Intra-pocket ultrasound-guided axillary vein puncture vs. cephalic vein cutdown for cardiac electronic device implantation: the ACCESS trial.

BACKGROUND AND AIMS: Intra-pocket ultrasound-guided axillary vein puncture (IPUS-AVP) for venous access in implantation of transvenous cardiac implantable electronic devices (CIED) is uncommon due to the lack of clinical evidence supporting this technique. This study investigated the efficacy and early complications of IPUS-AVP compared to the standard method using cephalic vein cutdown (CVC) for CIED implantation. METHODS: ACCESS was an investigator-led, interventional, randomized (1:1 ratio), monocentric, controlled superiority trial. A total of 200 patients undergoing CIED implantation were randomized to IPUS-AVP (n = 101) or CVC (n = 99) as a first assigned route. The primary endpoint was the success rate of insertion of all leads using the first assigned venous access technique. The secondary endpoints were time to venous access, total procedure duration, fluoroscopy time, X-ray exposure, and complications. Complications were monitored during a follow-up period of three months after procedure. RESULTS: IPUS-AVP was significantly superior to CVC for the primary endpoint with 100 (99.0%) vs. 86 (86.9%) procedural successes (P = .001). Cephalic vein cutdown followed by subclavian vein puncture was successful in a total of 95 (96.0%) patients, P = .21 vs. IPUS-AVP. All secondary endpoints were also significantly improved in the IPUS-AVP group with reduction in time to venous access [3.4 vs. 10.6 min, geometric mean ratio (GMR) 0.32 (95% confidence interval, CI, 0.28-0.36), P < .001], total procedure duration [33.8 vs. 46.9 min, GMR 0.72 (95% CI 0.67-0.78), P < .001], fluoroscopy time [2.4 vs. 3.3 min, GMR 0.74 (95% CI 0.63-0.86), P < .001], and X-ray exposure [1083 vs. 1423 mGy.cm², GMR 0.76 (95% CI 0.62-0.93), P = .009]. There was no significant difference in complication rates between groups (P = .68). CONCLUSIONS: IPUS-AVP is superior to CVC in terms of success rate, time to venous access, procedure duration, and radiation exposure. Complication rates were similar between the two groups. Intra-pocket ultrasound-guided axillary vein puncture should be a recommended venous access technique for CIED implantation.

Cardiac Effects of BRAF and MEK Inhibitors: Mechanisms and Clinical Management.

PURPOSE OF REVIEW: The identification of BRAF mutation prompted the development of new class of targeted therapy for treating melanoma: BRAF inhibitors and MEK inhibitors. Cardiovascular events have been reported with these treatments and could counterbalance their long-term maintenance. RECENT FINDINGS: LVEF decrease due to BRAF and MEK inhibitors appears fairly common (10%) but usually not severe, without impact on patient outcomes. To date, no treatment options have been tested to prevent or to treat a decrease of LVEF associated with BRAF and MEK inhibitors. QTc prolongation was observed in 3% and arterial hypertension in 20% during treatment but only one-third of cases required a therapeutic change. BRAF and MEK inhibitors have revolutionized the management and the prognosis of melanoma patients. Cardio-oncology units may be useful for a better care of potential cardiac toxicity and particularly to inappropriately avoid discontinuing BRAF and MEK inhibitors.

Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study.

BACKGROUND: Gitelman syndrome is a salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. Previous studies suggested an intermediate phenotype for heterozygous carriers. METHODS: To evaluate the phenotype of heterozygous carriers of pathogenic SLC12A3 mutations, we performed a cross-sectional study of patients with Gitelman syndrome, heterozygous carriers, and healthy noncarriers. Participants measured their BP at home for three consecutive days before hospital admission for blood and urine sampling and an oral glucose tolerance test. RESULTS: We enrolled 242 participants, aged 18-75 years, including 81 heterozygous carriers, 82 healthy noncarriers, and 79 patients with Gitelman syndrome. The three groups had similar age, sex ratio, and body mass index. Compared with healthy noncarriers, heterozygous carriers showed significantly higher serum calcium concentration (P=0.01) and a trend for higher plasma aldosterone (P=0.06), but measures of home BP, plasma and urine electrolytes, renin, parathyroid hormone, vitamin D, and response to oral glucose tolerance testing were similar. Patients with Gitelman syndrome had lower systolic BP and higher heart rate than noncarriers and heterozygote carriers; they also had significantly higher fasting serum glucose concentration, higher levels of markers of insulin resistance, and a three-fold higher sensitivity to overweight. According to oral glucose tolerance testing, approximately 14% of patients with Gitelman syndrome were prediabetic, compared with 5% of heterozygous carriers and 4% of healthy noncarriers. CONCLUSIONS: Heterozygous carriers had a weak intermediate phenotype, between that of healthy noncarriers and patients with Gitelman syndrome. Moreover, the latter are at risk for development of type 2 diabetes, indicating the heightened importance of body weight control in these patients.

MRI-based detection of renal artery abnormalities related to renal denervation by catheter-based radiofrequency ablation in drug resistant hypertensive patients.

OBJECTIVES: Endovascular renal denervation (RDN) using catheter-based radiofrequency (RF) ablation has emerged as a potential treatment option for drug-resistant hypertension. Its efficacy is currently under debate. We aimed to evaluate the capability of contrast-enhanced magnetic resonance imaging (MRI) to assess the effects of RDN on the renal arterial wall in patients presenting with drug-resistant hypertension. METHODS: Patients were included prospectively following institutional review board approval and written informed consent. Renal arteries were imaged using a two-dimensional T1-weighted TSE sequence pre- and post-administration of a gadolinium-based contrast agent, before (D0), 2 days (D2) and 6 months (M6) after RDN. Mean enhancement of the wall (mENH) and mean wall thickness (mWT) were compared across time using an ANOVA with repeated measures and post-hoc paired t-test. RESULTS: Follow-up was completed for 23 patients (median age, 57 years; 16 men). The mENH at D2 (96.3 ± 36.0 %) was significantly higher than at D0 (61.1 ± 26.3%, p < 0.001) and M6 (66.1±22.7%, p < 0.001). Similarly, mWT was significantly higher at D2 (3.1 ± 0.4 m) than at D0 (2.7 ± 0.4mm, p < 0.001) and M6 (2.9 ± 0. 5 mm, p = 0.002). CONCLUSIONS: MRI demonstrated abnormalities of the arterial wall 2 days after RDN that had resolved at 6 months. KEY POINTS: • Contrast-enhanced MRI provides anatomic evidence of renal artery RF ablation • Temperature increase related to RF ablation induces transient arterial wall inflammation • Morphological effects observed 2 days post RF ablation are not visible after 6 months.

Clinical and Genetic Spectrum of Bartter Syndrome Type 3.

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

BACKGROUND: The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. METHODS: One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. RESULTS: The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. CONCLUSIONS: In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. METHODS: The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. FINDINGS: Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. INTERPRETATION: In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. FUNDING: French Ministry of Health.

Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension.

Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.

[Renal artery stenosis]. / Sténoses artérielles rénales.

Renal artery stenosis (RAS) is found in 1 to 2% of all hypertensive patients. Its diagnosis involves as a first step Doppler ultrasound and as a confirmatory test, CT scan or MRI. When the diagnosis isconfirmed, three questions should be addressed by the clinician: 1) the anatomical orm that is, fibromuscular dysplasia (FD) or atherosclerotic RAS (ARAS); 2) the potential relation between RAS and hypertension with major differences according to the two main etiologies; in the presence of FD hypertension is a priorir elated to the stenosis while it is not the case with ARAS; 3) is there an indication for revascularization with again two opposite situations. Renal angioplasty may cure up to one third of patients with FD and improve blood pressure control in some others and has thus to be discussed in this clinical context. On the contrary, several randomized trials have shown that the blood pressure benefit of renal revascularization is limited if any in ARAS and, above all, not associated with an improvement of cardiovascular and renal outcomes. Renal angioplasty should thus be restricted to highly selected patients while in all cases, cardiovascular prevention should be intensified, based on renin angiotensin system blockers, statins, and aspirin use. Whatever the management, these patients should be followed both on the renal side to detect restenosis or renal impairment, and on other cardiovascular complications particularly in the presence of ARAS.

Physics-Guided Neural Networks for Intraventricular Vector Flow Mapping.

Intraventricular vector flow mapping (iVFM) seeks to enhance and quantify color Doppler in cardiac imaging. In this study, we propose novel alternatives to the traditional iVFM optimization scheme by utilizing physics-informed neural networks (PINNs) and a physics-guided nnU-Net-based supervised approach. When evaluated on simulated color Doppler images derived from a patient-specific computational fluid dynamics model and in vivo Doppler acquisitions, both approaches demonstrate comparable reconstruction performance to the original iVFM algorithm. The efficiency of PINNs is boosted through dual-stage optimization and pre-optimized weights. On the other hand, the nnU-Net method excels in generalizability and real-time capabilities. Notably, nnU-Net shows superior robustness on sparse and truncated Doppler data while maintaining independence from explicit boundary conditions. Overall, our results highlight the effectiveness of these methods in reconstructing intraventricular vector blood flow. The study also suggests potential applications of PINNs in ultrafast color Doppler imaging and the incorporation of fluid dynamics equations to derive biomarkers for cardiovascular diseases based on blood flow.

Association Between Aortic Wall Thrombus and Thromboembolic Events After Transfemoral Transcatheter Aortic Valve Replacement.

BACKGROUND: Thromboembolic events, particularly strokes, remain a major complication of transcatheter aortic valve replacement (TAVR). Embolic protection devices have failed to show significant clinical benefit in large randomized clinical trials. Aortic wall thrombus (AWT) is often observed on multidetector computed tomography during TAVR work-up, but its prognostic significance is uncertain. OBJECTIVES: This study sought to evaluate the association between the presence of AWT and the incidence of thromboembolic outcomes in patients undergoing transfemoral (TF) TAVR for severe aortic stenosis. METHODS: This was a prospective cohort study of consecutive patients who underwent TF TAVR for severe aortic stenosis between January 2011 and April 2022. A dedicated scale (range: 0-10) was qualitatively used to assess AWT. The primary outcome was a composite of procedural thromboembolic events defined as ischemic stroke, blue toe syndrome, bowel ischemia, or other solid organ infarction. The secondary endpoints were ischemic strokes and procedural death. RESULTS: Of the 641 patients included, severe AWT (score ≥8) was identified in 73 (11.4%). The presence of severe AWT was strongly associated with an increase in the primary outcome (OR: 8.48; 95% CI: 3.36-21.40; P < 0.001). This relationship persisted following multivariable analysis, which adjusted for comorbidities and procedural characteristics. The presence of severe AWT was also found to be associated with an increased incidence of stroke and procedural death (OR: 5.66; 95% CI: 2.00-15.30; P = 0.002 and OR: 4.66; 95% CI: 1.80-11.30; P = 0.002, respectively). CONCLUSIONS: The presence of severe AWT on preprocedural multidetector computed tomography is strongly associated with thromboembolic complications including stroke and mortality after TF TAVR.

Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.

Focus on echocardiographic and Doppler analysis of coronary artery abnormal origin from the pulmonary trunk with mild myocardial dysfunction.

BACKGROUND: Late presentation of abnormal origin of coronary artery from the pulmonary artery (ACAPA) is uncommon compared with early presentation, which usually induces extended myocardial necrosis and severe heart failure. The late presentation is characterized by abundant development of intercoronary collaterals resulting in mild and rare symptoms, but nevertheless can cause sudden cardiac death. Our objective was to describe presentation, cardiovascular imaging methods for diagnosis and outcomes of patients with late presentation of ACAP. METHODS: The study is a retrospective review of a single-center database to identify all patients diagnosed with ACAPA beyond the first year of life. RESULTS: From 1976 to 2011, 10 patients were identified with ACAPA at the age of 1.1-64 years: 6 with left coronary artery from the pulmonary artery (ALCAPA) and 4 with right coronary artery from the pulmonary artery (ARCAPA). Echocardiography and Doppler imaging evidenced: (1) direct signs: the abnormal coronary ostium arising from the pulmonary trunk with retrograde coronary artery flow and (2) indirect signs: abundant intercoronary septal collaterals with anterograde flow (ARCAPA) or retrograde flow (ALCAPA) and dilatation of the controlateral normally originated coronary artery. Nine patients underwent surgical implantation of the ACAPA into the ascending aorta. After 7.9 years mean follow-up, all were asymptomatic except one who required a second surgery. CONCLUSIONS: Noninvasive cardiovascular imaging, namely transthoracic echocardiography and Doppler specific parameters, can reach diagnosis of late presentation of ACAPA. Direct aortic implantation is a reliable and effective to establish dual coronary artery circulation and prevent risks due to myocardial ischemia.

Sequencing and titrating approach of therapy in heart failure with reduced ejection fraction following the 2021 European Society of Cardiology guidelines: an international cardiology survey.

AIMS: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. METHODS AND RESULTS: An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. CONCLUSION: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices.

Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis.

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.

Churg-Strauss syndrome presenting with acute myocarditis and cardiogenic shock.

Churg-Strauss syndrome (CSS) is a multisystem disorder characterised by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. We report the case of a 22 year-old man admitted to the intensive care unit for acute myocarditis complicated with cardiogenic shock. Eosinophilia, history of asthma, lung infiltrates, paranasal sinusitis, glomerulonephritis, and abdominal pain suggested the diagnosis of CSS. Cardiac MRI confirmed cardiac involvement with a diffuse subendocardial delayed enhancement of the left ventricular wall, and a left ventricular ejection fraction (LVEF) of 30%. Acute myocarditis was confirmed with myocardial biopsy. The patient was successfully treated with systemic corticosteroids, intravenous cyclophosphamide, vasopressor inotropes, intra-aortic balloon pump and mechanical ventilation, and was discharged 21 days later. One year after diagnosis, the patient was asymptomatic. The eosinophilic cell count was normal. Follow-up MRI at one year showed LVEF of 40% with persistent delayed enhancement. Cardiac involvement by CSS requires immediate therapy with corticosteroids and cyclophosphamide, which may allow recovery of the cardiac function.

Screening for hypertension-mediated organ damage and aetiology: still of value after 65 years of age?

BACKGROUND: Secondary forms and hypertension-mediated organ damage (HMOD) may differ between younger and older hypertensive patients. The aim of the present study was to explore the specificity of HMOD and secondary forms in patients ≥ 65 years in comparison to younger ones in a contemporary cohort. METHODS: We analysed 938 patients recruited between 2004 and 2014 (Cardiology department, Croix-Rousse Hospital, Lyon) who had at baseline HMOD and secondary forms screening among them 190 were ≥ 65 years. RESULTS: The mean (2.1 ± 0.8 vs. 1.2 ± 0.9, P < 0.001) and frequency of HMOD (96.3% vs. 72.9%, P < 0.001) was higher in patients ≥ 65 years than younger ones. Carotid femoral pulse wave velocity > 10 m/s was the most frequent HMOD in patients ≥ 65 years (90.1%), while echocardiographic left ventricular hypertrophy was the most common in the younger patients (45.0%). Among ECG left ventricular indexes, only R wave in aVL lead was significantly more frequently observed in patients ≥ 65 years (32.6%) than in younger ones (19.0%, P < 0.001). The frequency of secondary hypertension was not significantly different between younger and older patients (respectively; 30.5% vs. 27.8%, P = 0.487). The most frequent aetiology was primary aldosteronism regardless of age, followed by renovascular hypertension (6.3% vs. 3.3%, P = 0.038). Among older patients, 3.2% were treated with adrenalectomy and 6.3% with percutaneous transluminal renal angioplasty. CONCLUSION: Extensive screening of HMOD in older patients may be questionable as nearly all patients had one; aetiology must however be explored as a third of older patients had a secondary form.