Left atrial strain analysis and new-onset atrial fibrillation in patients with ST-segment elevation myocardial infarction: A prospective echocardiography study.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a well-known complication of ST-segment elevation myocardial infarction (STEMI), probably due to left atrial (LA) remodelling. LA strain (LAS) can predict NOAF in several cardiovascular diseases. OBJECTIVE: To assess whether LAS predicts NOAF in sinus rhythm patients with STEMI during hospitalization. METHODS: Adults with a STEMI and transthoracic echocardiography performed within 48hours of admission were included. LAS analysis, performed by automated software, recorded LAS during the reservoir phase (LASr), the conduit phase (LAScd) and the contraction phase (LASct). RESULTS: From May 2021 to November 2022, 175 patients were included, 21 (12%) of whom developed NOAF. NOAF patients were older (median [Q1-Q3]: 67 [59-80] vs 59 [51-67]years; P=0.006) and had a higher Thrombolysis In Myocardial Infarction scores (4 [2-7] vs 3 [1-4]; P=0.005). All LAS parameters were significantly impaired in NOAF patients, especially LASr (13.0% [10.5-28.4] vs 36.6% [29.0-44.9]; P=0.001). An LASr cut-off of 27% had a sensitivity of 81% and a specificity of 80% to identify patients with NOAF. In a multivariable model, LASr was significantly associated with NOAF (odds ratio 1.18, 95% confidence interval 1.09-1.26; P=0.003). The cumulative risk of NOAF during hospital stay was 30% (18-43 with LASr<27% and 4% [1.5-8.5] with LASr≥27% [P<0.0001]). CONCLUSION: NOAF is a frequent complication of STEMI. LASr seems helpful for identifying patients at high risk of NOAF during hospitalization.

In-hospital prognosis of acute ST-elevation myocardial infarction in patients with recent recreational drug use.

AIMS: Although recreational drug use may induce ST-elevated myocardial infarction (STEMI), its prevalence in patients hospitalized in intensive cardiac care units (ICCUs), as well as its short-term cardiovascular consequences, remains unknown. We aimed to assess the in-hospital prognosis of STEMI in patients with recreational drug use from the ADDICT-ICCU study. METHODS AND RESULTS: From 7-22 April 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-methylenedioxymethamphetamine: 0.6%). The prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, P < 0.001), and more active smokers (78% vs. 34%, P < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). Major adverse cardiac events (17.1% vs. 3.5%, P < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, P = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (odds ratio = 13.1; 95% confidence interval: 3.4-54.6). CONCLUSION: In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia. TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT05063097.

Prognostic Value of Right Ventricular Longitudinal Shortening Fraction in Patients With ST-Elevation Myocardial Infarction: A Prospective Echocardiography Study.

Right ventricular systolic dysfunction (RVsD) frequently occurs in patients with ST-elevation myocardial infarction (STEMI). However, the diagnosis depends on the echocardiographic parameters to define RVsD. The right ventricle longitudinal shortening fraction (RV-LSF) is an accurate and reproducible 2-dimensional speckle-tracking parameter associated with clinical events in various pathologies. This study aimed to evaluate the association between RVsD and major adverse cardiovascular event (MACE) occurrence in a cohort of patients with STEMI. Adult patients with STEMI admitted to Amiens University Hospital's cardiovascular intensive care unit between May 2021 and November 2022 who underwent coronary angiography and transthoracic echocardiography within 48 hours of admission were included. RVsD was defined as RV-LSF <20%. The primary outcome was MACE occurrence, including heart failure, myocardial infarction, stroke, and death within 6 months of admission. A multivariable Cox regression analysis with proportional hazard ratio models assessed the association between RVsD and MACEs. In the 164 included patients, 72 (44%) had RVsD and 92 (56%) did not. The RVsD group had a significantly higher proportion of MACEs during the 6-month follow-up (n = 23 of 72, 33%) than the group without RVsD (n = 8 of 92, 9%, p = 0.001). RVsD showed an independent association with MACEs at 6 months (hazard ratio 3.1, 95% confidence interval [CI] 1.35 to 7.30, p = 0.008). Left ventricular ejection fraction <40% and Thrombolysis in Myocardial Infarction score >4 were independently associated with RVsD (odds ratio 2.80, 95% CI 1.34 to 5.98 and odds ratio 2.15, 95% CI 1.18 to 4.39, respectively, p = 0.015). The cumulative risk of MACEs at 6 months was 33% for RV-LSF <20% and 9% for RV-LSF ≥20% (log-rank test p <0.001). RVsD, defined by RV-LSF <20%, is associated with an increased risk of MACEs after STEMI.

Improvement of the Prognosis Assessment of Severe Tricuspid Regurgitation by the Use of a Five-Grade Classification of Severity.

It is well known that some patients present with "more than severe" tricuspid regurgitation (TR). We aimed to assess the prognosis of these very severe TR patients. We defined very severe TR using 3 simple echocardiographic parameters: a coaptation gap≥10mm, a laminar TR flow and a systolic reversal of the hepatic vein flow. We included 259 consecutive patients (76 ± 13 years; 46% men) with moderate-to-severe TR (n = 114) and severe TR (n = 145). The primary end point was the combination of hospitalisation for right heart failure (RHF) and cardiovascular mortality. Median follow-up was 24(7 to 47) months. In patients with severe TR, 52 (36%) met the definition of very severe TR. These patients were younger, had more history of RHF and were more frequently treated with loop diuretics than those with moderate-to-severe TR (all p < 0.001). Four-year event-free survival rates were 68 ± 5%, for moderate-to-severe TR, 48 ± 6% for severe TR and only 35 ± 7% for very-severe TR (p < 0.001). On multivariable analysis, after adjustment for outcome predictors including age, comorbidity, RHF, TR etiology, left and right ventricular dysfunction, and tricuspid valve surgery, patients with very severe TR had a worsened prognosis than those with moderate-to-severe TR (Adjusted Hazard Ratio [95% Confidence Interval] = 2.43 [1.18 to 5.53]; p = 0.002) and than those with severe TR (Adjusted Hazard Ratio [95% Confidence Interval] = 2.23 [1.06 to 5.56]; p = 0.015). In conclusion, very severe TR is frequent in patients with severe TR, corresponds to a more advanced stage of the disease and is associated with poor outcomes. Therefore, the use of a 5-grade classification of TR severity is justified in routine clinical practice. (ID-RCB: 2017-A03233-50).

Characteristics and prognosis of patients with significant tricuspid regurgitation.

BACKGROUND: Severe tricuspid regurgitation (TR) usually remains asymptomatic for a long period, and the diagnosis is often delayed until an advanced stage of right heart failure (RHF). Only a minority of patients are referred for surgery. AIM: To describe the characteristics and prognosis of patients with significant TR, according to aetiology. METHOD: Two-hundred and eight consecutive patients with moderate-to-severe (grade III) or severe (grade IV) TR were included from echocardiography reports between 2013 and 2017. Median follow-up was 18 (6-38) months. RESULTS: Patients (mean age 75 years; 46.6% men) were divided into four groups according to TR aetiology: group 1, primary TR (14.9%); group 2, TR secondary to left heart disease with a history of left heart valve surgery (24.5%); group 3, TR secondary to left heart or pulmonary disease with no history of left valvular surgery (26.5%); and group 4, idiopathic TR (34.1%). During follow-up, 61 patients (29.3%) experienced at least one episode of RHF decompensation requiring hospitalization. Only 11 patients (5.3%) underwent tricuspid valve surgery during follow-up. The 4-year survival was much lower than the expected survival of age- and sex-matched individuals in the general population (56±4% vs. 74%). After adjustment for outcome predictors, patients with idiopathic TR had a higher risk of mortality (adjusted hazard ratio 1.83, 95% confidence interval 1.05-3.21; P=0.034) compared with other groups. CONCLUSIONS: Moderate-to-severe or severe TR is associated with a high risk of hospitalization for RHF and death at 4 years, and a low rate of surgery. Idiopathic TR is associated with worse outcome than other aetiologies.

A six-gene signature predicting breast cancer lung metastasis.

The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasis-associated genes. Using a cohort of 72 lymph node-negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model.

Gene arrays for diagnosis, prognosis and treatment of breast cancer metastasis.

The advent of microarray tools has generated a massive amount of gene expression data. These data have greatly enhanced our understanding of the biology of breast cancer metastasis and provide a way to improve the prediction of the metastatic potential of breast tumours. Gene-expression profiling has highlighted the molecular heterogeneity of mammary tumours and contributed to the identification of a new molecular classification of breast cancers. In addition, several molecular signatures predicting the likelihood of distant metastases for breast cancer patients have been characterized. Further reports have described gene expression profiles associated with specific metastatic phenotypes, including the organ preference of breast cancer metastasis. Here we review the major studies that had important impacts on the understanding of breast cancer metastasis. We also discuss the future challenges in this research field and the special issues that still need to be examined.

Functional pathways shared by liver and lung metastases: a mitochondrial chaperone machine is up-regulated in soft-tissue breast cancer metastasis.

Genes that mediate breast cancer metastasis to lung are different from those which mediate bone metastasis. However, which markers accounts for the diversity of breast cancer metastasis remains unknown. The aim of this study was identify proteins associated with the soft-tissue metastatic ability of breast cancer tumors in metastases, coupling microarray data from clinical metastases and immunohistochemistry, for further screening for early detection at the first diagnosis in patients. We use a bioinformatic program to create and analyze protein interaction networks from protein experimental data, and to translate RNA expression analysis of breast cancer human metastases to protein, in a search for the phenotype associated with soft-tissue metastases. The pre-validated proteins constituted the protein signature for each metastasis: 37 (8.9%) from liver, 92 (8.5%) from lung and 167 (13%) from bone. Pleiotrophin, BAG 2, HSP 60 and vinculin were pre-validated in liver and lung metastases performing the soft-tissue phenotype. After IHC validation, we conclude that HSP 60, one of the best-known mitochondrial chaperone machines, is a key protein in soft-tissue metastases phenotype interacting with BAG 2, which competes for binding to GRP 75, the other mitochondrial chaperone. The relationship between HSP 60/GRP 75 and BAG 2 might result in the activation of several transcription pathways, different in liver from in lung metastases, as a nodal point coupling positive and negative actuators in the multiple survival-signal pathways and so achieving metastatic growth.