Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates ...the cardiovascular system via four specific G-protein-coupled receptors named A
R, A
R, A
R, and A
R. Among them, A
subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A
receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular therapies. Most innovative therapies are mediated by the modulation of adenosine release and/or the activation of the A
receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A
receptor, which seems a promising biomarker for a diagnostic and/or a therapeutic tool for the screening and management of coronary artery disease. Finally, a recent class of selective adenosine receptor ligands has emerged, and A
receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease ...risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
BackgroundMyocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids ...as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST.MethodsThis case–control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca’s criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not.ResultsA total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005).ConclusionThe need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.
The hidden side of oral thrombin inhibitors Barraud, Jeremie; Gaubert, Mélanie; Resseguier, Noémie ...
International journal of cardiology,
01/2019, Volume:
274
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and ...related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R
2
= 0.66
P
< 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Guidelines recommend a ticagrelor loading dose (LD) before PCI or a prasugrel LD at the time of percutaneous coronary intervention (PCI) in intermediate and high-risk non–ST-elevation acute coronary ...syndrome (NSTE-ACS). However, achieving an optimal PR inhibition at the time of PCI is critical to prevent adverse events and depends on the timing of LD intake in relation to PCI. We aimed to compare the rate of myonecrosis related to PCI in patients with NSTE-ACS receiving ticagrelor pretreatment versus prasugrel at the time of intervention. We prospectively randomized 213 patients with NSTE-ACS to a 180 mg of ticagrelor LD given as soon as possible after admission and before PCI or to a 60 mg LD of prasugrel given at the time of PCI. The primary end point was the rate of periprocedural myonecrosis as defined by an increase of >5 times the ninety-ninth percentiles in troponin-negative patients or a 20% increase in troponin-positive patients. The 2 groups were similar regarding baseline characteristics including clinical setting (p = 0.2). Procedural characteristics were also identical including the number of treated vessels and stenting procedures. Patients in the prasugrel group more often required emergent PCI (p = 0.001). Patients in the ticagrelor group had less periprocedural myonecrosis compared with those in the prasugrel group (19.8% vs 38.3%; p = 0.03). The rate of major adverse cardiovascular events and Bleeding Academic Research Consortium ≥2 at 1-month follow-up was low and similar between the 2 groups. In conclusion, a ticagrelor LD as soon as possible before PCI is superior to prasugrel at the time of PCI to prevent periprocedural myonecrosis in NSTE-ACS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cardiogenic shock is a complex clinical entity associated with very high mortality and intensive resource utilization. Despite the widespread use of timely reperfusion and appropriate ...pharmacotherapy, the survival rate remains at around 50%. Recently, percutaneous axial flow pumps have been integrated into the therapeutic spectrum of cardiogenic shock management. However, most of the literature supporting their use stems from observational studies. To date, attempts to perform randomized controlled trials with percutaneous axial flow pumps have failed. This underlines the challenge of performing a well-conducted randomized controlled trial that provides the highest level of evidence. Such a trial is warranted, because percutaneous axial flow pumps are costly, and are associated with serious complications. The major pitfalls of previous studies were lack of standardized cardiogenic shock definitions according to clinical severity, inappropriate patient and device selection, lack of standardized trial endpoints and high rates of crossovers; these issues must be carefully considered and evaluated. In light of recent trial failures, we aim to summarize the challenges associated with performing randomized controlled trials of percutaneous axial flow pumps in patients experiencing acute myocardial infarction complicated by cardiogenic shock, and to suggest potential means of overcoming them.
Le choc cardiogénique reste une entité clinique complexe associée avec une très haute mortalité et une utilisation intensive de ressource. Malgré la généralisation de la reperfusion précoce et un traitement adapté, le taux de mortalité reste élevée aux alentours de 50 %. Les pompes axiales percutanées ont été récemment intégrées dans l’arsenal thérapeutique du choc cardiogénique. Cependant, la plupart des données de la littérature en faveur de leur utilisation sont de natures observationnelles. À ce jour, les tentatives de réaliser les études cliniques randomisées ont été des échecs. Cela souligne à quel point il reste compliqué de réaliser une étude randomisée bien conduite afin de fournir un niveau de preuve suffisant. Une telle étude est nécessaire car les pompes axiales sont coûteuses et associées avec des complications sérieuses. L’absence de définition standardisée du choc cardiogénique en fonction de sa gravité, une mauvaise sélection des patients ou des interventions, l’absence de critère de jugement validé et le fort taux de crossover sont parmi les écueils majeurs de la réalisation des précédentes études et doivent être prise en compte pour la réalisation des prochaines. À la lumière des échecs récents, nous avons voulu résumer les écueils pour la réalisation d’une étude randomisée utilisant les pompes microaxiales dans le choc cardiogénique secondaire à un IDM et suggérer des voies potentielles de résolution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We sought to compare outcomes and costs of a stepwise approach to transvenous lead extraction (TLE) involving laser-assisted sheaths or mechanical polypropylene sheaths, with/without crossover.
We ...prospectively included patients who underwent TLE (between August 2013 and December 2014) as part of a stepwise approach involving simple traction, lead snaring, and sheath-assisted dissection; all of these patients underwent a first-line polypropylene-sheath-extraction approach (Group A). The comparison group (Group B) was consecutive patients who had undergone TLE before August 2013, during which laser-assisted sheath extraction was the first-line approach. The number of patients in Group B was adjusted to match the number who eventually needed sheaths in Group A. Procedural data, outcomes, and costs were compared between groups (comparison of approaches) and in patients who needed sheath-assisted extraction (comparison of techniques). Overall, 521 leads were extracted (131 patients in Group A, 104 in Group B). Radiological and clinical success rates were similar; crossover from polypropylene to laser sheaths was needed in 10 patients in Group A (vs. none in Group B). Radiological (P< 0.001) and clinical (P= 0.01) success rates were higher and were achieved with a lower radiation exposure (P= 0.03) with laser sheaths in patients (60 in each group) who needed sheath-assisted extraction. Complication rates were similar in both groups (P= 0.66) but two deaths occurred in Group B. The laser approach had higher material cost (P= 0.002).
Although laser-assisted TLE was more effective than polypropylene sheath-assisted TLE, the latter was associated with fewer complications and was more cost-effective.
The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS ...patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI. HP were measured before the administration of any inotrope or vasopressor. Systemic Vascular Resistances index (SVRi), Cardiac Index (CI), and Cardiac Power Index (CPI) were measured by trans-thoracic Doppler echocardiography on admission. Among 37 CS patients, 28 had CS secondary to ADCHF or AMI and were prospectively included. The two groups were similar in terms of demographic data and shock severity criteria. AMI CS was associated with lower SVRi compared to CS related to ADCHF: 2010 (interquartile range (IQR): 1895–2277) vs. 2622 (2264–2993) dynes-s·cm−5·m−2 (p = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88–2.18) vs. 1.78 (1.65–1.96) L·min−1·m−2 (p = 0.067) in AMICS compared to ADCHF. CS patients had different HP according to their etiologies. AMICS had lower SVR and tended to have a higher CI compared to ADHF CS. These differences should be taken into account for patient selection in future research.
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