Reticulated Platelets Predict Cardiovascular Death and Adverse Events in Coronary Artery Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The pro-thrombotic immature or reticulated platelets (RPs) are known to be elevated in high-risk patients and in different pathological settings. It has been shown that RPs correlate with an insufficient antiplatelet response to antiplatelet agents. RPs are emerging novel predictors of adverse cardiovascular events in cardiovascular disease. This study, using the totality of existing evidence, evaluated the prognostic role of RPs in patients with coronary artery disease. METHODS: We performed a systematic review and meta-analysis including trials of acute and chronic coronary syndrome reporting clinical outcomes according to RPs levels in the peripheral blood. We compared patients with elevated RPs (RPshigh) to patients without elevated RPs (RPslow). Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were cardiovascular death, myocardial infarction, ischemic stroke, urgent coronary revascularization and bleedings. RESULTS: A total of 7 studies, including 2213 patients, were included. The risk for MACCE was significantly higher in RPshigh compared to RPslow patients (OR 2.67 [1.87; 3.81], I2 = 43.8%). RPshigh were associated with cardiovascular death (OR 2.09 [1.36; 3.22], I2 = 40.4%). No associations for RPshigh were detected with the other singular components of MACCE: myocardial infarction (OR 1.73 [0.89; 3.38] I2 = 60.5%) and stroke (OR 1.72 [0.59; 4.96] I2 = 21%). The risk of bleeding did not differ between groups(OR 0.58 [0.15; 2.22] I2 = 86.1%). CONCLUSION: Elevated RPs are significantly associated with increased risk of cardiovascular events and cardiovascular death.

Drug-Coated Balloon Angioplasty for De Novo Lesions on the Left Anterior Descending Artery.

BACKGROUND: Drug-coated balloons (DCB) are an emerging tool for modern percutaneous coronary intervention (PCI), but evidence on their use for de novo lesions on large vessels is limited. METHODS: Consecutive patients undergoing DCB-based PCI on the left anterior descending artery in 2 Italian centers from 2018 to 2022 were retrospectively enrolled and compared with patients who received left anterior descending PCI with contemporary drug-eluting stents (DES). In-stent restenosis was excluded. The DCB group included both patients undergoing DCB-only PCI and those receiving hybrid PCI with DCB and DES combined. The primary end point was target lesion failure at 2 years, defined as the composite of target lesion revascularization, cardiac death, and target vessel myocardial infarction. RESULTS: We included 147 consecutive patients undergoing DCB-based treatment on the left anterior descending artery and compared them to 701 patients who received conventional PCI with DES. In the DCB group, 43 patients (29.2%) were treated with DCB only and 104 (70.8%) with a hybrid approach; DCB length was greater than stent length in 55.1% of cases. Total treated length was higher in the DCB group (65 [40-82] versus 56 [46-66] mm; P=0.002), while longer DESs were implanted (38 [24-62] versus 56 [46-66] mm; P<0.001) and a higher rate of large vessels were treated (76.2% versus 83.5%; P=0.036) in the DES cohort. The cumulative 2-year target lesion failure incidence was not significantly different between the 2 groups (DCB, 4.1% versus DES, 9.8%; hazard ratio, 0.51 [95% CI, 0.20-1.27]; P=0.15). After a 1:1 propensity score matching resulting in 139 matched pairs, the DCB-based treatment was associated with a lower risk for target lesion failure at 2 years compared with DES-only PCI (hazard ratio, 0.2 [95% CI, 0.07-0.58]; P=0.003), mainly driven by less target lesion revascularization. CONCLUSIONS: A DCB-based treatment approach for left anterior descending revascularization allows a significantly reduced stent burden, thereby potentially limiting target lesion failure risk at midterm follow-up.

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality. RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead. CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.

Safety and efficacy of an ultra low dose fluoroscopic protocol for chronic total occlusion recanalization.

BACKGROUND: Chronic total occlusion (CTO) revascularization is a major source of radiation for both patients and physicians. Therefore, efforts to minimize radiation during CTO percutaneous coronary intervention (PCI) are highly encouraged. AIMS: To evaluate the impact of an Ultra Low fluoroscopic Dose Protocol (ULDP), based on 3.75 frames per second for the fluoroscopy and 7.5 frames per second for the cine acquisition, during CTO PCI. METHODS: One hundred fifty consecutive patients who underwent CTO PCI were retrospectively enrolled. Eighty-five underwent standard dose protocol (SDP) and 65 ULDP. Radiation exposure and acute clinical outcomes were compared between groups. Results were stratified according to lesion complexity. RESULTS: Patients undergoing ULDP, as compared to those undergoing SDP, showed a significant reduction of kerma area product, both for simple lesions (6861.0 vs. 13236.0 mGy × cm2 ; p = 0.014) and complex lesions (CL) (8865.0 vs. 16618.0 mGy × cm2 ; p < 0.001). Similarly, Air Kerma (AK) was lower when ULDP was used (1222.5 vs. 2015.0 cGy in SL, p = 0.134; 1499.0 vs. 2794.0 cGy in CL, p < 0.001). No significant differences were reported regarding procedural success and in-hospital major adverse cardiovascular events between groups. Notably, there was not any crossover from ULDO to SDP due to poor quality images. Interestingly, fluoroscopy time, procedural time and contrast volume was significantly lower in patients undergoing ULDP only for CLs. CONCLUSIONS: ULDP significantly reduces radiation exposure in the setting of high complexity procedures such as CTO PCI. This reduction seemed to be greater with increased procedural complexity and did not impact acute success or adverse clinical events.

How to predict conduction disturbances after transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVI) has evolved into the gold standard management option for high-risk patients with severe aortic stenosis. Despite identifying procedural, electrocardiographic, and clinical predictors of important post-procedural conduction disturbances (left bundle branch block and high-degree atrioventricular block) and despite continuous technological refinement of transcatheter aortic valves, the rate of post-procedural conduction disturbance remains high and challenging to manage. New strategies are required to reduce the overall rate of post-procedural permanent pacemaker implantations. In this article, we will review the incidence, predictive factors, and clinical implications of conduction disturbances after TAVI.

Specific characteristics of STEMI in COVID-19 patients and their practical implications.

ST-elevation myocardial infarction (STEMI) is one of the cardiac emergencies whose management has been most challenged by the COVID-19 pandemic. Patients presenting with the "lethal combo" of STEMI and concomitant SARS-CoV-2 infection have faced dramatic issues related to the need for self-isolation, systemic inflammation with multi-organ disease and difficulties to obtain timely diagnosis and treatment. The interplay between these and other factors has partly neutralized the major advances in STEMI care achieved in the last decades, significantly impairing prognosis in these patients. In the present review article, we will provide an overview on mechanisms of myocardial injury, specific clinical and angiographic characteristics and contemporary management in different settings of STEMI patients with COVID-19, alongside the inherent implications in terms of in-hospital mortality and short-term clinical outcomes.

Performance of a green wall (Total Value Wall™) at high greywater loading rates and Life Cycle Impact Assessment.

Nature-based greywater (GW) treatment and reuse in urban areas has become an up-and-coming option. A 14.4 m2 green wall system called Total Value Wall (TVW) was installed at a terraced house in Gent (Belgium) for treating GW and reusing the effluent for toilet flushing. In a previous study, the TVW was loaded at 7 L.m-2.d-1 and efficiently removed TSS (67%), COD (43%), BOD5 (83%) and total coliforms (log 2), but a number of issues were reported related to nutrient leaching from the substrate, and the excessive retention time in the storage tanks. In this study results are reported from a follow-up study during which an adapted TVW was subjected to both higher hydraulic and pollutant loading rates in order to investigate the treatment capability of TVW. The design of the system, i.e. substrate contained in geotextile bags, did not sustain the higher hydraulic loading rates as excessive leakage occurred. Despite this, the higher pollutant loading rates still resulted in an acceptable effluent quality with 15 mg.L-1 TSS (90%), 85 mg.L-1 COD (82%), and 15 mg.L-1 BOD5 (95%). Ammonium, E. coli and total coliforms were removed with removal rates of 98%, 63% (0.4 log units), and 36% (0.2 log units), respectively. Finally, a life cycle assessment (LCA) was performed for the TVW with and without treating GW to analyze the environmental burden. The LCA impacts showed that replacing tap water and chemical fertilizer by GW, and the reuse of effluent, have a positive impact. However, the energy use for pumping has a major impact and should be minimized by using an efficient pump and distribution system to reduce the overall footprint.

Polyhydroxyalkanoate (PHA) production via resource recovery from industrial waste streams: A review of techniques and perspectives.

The problem of waste generation in the form of wastewater and solid wastes has caused an urgent, yet persisting, global issue that calls for the development of sustainable treatment and resource recovery technologies. The production of value-added polyhydroxyalkanoates (PHAs) from industrial waste streams has attracted the attention of researchers and process industries because they could replace traditional plastics. PHAs are biopolymers with high degradability, with a variety of applications in the manufacturing sector (e.g. medical equipment, packaging). The aim of this review is to describe the techniques and industrial waste streams that are applied for PHA production. The different enrichment and accumulation techniques that employ mixed microbial communities and carbon recovery from industrial waste streams and various downstream processes were reviewed. PHA yields between 7.6 and 76 wt% were reported for pilot-scale PHA production; while, at the laboratory-scale, yields from PHA accumulation range between 8.6 and 56 wt%. The recent advances in the application of waste streams for PHA production could result in more widely spread PHA production at the industrial scale via its integration into biorefineries for co-generation of PHAs with other added-value products like biohydrogen and biogas.

Prevalence of risk factors for suicide in patients prescribed venlafaxine, fluoxetine, and citalopram.

PURPOSE: Three recent observational studies reported that the risk of fatal overdose is greater with venlafaxine than SSRI use. It is not clear whether patient factors could account for this finding. We evaluated whether risk factors for suicide are more prevalent among patients prescribed venlafaxine than patients prescribed fluoxetine or citalopram. METHODS: Using data from the UK General Practice Research Database (GPRD), we identified patients who were first prescribed any of the three drugs between January 1995 and April 2002. We ascertained risk factors for suicide documented in the 1 year before that first prescription. Separate analyses compared venlafaxine (N = 27 096) and fluoxetine (N = 134 996) cohorts, and venlafaxine and citalopram (N = 52 035) cohorts. RESULTS: Previous suicidal behaviors were documented for 1.0% of the venlafaxine cohort compared to 0.4% of the fluoxetine cohort (OR 2.8, 95%CI: 2.4, 3.2) and 0.4% citalopram cohorts (OR 2.4, 95%CI: 2.0, 2.9). 72.5% of venlafaxine patients had been prescribed at least one other antidepressant compared to 27.6% of fluoxetine (OR 6.9, 95%CI: 6.7, 7.1) and 39.5% of citalopram (OR 4.0, 95%CI: 3.9, 4.2) patients. Venlafaxine patients were also four to six times as likely to have been previously hospitalized for depression. CONCLUSION: In the UK, venlafaxine has been selectively prescribed to a patient population with a higher burden of suicide risk factors than patients prescribed fluoxetine and citalopram. Unless baseline population differences are accounted for, observational studies that compare the risk of suicide in patients receiving these agents may produce biased results.

Circumstances surrounding the first injection experience and their association with future syringe sharing behaviors in young urban injection drug users.

Young injection drug users are at heightened risk for acquisition of blood-borne infections because of their high rates of unsafe injection behaviors, yet there has been little research examining the circumstances surrounding injection drug users' first injection experience ('hit'). We examined the relationship between factors associated with young drug users' first hit and their future syringe sharing behaviors among 420 new initiates to injection drug use (less than 5 years), aged 15-30 years old in urban Baltimore, Maryland. Contingency table analysis and logistic regression were used to determine the association between circumstances surrounding the first hit and recent receptive syringe sharing. Participants were primarily male (58.8%), White (71.2%), and were a median age of 24 years (interquartile range [IQR]: 21-27 years). Adjusting for race, gender, and homelessness, the following variables were independently associated with recent receptive syringe sharing: age at first hit (adjusted odds ratio [AOR] = 0.92 per year increase; 95% confidence interval [CI]: 0.87-0.98), self-injection at initiation (AOR = 0.55; 95% CI: 0.32-0.97) and using a syringe that had previously been used by someone else at first hit (AOR = 2.81; 95% CI: 1.70-4.64). These data suggest that injection-related risk behaviors may be established as early as the onset of injection initiation, supporting the need to educate non-injectors of the harms associated with unsafe injection practices.