associated with many comorbidities. The aim of this study was to evaluate the association between previous continuous positive airway pressure (CPAP) and the prevalence of comorbidities in OHS associated with obstructive sleep apnea (OSA). We performed a retrospective, single-center study at the University Hospital of Martinique, the referral hospital for the island of Martinique. A total of 97 patients with OHS associated with severe OSA on non-invasive ventilation (NIV) were included; 54 patients (56%) had previous treatment of OSA with a positive airway pressure (PAP) device before shifting to NIV (PAP group) and 43 (44%) had no previous treatment of OSA with a PAP device before initiating NIV PAP (no PAP group). Sociodemographic characteristics were similar between groups; there were 40 women (74%) in the PAP group versus 34 (79%) in the no PAP group, mean age at OHS diagnosis was 66 ± 15 versus 67 ± 16 years, respectively, and the mean age at inclusion 72 ± 14 versus 71 ± 15 years, respectively. The average number of comorbidities was 4 ± 1 in the PAP group versus 4 ± 2 in the no PAP group; the mean Charlson index was 5 ± 2 in both groups. The mean BMI was 42 ± 8 kg/m2 in both groups. The mean follow-up duration was 5.8 ± 4.4 years in the PAP group versus 4.7 ± 3.5 years in the no PAP group. Chronic heart failure was less common in patients who had a previous PAP 30% versus 53% (p = 0.02). It is also noted that these patients were diagnosed less often in the context of acute respiratory failure in patients with previous PAP: 56% versus 93% (p < 0.0001). In contrast, asthma patients were more frequent in patients with previous treatment of OSA with a PAP device at the time of OHS diagnosis but not significantly: 37% versus 19% (p = 0.07). Early treatment of severe OSA with a PAP device prior to diagnosis of OHS seems to be associated with a reduced prevalence of cardiac diseases, notably chronic heart failure, in patients diagnosed with OHS associated with severe OSA.

Impact of Previous Continuous Positive Airway Pressure Use on Noninvasive Ventilation Adherence and Quality in Obesity Hypoventilation Syndrome: A Pragmatic Single-Center Cross-Sectional Study in Martinique.

There is a strong relationship between obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). When OHS is combined with severe OSA, treatment consists of continuous positive airway pressure (CPAP), followed by noninvasive ventilation (NIV) in the case of CPAP failure. Currently, the impact of a previous use of CPAP on the quality of NIV is unknown. We conducted a cross-sectional study with OHS patients, to assess the quality of NIV according to previous CPAP use. We included 75 patients with OHS on NIV (65 women, 87%). Among these, 40 patients (53.3%) who had had prior CPAP (CPAP+ group) were compared to the remaining 35 patients (46.7%) (CPAP- group). Key characteristics were comparable between the CPAP+ and the CPAP- groups: age at diagnosis of OHS was 67 ± 3 vs. 66 ± 4 years (p = 0.8), age at inclusion was 73 ± 15 vs. 69 ± 15 years (p = 0.29), number of comorbidities was 3.7 ± 1.2 vs. 3.3 ± 1.5, the Charlson index was 5.1 ± 2 vs. 4.6 ± 1.8, and BMI was 41.6 ± 7.6 kg/m2 vs. 41.2 ± 8.2, respectively, all p > 0.05. Follow-up length was greater in CPAP+ vs. CPAP- patients (5.6 ± 4.2 vs. 2.9 ± 2.9 years, p = 0.001). The quality of NIV based on daily adherence, pressure support, apnea-hypopnea index (AHI) and leaks was similar in both groups. Reduced adherence (less than 4 h daily) was found in 10 CPAP+ patients (25%) versus 7 CPAP- patients (20%), p = 0.80. NIV efficacy was also similar. This study found no difference in the quality of NIV or in adherence between patients who had had prior CPAP and those who had not. Previous CPAP does not appear to improve the quality of NIV.

Frequency and Distribution of Broncho-Alveolar Fungi in Lung Diseases in Martinique.

The microbiota refers to all the microorganisms living in and on the human body; its fungal component is known as the mycobiota. The molecular component (mycobiome) has been linked to certain pulmonary diseases. Morphological fungal examination is still common practice and makes it possible to isolate fungi on direct examination or after sample culture. This study aimed to identify fungi via the genus colonising the respiratory tract in our environment and to evaluate the relationship between identified fungi and underlying diseases. We performed a retrospective study of patients who underwent bronchofiberoscopy and mycological analysis of fluid collected by broncho-alveolar lavage at our centre over a period of 5 years. During the study period, 1588 samples from 1547 patients were analysed (50.7% male, mean age 63.7 ± 14.8 years). Among the 1588 samples, 213 (13.4%) were positive on direct examination, and 1282 (80.8%) were positive after culture. The average number of species detected per sample was 1.4 ± 1.1. For patients with positive fungus, the median was two (ranging from one to seven). At least three fungal species were isolated in 14.4% of samples (17.9% of positive cultures), and at least two were isolated in 41.2% of samples (51.1% of positive cultures). Sterile mycelium was observed in 671 samples (42.28%), while Candida was identified in 607 samples (38.25%), and Geotrichum was identified in 271 samples (17.08%). Moulds were more frequently associated with bronchiectasis, while yeasts were associated with infectious pneumonia. Both moulds and yeasts were less frequent in diffuse interstitial lung disease, and yeast was less frequently present in chronic cough. Although overall, sterile mycelium and Candida were most frequently observed regardless of the underlying disease, there was nonetheless significant variability in the fungal genera between diseases. Fungal spores are highly prevalent in respiratory samples in Martinique. The species present in the samples varied according to the underlying respiratory disease.

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.

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.

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.