Right Ventriculoarterial Coupling Surrogates and Long-Term Survival in LVAD Recipients: Results of the ASSIST-ICD Multicentric Registry.

BACKGROUND: Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. METHODS: The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. RESULTS: The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). CONCLUSION: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

Performance of Mucorales spp. qPCR in bronchoalveolar lavage fluid for the diagnosis of pulmonary mucormycosis.

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.

Prospective cardiovascular events in patients with advanced thoracic cancer treated with immune checkpoint inhibitor.

INTRODUCTION: Myocarditis is the most lethal cardiovascular immune related adverse events with a low incidence, depending on the studies. We prospectively studied the potential interest of a systematic screening to early detect immune related myocarditis and confirm the incidence of immune-induced myocarditis in advanced lung cancer and the impact of troponin systematic screening in early detection of other major cardiovascular events (MACE). MATERIAL AND METHODS: This prospective bicentric study includes adults who received at least one dose of immune checkpoint inhibitor (ICI) for advanced lung cancer. Cardiac biomarkers dosage, ECG and transthoracic echography (TTE) were done at baseline. Diagnosis of myocarditis was based on European Society of Cardiology recommendations. MACEs were reported during the observation period. RESULTS: Among 298 patients, 5 (1.68 %) immune-induced myocarditis occurred, all being asymptomatic with at first troponin elevation, treated by corticosteroids and ICI's discontinuation. No attributable death occurred, and no specific clinical characteristics were identified with myocarditis onset. Three patients were rechallenged with ICI after troponin normalization in the absence of other therapeutic options. Recurrence occurred in 2 patients, with a re-increase of troponin and a de novo modification of the ECG. Systematic cardiovascular screening also led to 14 cardiovascular diseases detection and 11 MACEs during ICI. CONCLUSION: Systematic cardiovascular screening has uncovered slightly more immuno-induced myocarditis cases than reported previously, but without altering treatment strategies due to their subclinical nature. Additionally, it helps detecting other cardiovascular diseases in this comorbid population.

Safety of immune checkpoint inhibitor rechallenge after severe immune-related adverse events: a retrospective analysis.

Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation 1. While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce 1,2. We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021. Fifteen patients were included, with a median time to severe irAE onset of 49 days. Among them, five patients experienced neurological adverse events (NAEs): aseptic meningitis (3), inflammatory polyradiculoneuropathy (1), and ophthalmoplegia (1), while one patient presented with myocarditis. Of the 15 patients retreated with ICIs after initial severe irAEs, 11 (73%) remained free of subsequent irAEs, two (13%) experienced recurrence of the initial irAE, and two (13%) developed new irAEs distinct from the initial event. The median time to event recurrence was 69 days, occurring no earlier than the initial severe irAE. In the subset analysis focusing on severe cardiovascular and neurological irAEs, rechallenge with ICIs was generally well tolerated. However, one patient treated with anti-PD1 experienced a relapse of grade 2 aseptic meningitis. Overall, our findings suggest that rechallenging with ICIs after severe irAEs, including those affecting the cardiovascular and neurological systems, may be safe, particularly after irAE regression and corticosteroid withdrawal.

Volumetric and Simultaneous Photoacoustic and Ultrasound Imaging With a Conventional Linear Array in a Multiview Scanning Scheme.

Volumetric, multimodal imaging with precise spatial and temporal coregistration can provide valuable and complementary information for diagnosis and monitoring. Considerable research has sought to combine 3-D photoacoustic (PA) and ultrasound (US) imaging in clinically translatable configurations; however, technical compromises currently result in poor image quality either for PA or ultrasonic modes. This work aims to provide translatable, high-quality, simultaneously coregistered dual-mode PA/US 3-D tomography. Volumetric imaging based on a synthetic aperture approach was implemented by interlacing PA and US acquisitions during a rotate-translate scan with a 5-MHz linear array (12 angles and 30-mm translation to image a 21-mm diameter, 19 mm long cylindrical volume within 21 s). For coregistration, an original calibration method using a specifically designed thread phantom was developed to estimate six geometrical parameters and one temporal offset through global optimization of the reconstructed sharpness and superposition of calibration phantom structures. Phantom design and cost function metrics were selected based on analysis of a numerical phantom and resulted in a high estimation accuracy for the seven parameters. Experimental estimations validated the calibration repeatability. The estimated parameters were used for the bimodal reconstruction of additional phantoms with either identical or distinct spatial distributions of US and PA contrasts. The superposition distance of the two modes was within < 10% of the acoustic wavelength, and a wavelength-order uniform spatial resolution was obtained. This dual-mode PA/US tomography should contribute to more sensitive and robust detection and follow-up of biological changes or the monitoring of slower-kinetic phenomena in living systems such as the accumulation of nanoagents.

Multidisciplinary cardiogenic shock team approach improves the long-term outcomes of patients suffering from refractory cardiogenic shock treated with short-term mechanical circulatory support.

AIMS: Short-term mechanical circulatory support (STMCS) may be used as an intentional escalation strategy to treat refractory cardiogenic shock (rCS). However, with growing technical possibilities, making the right choice at the right time can be challenging. We established a shock team in January 2013 comprising a cardiac anaesthetist-intensivist, an interventional cardiologist, and a cardiac surgeon. Since then, a diagnosis of rCS has triggered a multidisciplinary team meeting based on a common algorithm. This study aimed to compare the decision-making process for STMCS for rCS before (2007-2013) and after (2013-2019) the creation of the shock team. METHODS AND RESULTS: This before-and-after cohort study was conducted over a 156-month period. Post-cardiotomy rCS were excluded. The primary outcome was a 1-year survival rate. In total, 250 consecutive adult patients were included in the analysis (84 in the control group and 166 in the shock team group). At baseline, the CardShock score was not different between the two groups (5[3-5] vs. 5[4-6], P = 0.323). The 1-year survival rate was significantly higher in the shock team group compared with the control group (59% vs. 45%, P = 0.043). After a Cox regression analysis, the shock team intervention was independently associated with a significantly improved 1-year survival rate (HR: 0.592, 95% CI: 0.398-0.880, P = 0.010). CONCLUSION: A multidisciplinary shock team-based decision for STMCS device implantation in rCS is associated with better 1-year survival rates.

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series.

BACKGROUND: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening. METHODS: We conducted a multicenter cross-sectional retrospective study with the aim of better characterizing ICI-related myocarditis. Myocarditis diagnosis was based on the recent consensus statement of the International Cardio-Oncology Society. RESULTS: Twenty-nine patients were identified, from six different referral centers. Most patients (55%) were treated using anti-programmed-death 1, rather than ICI combination (35%) or anti-programmed-death-ligand 1 (10%). Transthoracic echocardiography was abnormal in 52% of them, and cardiac magnetic resonance showed abnormal features in 14/24 patients (58%). Eleven patients (38%) were classified as severe. Compared with other patients, they had more frequently pre-existing systemic autoimmune disease (45% vs 6%, p=0.018), higher troponin level on admission (42-fold the upper limit vs 3.55-fold, p=0.001), and exhibited anti-acetylcholine receptor autoantibodies (p=0.001). Seven patients (24%) had myocarditis-related death, and eight more patients died from cancer progression during follow-up. Twenty-eight patients received glucocorticoids, 10 underwent plasma exchanges, 8 received intravenous immunoglobulins, and 5 other immunosuppressants. ICI rechallenge was performed in six patients, with only one myocarditis relapse. DISCUSSION: The management of ICI-related myocarditis may be challenging and requires a multidisciplinary approach. Prognostic features are herein described and may help to allow ICI rechallenge for some patients with smoldering presentation, after an accurate evaluation of benefit-risk balance.

A Prospective Study to Detect Immune Checkpoint Inhibitors Associated With Myocarditis Among Patients Treated for Lung Cancer.

Background: Immune checkpoint inhibitors (ICIs) are widely used in lung cancer management. However, myocarditis, which is a rare, yet potentially severe adverse-related event associated with ICIs, could be under-reported. Objectives: This study is aimed to prospectively evaluate the cumulative incidence rate of myocarditis, through systematic screening, among patients receiving ICIs for lung cancer. Methods: All patients who received the first administration of ICIs for non-small cell (NSCLC) and small cell lung cancer (SCLC), between May and November 2020, in the pulmonary department of Bordeaux University Hospital, were included. Echocardiography (ECG), troponin-I, and natriuretic peptide dosages before ICIs' first administration and before each infusion were recorded. ECG and magnetic resonance imaging (MRI) were done additionally, in case of at least three times increase in troponin levels, ECG modifications, and the onset of cardiovascular symptoms. Second, if possible, coronarography than endomyocardial biopsy was assessed. The primary outcome was defined as ICIs related to myocarditis onset, while secondary outcomes included other cardiovascular events, disease-free, and overall survival. Results: During the period of interest, 99 patients received their first infusion of ICIs for lung cancer (mean age 64 ± 9 years; 52 men, 67% with adenocarcinoma). Three cases of myocarditis without major adverse cardiac events (MACEs) occurred (two definite and one possible), and the mean duration between the first ICIs' administration and myocarditis onset was 144 ± 3 days. Median disease-free survival and overall survival were 169 [102; 233] days and 209 [147; 249] days, respectively. Conclusion: In our study, systematic screening of myocarditis associated with ICIs leads to a more frequent incidence and a later onset than previously reported. None of them were severe. Additional prospective evidence is needed before we could adopt routine cardiac screening in unselected patients starting ICIs; however, these data shed new light on the risk of myocarditis associated with ICIs administration.

Clinical profile and midterm prognosis of left ventricular thrombus in heart failure.

AIMS: We documented the midterm prognosis of left ventricular thrombus (LVT) in heart failure (HF) patients with dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). We aimed to characterize patients with LVT in the context of HF with reduced (≤40%) left ventricular ejection fraction and evaluate their risk for death and/or embolic events, overall, and specifically in patients with ischaemic or non-ischaemic aetiology. We also intended to identify risk factors for LVT in patients with DCM. METHODS AND RESULTS: We included all HF patients (N = 105, age 56 ± 13) admitted from 2005 to 2018 in our institution for LVT without significant valve disease/prosthesis, heart transplant/left ventricular assist device, congenital heart disease, or acute myocardial infarction. Our primary endpoint was the 1 year risk of the composite of all-cause mortality (ACM) and symptomatic embolic events. Mean left ventricular ejection fraction was 23 ± 9%, and median BNP was 1795 pg/mL. Most (97%) patients were treated with vitamin K anticoagulants, and 64% had ICM. Symptomatic embolic events and/or ACM occurred in 20% of the population [embolic events (all within 30 days of LVT diagnosis) 15% and ACM 6%] and was similarly frequent in DCM or ICM (P > 0.05). Suspected/transient embolic events were more frequent in DCM (overall 13%; 29% in DCM vs. 5% in ICM, P < 0.01). Major bleeding occurred in 5% of patients. Left ventricular reverse remodelling occurred in 65% of patients, more frequently in DCM (86% in DCM vs. 65% in ICM, P = 0.02). In a case-control analysis matching DCM patients, BNP level was the only factor significantly associated with LVT (2447 pg/mL in LVT vs. 347 pg/mL, P < 0.001). CONCLUSIONS: Patients with LVT have markedly high natriuretic peptides and experience a 20% 1 year risk for embolic events and/or death following diagnosis despite anticoagulant treatment. Most patients have favourable remodelling/recovery. As all symptomatic embolic events occurred within 30 days of LVT diagnosis, a very careful initial management is warranted.