Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a Phase 2 study of patients with chronic HCV infection.

BACKGROUND & AIMS: TG4040 is a modified vaccinia Ankara (MVA) virus that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase II open-label study to determine the efficacy, safety, and immunotherapeutic properties of TG4040 in combination with pegylated interferon α-2a and ribavirin (PEG-IFNα/RBV) in patients with chronic HCV infection. METHODS: Treatment-naive patients with HCV genotype 1 infection were assigned randomly to 1 of the following groups: PEG-IFNα/RBV for 48 weeks (group A, n = 31), PEG-IFNα/RBV for 4 weeks followed by PEG-IFNα/RBV for 44 weeks with 6 injections of TG4040 (group B, n = 63), or TG4040 for 12 weeks (7 injections) followed by PEG-IFNα/RBV for 48 weeks with 6 injections of TG4040 (group C, n = 59). The primary end point was complete early virologic response (cEVR), defined as HCV-RNA level less than 10 IU/mL after 12 weeks of PEG-IFNα/RBV treatment. RESULTS: In group C, 64.2% of evaluable patients achieved cEVR, compared with 30.0% in group A and 45.9% in group B (P = .0003 for group C vs A). A higher percentage of patients achieved a sustained virologic response 24 weeks after therapy ended in group C (58.2%) than in groups A (48.4%) or B (50.8%). HCV- and MVA-specific T-cell responses were observed predominantly in group C. As expected, most patients given injections of TG4040 developed anti-MVA antibodies. The combination of TG4040 and PEG-IFNα/RBV was reasonably well tolerated. However, PEG-IFNα-associated thrombocytopenia developed in 3 patients who carried the class II HLA allele DRB01*04. CONCLUSIONS: A higher percentage of patients with chronic HCV infection who received immunotherapy with TG4040 followed by TG4040 and PEG-IFNα/RBV achieved a cEVR compared with patients who received only PEG-IFNα/RBV therapy. These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection. ClinicalTrials.gov number, NCT01055821.

Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients.

Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5% had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46%. The clinical response of the 37 targeted lesions led to an OOR of 51% and a DCR of 75%. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3-/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed.

Type 2 diabetes mellitus in acute myocardial infarction: a persistent significant burden on long-term mortality.

Objective: The long-term impact of type 2 diabetes mellitus (T2DM) after an acute myocardial infarction (AMI) has not been thoroughly investigated yet. This study aimed to assess the long-term impact of T2DM after AMI. Research design and methods: We analyzed the data of three nationwide observational studies from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting T2DM were classified as diabetic, and patients presenting type 1 diabetes mellitus were excluded. We identified factors related to all-cause death at 1-year follow-up and divided 1,897 subjects into two groups, paired based on their estimated 1-year probability of death as determined by a logistic regression model. Results: A total of 9,181 AMI patients were included in the analysis, among them 2,038 (22.2%) had T2DM. Patients with diabetes were significantly older (68.2 ± 12.0 vs. 63.8 ± 14.4, p < 0.001) and had a higher prevalence of a prior history of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or heart failure (22.5% vs. 13.0%, 7.1% vs. 3.1% and 6.7 vs. 3.8% respectively, p < 0.001 for all). Even after matching two groups of 1,897 patients based on propensity score for their 1-year probability of death, diabetes remained associated with long-term mortality, with an HR of 1.30, 95%CI (1.17-1.45), p < 0.001. Conclusions: T2DM per se has an adverse impact on long-term survival after myocardial infarction. Independently of the risk of short-term mortality, patients with diabetes who survived an AMI have a 30% higher risk of long-term mortality.

Association of Use and Dose of Lipid-Lowering Therapy Post Acute Myocardial Infarction With 5-Year Survival in Older Adults.

BACKGROUND: Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed. METHODS: The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences. RESULTS: Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66-0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80-1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62-0.98]). CONCLUSIONS: In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.

Sex disparities in cardiogenic shock: Insights from the FRENSHOCK registry.

BACKGROUND: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. OBJECTIVES: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS. METHODS: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. RESULTS: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. CONCLUSION: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038.

Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042.

BACKGROUND: Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL). METHODS: For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient's objective response at the end of the study. RESULTS: Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit. CONCLUSIONS: These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response. TRIAL REGISTRATION: The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693.

Outcomes of Provisional Stenting With Versus Without Side Branch Intervention in Patients With Bifurcation Lesion-Related ST-Segment Elevation Myocardial Infarction.

To date, the best approach to coronary bifurcation lesion remains unsettled, and the parameters to guide side branch ballooning or stenting are not yet defined. This study aimed to compare the survival outcomes after provisional stenting with versus without side branch intervention. A cohort was conducted on 132 patients who underwent coronary angiography at Toulouse University Hospital for ST-segment elevation myocardial infarction with large culprit nonleft main coronary bifurcation lesion. Study participants were divided into 2 groups depending on the performance or not of a side branch intervention. We observed the living status at 1-year after hospital discharge. Side branch intervention by balloon inflation or final balloon kissing technique was performed in 34.1% of study participants. At 1-year follow-up, the incidence of all-cause mortality was 7.8 per 100 person-years (95% confidence interval [CI] 4.1 to 15), and although it seemed higher in the side branch intervention group (10 per 100 person-years [95% CI 3.8 to 26.7] vs 6.6 per 100 persons-years [95% CI 2.8 to 15.9]), the survival analyses showed no differences in survival outcomes (hazard ratio side branch intervention 1.55 [0.42 to 5.78], p = 0.513). In conclusion, in the setting of a coronary bifurcation causing ST-segment elevation myocardial infarction, simple provisional stenting without side branch intervention showed a low mortality rate and no differences in the 1-year survival outcomes.

TIcagrelor in Rotational Atherectomy to Reduce TROPonin Enhancement: The TIRATROP Study, A Randomized Controlled Trial.

BACKGROUND: Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin release. METHODS: TIRATROP (TIcagrelor in Rotational Atherectomy to reduce TROPonin enhancement) is a multicenter double-blind randomized controlled trial that included 180 patients with severe calcified lesions requiring RA who received either clopidogrel (300 mg loading dose, then 75 mg/d) or ticagrelor (loading dose 180 mg then 90 mg twice daily). Blood samples were collected at the beginning (T0), and 6, 12, 18, 24 and 36 h after the procedure. Primary end point was troponin release within the first 24 h using area under the curve analysis (troponin level as a function of time). RESULTS: The mean age of patients was 76 ± 10 years, 35% had diabetes. RA was used to treat 1, 2 or 3 calcified lesions in 72%, 23% and 5% of patients, respectively. Troponin release within the first 24 h was similar in both the ticagrelor (adjusted mean ±SD of ln AUC 8.85 ± 0.33) and the clopidogrel (8.77 ± 0.34, p = 0.60) arms. Independent predictors for troponin enhancement were acute coronary syndrome presentation, renal failure, elevated C-Reactive protein and multiple lesions treated with RA. CONCLUSION: Troponin release did not differ among treatment arms. Our results suggest that greater platelet inhibition does not affect periprocedural myocardial necrosis in the setting of RA.

Very long-term outcomes after acute myocardial infarction in young men and women: Insights from the FAST-MI program.

AIMS: Conflicting data exists about long-term outcomes in young women and men experiencing acute myocardial infarction (AMI). METHODS: The FAST-MI program consists of three nationwide French surveys carried out 5years apart from 2005 to 2015, including consecutive patients with AMI over a 1-month period with up to 10-year follow-up. The present analysis focused on adults≤50 yo according to their gender. RESULTS: Women accounted for 17.5% (335) of the 1912 patients under 50 yo and had a similar age as men (43.9±5.1 vs. 43.9±5.5years, P=0.92). They received less percutaneous coronary interventions (PCI) than men (85.9% vs. 91.3%, P=0.005), even in ST-elevation myocardial infarction (83.6% vs. 93.5%, P<0.001). Recommended secondary prevention medications were less frequently prescribed at discharge in women (40.6% vs. 52.8%, P<0.001), a trend that persisted in 2015 (59.1% vs. 72.8% in 2015, P<0.001). Still, ten-year survival was similar in men (90.5%) and women (92.3%) (crude HR: 0.86 [95% CI: 0.55-1.35], P=0.52, adjusted HR: 0.63 [95% CI: 0.38-1.07], P=0.09); similar results were found for ten-year survival among hospital survivors (91.2% in men vs. 93.7% in women, adjusted HR: 0.87 [95% CI: 0.45-1.66], P=0.66). Of the 1684 patients alive at hospital discharge with morbidity follow-up≥6months available, death, AMI or stroke at 8years occurred in 12.9% men and 11.2% in women (adjusted HR: 0.90 [95% CI: 0.60-1.33], P=0.59). CONCLUSIONS: Young women with AMI undergo less cardiac interventions and are less often prescribed secondary prevention treatment than men, even when significant coronary artery disease is present, but keep a similar long-term prognosis after AMI. Optimal management of these young patients, regardless of gender, is necessary to ensure best outcomes after this major cardiovascular event.

Clinical Outcomes of Left Main Coronary Artery PCI With Rotational Atherectomy.

Data regarding rotational atherectomy percutaneous coronary intervention (RA PCI) angioplasty in the left main (LM) coronary artery are scarce, and mostly outdated. We aimed to describe clinical outcomes of RA PCI in LM. Patients requiring RA in 8 European countries and 19 centers were prospectively and consecutively included in the European registry of Cardiac Care of Calcified and Complex patients registry. In-hospital data collection and 1-year follow-up were performed for each patient. Between October 2016 and July 2018, 966 patients with complete data were included. Among them, 241 presented with an LM lesion, and 171 required an LM lesion preparation by RA. The latter, allocated to the LM-RA group, were compared with the 725 patients in the non-LM-RA group. Clinical success of the RA procedure was comparable in both groups, but in-hospital major adverse cardiac events were higher in the RA-LM group (7.6% vs 3.2%, adjusted p = 0.04), mainly driven by a higher in-hospital mortality rate (5.3 vs 0.3%, adjusted p = 0.005). At 1-year follow-up, mortality and major adverse cardiac event rates were comparable in both groups (12.9% vs 8.0%, adjusted p value: 0.821, and 15.8% vs 10.9%, adjusted p value: 0.329, respectively), but the rate of target vessel revascularization remained higher in the RA-LM group (5.3% vs 3.2%, adjusted p = 0.021). In conclusion, RA PCI is an efficient option for calcified LM lesions, providing acceptable outcomes regarding this population with high risk at 1 year, and yields comparable outcomes with RA PCI performed on non-LM lesions.

Health-Related Quality of Life and Its Association With Outcomes in Adults With Congenital Heart Disease and Heart Failure: Insight From FRESH-ACHD Registry.

Background Quality of Life (QoL) is a prognostic factor in heart failure (HF) of patients with acquired cardiac disease. The aim of this study was to determine the predictive value of QoL on outcomes in adults with congenital heart disease (ACHD) and HF. Methods and Results Quality of life of 196 adults with congenital heart disease with clinical heart failure (HF) (mean age: 44.3±13.8 years; 51% male; 56% with complex congenital heart disease; 47% New York Heart Association class III/IV) included in the prospective multicentric registry FRESH-ACHD (French Survey on Heart Failure-Adult with Congenital Heart Disease) was assessed using the 36-Item Short Form Survey (SF-36), a patient-reported survey. The primary end point was defined by all-cause death, HF-related hospitalization, heart transplantation, and mechanical circulatory support. At 12 months, 28 (14%) patients reached the combined end point. Patients with low quality of life experienced major adverse events more frequently (logrank P=0.013). On univariate analysis, lower score at physical functioning (hazard ratio [HR], 0.98 [95% CI, 0.97-0.99]; P=0.008), role limitations related to physical health (HR, 0.98 [95% CI, 0.97-0.99]; P=0.008), and general health dimensions of the SF-36 (HR, 0.97 [95% CI, 0.95-0.99]; P=0.002) were significantly predictive of cardiovascular events. However, after multivariable analysis, SF-36 dimensions were no longer significantly associated with the primary end point. Conclusions Patients with congenital heart disease with HF and poor quality of life experience severe events more frequently, making quality of life assessment and rehabilitation programs essential to alter their trajectory.

Mottling as a prognosis marker in cardiogenic shock.

AIMS: Impact of skin mottling has been poorly studied in patients admitted for cardiogenic shock. This study aimed to address this issue and identify determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies. METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October, 2016. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 660 had skin mottling assessed at admission (85.5%) with almost 39% of patients in cardiogenic shock presenting mottling. The need for invasive respiratory support was significantly higher in patients with mottling (50.2% vs. 30.1%, p < 0.001) and likewise for the need for renal replacement therapy (19.9% vs. 12.4%, p = 0.09). However, the need for mechanical circulatory support was similar in both groups. Patients with mottling at admission presented a higher length of stay (19 vs. 16 days, p = 0.033), a higher 30-day mortality rate (31% vs. 23.3%, p = 0.031), and also showed significantly higher mortality at 1-year (54% vs. 42%, p = 0.003). The subgroup of patients in whom mottling appeared during the first 24 h after admission had the worst prognosis at 30 days. CONCLUSION: Skin mottling at admission in patients with cardiogenic shock was statistically associated with prolonged length of stay and poor outcomes. As a perfusion-targeted resuscitation parameter, mottling is a simple, clinical-based approach and may thus help to improve and guide immediate goal-directed therapy to improve cardiogenic shock patients' outcomes.

Characteristics, management, and outcomes of active cancer patients with cardiogenic shock.

AIMS: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies. METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015]. CONCLUSION: Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer.

Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry.

BACKGROUND: Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles.

Five-year clinical outcomes using the bioresorbable vascular scaffold: Insights from the FRANCE ABSORB registry.

BACKGROUND: Randomized trials comparing the first-generation absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA, USA) with a drug-eluting stent showed a moderate but significant increase in the rate of 3-year major adverse cardiac events and scaffold thrombosis, followed by a decrease in adverse events after 3 years. AIM: The objective of this study was to assess the 5-year outcomes of patients treated with at least one absorb BVS and included in the FRANCE ABSORB registry. METHODS: All patients treated in France with an absorb BVS were prospectively included in a large nationwide multicentre registry. The primary efficacy outcome was the occurrence of 5-year major adverse cardiac events. Secondary efficacy outcomes were the rates of 5-year target vessel revascularization and definite/probable scaffold thrombosis. RESULTS: Between September 2014 and April 2016, 2,070 patients were included in 86 centres (mean age 55±11 years; 80% men; 49% with acute coronary syndrome). The rates of 1-, 3- and 5-year major adverse cardiac events were 3.9%, 9.4% and 12.1%, respectively (including cardiac death in 2.5% and target vessel revascularization in 10.4%). By multivariable analysis, diabetes, oral anticoagulation, the use of multiple Absorb BVSs and the use of a 2.5mm diameter absorb BVS were associated with 5-year major adverse cardiac events. The rates of 1-, 3- and 5-year definite/probable scaffold thrombosis were 1.5%, 3.1% and 3.6%, respectively. By multivariable analysis, older age, diabetes, anticoagulation at discharge and the use of a 2.5mm diameter absorb BVS were associated with 5-year scaffold thrombosis. CONCLUSIONS: Absorb BVS implantation was associated with low rates of 1-year major adverse cardiac events, which increased significantly at 3-year follow-up. There was a clear decrease in the rates of scaffold thrombosis and major adverse cardiac events after 3 years.

Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas.

Cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative disorders that are manageable by immunotherapy. Twenty-one patients were enrolled in a prospective open-label, dose-escalation multicenter study evaluating the effects of repeated TG1042 [adenovirus-interferon (IFN)-gamma] intralesional injections in patients with primary CLs, of which 18 were of T-cell and 3 of B-cell type. Repeated intralesional therapy using TG1042 consistently results in local tumor regressions in about half of treated patients and one-third of patients also in regressions in noninjected distant lesions, likely reflecting the systemic immune activation after intralesional therapy. Treatment was well tolerated with few adverse events including injection site reactions, chills, lymphopenia, and fever. Immune monitoring in the peripheral blood demonstrated systemic immune activation and the induction of antibodies against tumor antigens in some patients without clear association with clinical responses. CLs, in particular B-cell lymphomas with high objective response rates, seem to be excellent targets for this type of immunotherapy.

Percutaneous Myocardial Revascularization in Late-Presenting Patients With STEMI.

BACKGROUND: The optimal management of patients with ST-segment elevation myocardial infarction (STEMI) presenting late->12 hours following symptom onset-is still under debate. OBJECTIVES: The purpose of this study was to describe characteristics, temporal trends, and impact of revascularization in a large population of latecomer STEMI patients. METHODS: The authors analyzed the data of 3 nationwide observational studies from the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting between 12 and 48 hours after symptom onset were classified as latecomers. RESULTS: A total of 6,273 STEMI patients were included in the 3 cohorts, 1,169 (18.6%) of whom were latecomers. After exclusion of patients treated with fibrinolysis and patients deceased within 2 days after admission, 1,077 patients were analyzed, of whom 729 (67.7%) were revascularized within 48 hours after hospital admission. At 30-day follow-up, all-cause death rate was significantly lower among revascularized latecomers (2.1% vs 7.2%; P < 0.001). After a median follow-up of 58 months, the rate of all-cause death was 30.4 (95% CI: 25.7-35.9) per 1,000 patient-years in the revascularized latecomers group vs 78.7 (95% CI: 67.2-92.3) per 1,000 patient-years in the nonrevascularized latecomers group (P < 0.001). In multivariate analysis, revascularization of latecomer STEMI patients was independently associated with a significant reduction of mortality occurrence during follow-up (HR: 0.65 [95% CI: 0.50-0.84]; P = 0.001). CONCLUSIONS: Coronary revascularization of latecomer STEMI patients is associated with better short and long-term clinical outcomes.

Effect of Sex on Outcomes of Coronary Rotational Atherectomy Percutaneous Coronary Intervention (From the European Multicenter Euro4C Registry).

Data regarding the potential influence of gender on outcomes of rotational atherectomy (RA) percutaneous coronary intervention (PCI) are scarce and conflicting. Using the Euro4C registry, an international prospective multicentric registry of RA PCI, we evaluated the influence of gender on clinical outcomes of RA PCI. Between October 2016 and July 2018, 966 patients were included. In them, 267 (27.6%) were females. Female patients were older than males (77.7 years old ± 9.8 vs 73.3 ± 9.5 years old respectively, p < 0.001) had a poorer renal function (43,1% of females had a GFR < 60 ml/min:1.73m² vs 30.4% of males, p < 0.001) and were more frequently admitted for an acute coronary syndrome (32.2% vs 22.3% p = 0.002). During RA procedure, women were less likely to be treated by radial approach (65.0% vs 74.4%, p = 0.004). In-hospital major adverse cardiac event rate-defined as cardiovascular death, myocardial infarction, stroke/transient ischemic attack, target lesion revascularization, and coronary artery bypass grafting surgery-was higher in the female group (7.1% vs 3.7%, p = 0.043). However, coronary perforation, dissection, slow/low flow and tamponade did not significantly differ in gender, neither did cardiovascular medications at discharge. At 1 year follow-up, rate of major adverse cardiac event was 18.4% in the female group vs 11.2% in the male group (adjusted Hazard Ratio 1.82 [1.24 to 2.67], p = 0.002). No significant bleeding differences were observed in gender, neither in hospital, nor during follow-up. In conclusion women had worse clinical outcomes following RA PCI during hospitalization and at 1 year follow-up than did men.

Applicability of the REDUCE-IT trial to the FAST-MI registry. Are the results of randomized trials relevant in routine clinical practice?

BACKGROUND: The reduction of cardiovascular events with icosapent ethyl-intervention trial (REDUCE-IT) trial revealed robust atherosclerotic cardiovascular risk reduction with a strategy comprising high-dose omega-3 icosapent ethyl vs placebo in statin-treated patients with elevated triglycerides and controlled low-density lipoprotein cholesterol (LDL-C). HYPOTHESIS: Are the results of the REDUCE-IT trial applicable to the French registry on acute ST-elevation and non-ST-elevation myocardial infarction (FAST-MI) population? METHODS: Data were extracted from the FAST-MI 2010 and 2015 registries. We applied the REDUCE-IT enrolment criteria (triglycerides 150-500 mg/dL and LDL-C 40-100 mg/dL on statins) to the FAST-MI population in patients aged ≥45 years who had detailed lipid values postacute hospitalization, focusing on their clinical profile and cardiovascular prognosis. RESULTS: Of the 3789 FAST-MI patients with a full lipid profile (median 11.1 [IQR 7.6-17.4] months after hospitalization for myocardial infarction), 472 (12.5%; 95% CI 11.4-13.5) met the eligibility criteria for REDUCE-IT (REDUCE-IT-like group). The cardiovascular event rate (all-cause death, nonfatal myocardial infarction, nonfatal stroke) was 36.7 (95% CI 27.8-48.6) per 1000 person-years for the REDUCE-IT-like group, which compares with the 36.9 (95% CI 26.1-51.5) per 1000 person-years (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) reported in the REDUCE-IT trial. The residual cardiovascular risk related to elevated triglycerides in the REDUCE-IT-like group was similar to the risk in the REDUCE-IT trial. CONCLUSIONS: If the results of REDUCE-IT are applied to patients hospitalized for a myocardial infarction in France, 12.5% of these patients could benefit from a strategy of high-dose omega-3 icosapent ethyl on top of contemporary therapy including statins to improve their clinical outcomes.

Impact of aortic valve calcification severity on device success after transcatheter aortic valve replacement.

Aortic valvular calcium score (AVCS) can identify severe aortic stenosis (AS) and provide powerful prognostic information. In severe and symptomatic AS, patients can be referred for a transcatheter aortic valve replacement (TAVR). The aim of this study was to determine whether AVCS, measured on the preoperative contrast enhanced multislice computed tomography (MSCT), is associated with device success (DS), major adverse cardiac events (MACEs) and paravalvular leak (PVL) after TAVR. Three hundred and fifty-two consecutive patients who underwent TAVR with a preoperative standardised contrast enhanced MSCT were included in the study. Valvular calcification detection was defined by adding + 100 Hounsfield Unit (HU) to mean HU determined by a region of interest placed in the contrast enhanced ascending aorta. AVCS was then indexed to the aortic annulus surface (AVCSi). Endpoints were DS and 30-day MACE according to Valve Academic Research Consortium-2 consensus document, and moderate to severe PVL. DS was obtained for 305 patients. In multivariate analysis, AVCSi was negatively and independently associated with DS: OR = 0.99, 95% CI 0.99-0.99, p = 0.03. In the subgroup analysis, this association was particularly relevant with self-expanding prostheses [n = 151 (43%), p = 0.018] and in the cases of asymmetric calcium valvular distribution [n = 283 (80%), p 0.002]. There was no association between MACE and AVCS (p = 0.953) and AVCSi (p = 0.757). PVL was positively associated with AVCS (p < 0.001) and AVCSi (p < 0.001). In conclusion, in TAVR, AVCS, measured on preoperative contrast enhanced MSCT, is significantly associated with DS and PVL, but not with 30-day MACE. Its routine use could be relevant to appreciate success chances of TAVR.