Perceptions and Expectations of Youth Regarding the Respect for Their Rights in the Hospital.

Information obtained from children themselves regarding the characteristics of the ideal hospital that ensure well-being during a hospital stay is scarce. Here, we report the opinions, perceptions, and expectations of 700 children and adolescents about their experiences, assessed through a mixed-method research approach with age-appropriate questionnaires, three open-ended questions, and an analysis of optional pictorial and textual narratives. Most children indicated that, while they acknowledged the expertise of hospital staff, they also noted several shortcomings, e.g., insufficiently understandable medical information as well as emotional and cognitive support. The continuity of schooling and the right to suffer as little as possible were also critical issues. Adolescents valued in particular the quality of care and services provided, the hospital's adherence to equality and non-discrimination rights, and protection systems but negatively perceived several aspects related to play and participation. Significant differences in the co-occurrences of the most frequently used text terms with the keywords "hospital" and "child/adolescent" between age groups highlight variations in the way patients perceive and articulate their experiences within the hospital setting depending on the cognitive processes linked to age. In drawings, prevailing attention was placed on the physical context of the hospital room, with figures expressing mostly negative emotions. Specifically, in this regard, the main emotion in children was sadness, and, in adolescents, it was fear. Overall, these insights are pivotal in the context of our research objectives as they shed light on the nuanced preferences, needs, and perspectives of children and adolescents during their hospital stays. Recognizing the identified shortcomings, we propose recommendations emphasizing the improvement of medical communication clarity, enhancement of emotional and cognitive support, and the improvement of programs to avoid instructional gaps during hospital stays. Addressing these specific needs is critical for a more comprehensive approach to pediatric healthcare provision.

Antiplatelet Strategies for Older Patients with Acute Coronary Syndromes: Finding Directions in a Low-Evidence Field.

Patients ≥ 75 years of age account for about one third of hospitalizations for acute coronary syndromes (ACS). Since the latest European Society of Cardiology guidelines recommend that older ACS patients use the same diagnostic and interventional strategies used by the younger ones, most elderly patients are currently treated invasively. Therefore, an appropriate dual antiplatelet therapy (DAPT) is indicated as part of the secondary prevention strategy to be implemented in such patients. The choice of the composition and duration of DAPT should be tailored on an individual basis, after careful assessment of the thrombotic and bleeding risk of each patient. Advanced age is a main risk factor for bleeding. Recent data show that in patients of high bleeding risk short DAPT (1 to 3 months) is associated with decreased bleeding complications and similar thrombotic events, as compared to standard 12-month DAPT. Clopidogrel seems the preferable P2Y12 inhibitor, due to a better safety profile than ticagrelor. When the bleeding risk is associated with a high thrombotic risk (a circumstance present in about two thirds of older ACS patients) it is important to tailor the treatment by taking into account the fact that the thrombotic risk is high during the first months after the index event and then wanes gradually over time, whereas the bleeding risk remains constant. Under these circumstances, a de-escalation strategy seems reasonable, starting with DAPT that includes aspirin and low-dose prasugrel (a more potent and reliable P2Y12 inhibitor than clopidogrel) then switching after 2-3 months to DAPT with aspirin and clopidogrel for up to 12 months.

Percutaneous left atrial appendage occlusion in a frail, high-risk, octogenarian patient population, after having undergone transcatheter aortic valve implantation.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) represents an alternative stroke prevention method in patients with atrial fibrillation and an increased bleeding risk, chronic kidney disease or contraindications to oral anticoagulants. Aim of our study was to evaluate the feasibility and safety of percutaneous LAAO in high-risk, frail patients having undergone transcatheter aortic valve implantation (TAVI). METHODS: Thirty-one patients having undergone TAVI and scheduled for LAAO were prospectively included in our study. RESULTS: Implantation was successful in 29 of 31 cases (93.5%).There were no patients that developed a major acute cardiovascular event, stroke, or device dislocation/embolization. There was a single case of major bleeding (3.2%) and 3 cases of acute kidney injury (9.7%). At 3 months, no patients experienced a stroke, one patient had a device-related thrombus (3.4%), one patient showed a significant peri-device leak, and one patient had a persistent iatrogenic atrial septal defect. CONCLUSIONS: Our study shows that percutaneous LAAO may represent a feasible alternative strategy for stroke prevention, that can be safely performed in high-risk, multimorbid patients with high bleeding risk or contraindications to oral anticoagulation.

Pregnenolone-methyl-ether enhances CLIP170 and microtubule functions improving spine maturation and hippocampal deficits related to CDKL5 deficiency.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a neurodevelopmental disease characterized by severe infantile seizures and intellectual disability. The absence of CDKL5 in mice causes defective spine maturation that can at least partially explain the cognitive impairment in CDKL5 patients and CDD mouse models. The molecular basis for such defect may depend on the capacity of CDKL5 to regulate microtubule (MT) dynamics through its association with the MT-plus end tracking protein CLIP170 (cytoplasmic linker protein 170). Indeed, we here demonstrate that the absence of CDKL5 causes CLIP170 to be mainly in a closed inactive conformation that impedes its binding to MTs. Previously, the synthetic pregnenolone analogue, pregnenolone-methyl-ether (PME), was found to have a positive effect on CDKL5-related cellular and neuronal defects in vitro. Here, we show that PME induces the open active conformation of CLIP170 and promotes the entry of MTs into dendritic spines in vitro. Furthermore, the administration of PME to symptomatic Cdkl5-knock-out mice improved hippocampal-dependent behavior and restored spine maturation and the localization of MT-related proteins in the synaptic compartment. The positive effect on cognitive deficits persisted for 1 week after treatment withdrawal. Altogether, our results suggest that CDKL5 regulates spine maturation and cognitive processes through its control of CLIP170 and MT dynamics, which may represent a novel target for the development of disease-modifying therapies.

Early hemodynamic changes after transcatheter aortic valve implantation in patients with severe aortic stenosis measured by invasive pressure volume loop analysis.

Replacement of a stenotic aortic valve reduces immediately the ventricular to aortic gradient and is expected to improve diastolic and systolic left ventricular function over the long term. However, the hemodynamic changes immediately after valve implantation are so far poorly understood. Within this pilot study, we performed an invasive pressure volume loop analysis to describe the early hemodynamic changes after transcatheter aortic valve implantation (TAVI) with self-expandable prostheses. Invasive left ventricular pressure volume loop analysis was performed in 8 patients with aortic stenosis (mean 81.3 years) prior and immediately after transfemoral TAVI with a self-expandable valve system (St. Jude Medical Portico Valve). Parameters for global hemodynamics, afterload, contractility and the interaction of the cardiovascular system were analyzed. Left ventricular ejection fraction, (53.9% vs. 44.8%, p = 0.018), preload recruitable stroke work (68.5 vs. 44.8 mmHg, p = 0.012) and end-systolic elastance (3.55 vs. 2.17, p = 0.036) both marker for myocardial contractility declined significantly compared to baseline. As sign of impaired diastolic function, TAU, a preload-independent measure of isovolumic relaxation (37.3 vs. 41.8 ms, p = 0.018) and end-diastolic pressure (13.1 vs. 16.4 mmHg, p = 0.015) raised after valve implantation. Contrarily, a smaller ratio of end-systolic to arterial elastance (ventricular-arterial coupling) indicates an improvement of global cardiovascular energy efficiency (1.40 vs. 0.97 p = 0.036). Arterial elastance had a strong correlation with the number of conducted rapid ventricular pacings (Pearson correlation coefficient, r = 0.772, p = 0.025). Invasive left ventricular pressure volume loop analysis revealed impaired systolic and diastolic function in the early phase after TAVI with self-expandable valve for the treatment of severe aortic stenosis. Contrarily, we found indications for early improvement of global cardiovascular energy efficiency.

Management of acute coronary syndromes in older adults.

Older patients are underrepresented in prospective studies and randomized clinical trials of acute coronary syndromes (ACS). Over the last decade, a few specific trials have been conducted in this population, allowing more evidence-based management. Older adults are a heterogeneous, complex, and high-risk group whose management requires a multidimensional clinical approach beyond coronary anatomic variables. This review focuses on available data informing evidence-based interventional and pharmacological approaches for older adults with ACS, including guideline-directed management. Overall, an invasive approach appears to demonstrate a better benefit-risk ratio compared to a conservative one across the ACS spectrum, even considering patients' clinical complexity and multiple comorbidities. Conversely, more powerful strategies of antithrombotic therapy for secondary prevention have been associated with increased bleeding events and no benefit in terms of mortality reduction. An interdisciplinary evaluation with geriatric assessment should always be considered to achieve a holistic approach and optimize any treatment on the basis of the underlying biological vulnerability.

Loss of CDKL5 Causes Synaptic GABAergic Defects That Can Be Restored with the Neuroactive Steroid Pregnenolone-Methyl-Ether.

CDKL5 deficiency disorder (CDD) is an X-linked neurodevelopmental disorder characterised by early-onset drug-resistant epilepsy and impaired cognitive and motor skills. CDD is caused by mutations in cyclin-dependent kinase-like 5 (CDKL5), which plays a well-known role in regulating excitatory neurotransmission, while its effect on neuronal inhibition has been poorly investigated. We explored the potential role of CDKL5 in the inhibitory compartment in Cdkl5-KO male mice and primary hippocampal neurons and found that CDKL5 interacts with gephyrin and collybistin, two crucial organisers of the inhibitory postsynaptic sites. Through molecular and electrophysiological approaches, we demonstrated that CDKL5 loss causes a reduced number of gephyrin puncta and surface exposed γ2 subunit-containing GABAA receptors, impacting the frequency of miniature inhibitory postsynaptic currents, which we ascribe to a postsynaptic function of CDKL5. In line with previous data showing that CDKL5 loss impacts microtubule (MT) dynamics, we showed that treatment with pregnenolone-methyl-ether (PME), which promotes MT dynamics, rescues the above defects. The impact of CDKL5 deficiency on inhibitory neurotransmission might explain the presence of drug-resistant epilepsy and cognitive defects in CDD patients. Moreover, our results may pave the way for drug-based therapies that could bypass the need for CDKL5 and provide effective therapeutic strategies for CDD patients.

Association of Sex with Outcome in Elderly Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Worse outcomes have been reported for women, compared with men, after an acute coronary syndrome (ACS). Whether this difference persists in elderly patients undergoing similar invasive treatment has not been studied. We investigated sex-related differences in 1-year outcome of elderly acute coronary syndrome patients treated by percutaneous coronary intervention (PCI). METHODS: Patients 75 years and older successfully treated with PCI were selected among those enrolled in 3 Italian multicenter studies. Cox regression analysis was used to assess the independent predictive value of sex on outcome at 12-month follow-up. RESULTS: A total of 2035 patients (44% women) were included. Women were older and most likely to present with ST-elevation myocardial infarction (STEMI), diabetes, hypertension, and renal dysfunction; men were more frequently overweight, with multivessel coronary disease, prior myocardial infarction, and revascularizations. Overall, no sex disparity was found about all-cause (8.3% vs 7%, P = .305) and cardiovascular mortality (5.7% vs 4.1%, P = .113). Higher cardiovascular mortality was observed in women after STEMI (8.8%) vs 5%, P = .041), but not after non ST-elevation-ACS (3.5% vs 3.7%, P = .999). A sensitivity analysis excluding patients with prior coronary events (N = 1324, 48% women) showed a significantly higher cardiovascular death in women (5.4% vs 2.9%, P = .025). After adjustment for baseline clinical variables, female sex did not predict adverse outcome. CONCLUSIONS: Elderly men and women with ACS show different clinical presentation and baseline risk profile. After successful PCI, unadjusted 1-year cardiovascular mortality was significantly higher in women with STEMI and in those with a first coronary event. However, female sex did not predict cardiovascular mortality after adjustment for the different baseline variables.

Dynamics of cerebral oxygenation during rapid ventricular pacing and its impact on outcome in transfemoral transcatheter aortic valve implantation.

BACKGROUND: Cerebral O2 saturation (ScO2 ) reflects cerebral perfusion and can be measured noninvasively by near-infrared spectroscopy (NIRS). OBJECTIVES: In this pilot study, we describe the dynamics of ScO2 during TAVI in nonventilated patients and its impact on procedural outcome. METHODS AND RESULTS: We measured ScO2 of both frontal lobes continuously by NIRS in 50 consecutive analgo-sedated patients undergoing transfemoral TAVI (female 58%, mean age 80.8 years). Compared to baseline ScO2 dropped significantly during RVP (59.3% vs. 53.9%, p < .01). Five minutes after RVP ScO2 values normalized (post RVP 62.6% vs. 53.9% during RVP, p < .01; pre 61.6% vs. post RVP 62.6%, p = .53). Patients with an intraprocedural pathological ScO2 decline of >20% (n = 13) had higher EuroSCORE II (3.42% vs. 5.7%, p = .020) and experienced more often delirium (24% vs. 62%, p = .015) and stroke (0% vs. 23%, p < .01) after TAVI. Multivariable logistic regression revealed higher age and large ScO2 drops as independent risk factors for delirium. CONCLUSIONS: During RVP ScO2 significantly declined compared to baseline. A ScO2 decline of >20% is associated with a higher incidence of delirium and stroke and a valid cut-off value to screen for these complications. NIRS measurement during TAVI procedure may be an easy to implement diagnostic tool to detect patients at high risks for cerebrovascular complications and delirium.

Value of prognostic nutritional index for survival prediction in trans-catheter aortic valve replacement compared to other common nutritional indexes.

BACKGROUND: Nutritional status predicts outcomes after TAVR. Predictive value of Prognostic Nutritional Index (PNI) was investigated in patients undergoing TAVR, and compared to other nutritional indexes. METHODS: A cohort of 114 patients undergoing TAVR in a high-volume centre was studied. A prospective 1-year follow-up was completed. PNI was estimated as follows: (10 × serum albumin[g/dl])+(0.005 × total lymphocytes [1000/µl]). One-year survival was compared in patients with PNI above vs below median; Kaplan-Meier curves were created. A multivariate analysis was used to assess predictive value of PNI for 1-year mortality. ROC curves were used to assess discrimination by PNI, and to compare it with Geriatric Nutritional Risk Index (GNRI) and Body Mass Index (BMI). RESULTS: Mean age was 82.2 years, 59.6% were male. Mean PNI was 46 ± 5. Pre-procedurally, no differences were found between patients with high vs. low PNI. One-year mortality was significantly higher in patients with low PNI values (19/57 vs. 4/57; p < .001). Complications did not differ. A higher PNI predicted 1-year survival, even after adjusting for clinical factors (model 1: HR 0.8, 95% CI 0.7-0.9, p < .0001) and laboratory parameters (NT-proBNP, IL-6, CRP, eGFR, cystatin C, haemoglobin) (model 2: HR 0.8, 95% CI 0.7-0.9, p < .05). ROC curves revealed a stronger predictive value for PNI (AUC 0.80) compared to GNRI (0.77) and BMI (0.6). The optimal cut-off for PNI was 45. CONCLUSION: PNI is a useful and practical nutritional marker reflecting malnutrition and inflammation prior to the intervention, and strongly predicts 1-year survival. PNI seems to be a better prognostic marker than BMI or GNRI after TAVR.

Thirty-day incidence of stroke after transfemoral transcatheter aortic valve implantation: meta-analysis and mixt-treatment comparison of self-expandable versus balloon-expandable valve prostheses.

AIMS: Stroke is a major complication after transcatheter aortic valve implantation (TAVI). Although multifactorial, it remains unknown whether the valve deployment system itself has an impact on the incidence of early stroke. We performed a meta- and network analysis to investigate the 30-day stroke incidence of self-expandable (SEV) and balloon-expandable (BEV) valves after transfemoral TAVI. METHODS AND RESULTS: Overall, 2723 articles were searched directly comparing the performance of SEV and BEV after transfemoral TAVI, from which 9 were included (3086 patients). Random effects models were used for meta- and network meta-analysis based on a frequentist framework. Thirty-day incidence of stroke was 1.8% in SEV and 3.1% in BEV (risk ratio of 0.62, 95% confidence interval (CI) 0.49-0.80, p = 0.004). Treatment ranking based on network analysis (P-score) revealed CoreValve with the best performance for 30-day stroke incidence (75.2%), whereas SAPIEN had the worst (19.0%). However, network analysis showed no inferiority of SAPIEN compared with CoreValve (odds ratio 2.24, 95% CI 0.70-7.2). CONCLUSION: Our analysis indicates higher 30-day stroke incidence after transfemoral TAVI with BEV compared to SEV. We could not find evidence for superiority of a specific valve system. More randomized controlled trials with head-to-head comparison of SEV and BEV are needed to address this open question.

Bleeding risk prediction in elderly patients managed invasively for acute coronary syndromes: External validation of the PRECISE-DAPT and PARIS scores.

BACKGROUND: We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management. METHODS: Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials. RESULTS: After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3-5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ2 > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%. CONCLUSIONS: In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.

Potential Role and Prognostic Value of Erythropoietin Levels in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Background: Both EPO levels and anemia have shown prognostic value in several cardiac disorders. An observational study with a prospective follow-up was performed to investigate their independent prognostic roles in severe aortic stenosis. Methods: An up to 36-month follow-up of consecutive patients with severe aortic stenosis undergoing TAVR in a high-volume center was performed. Patients with eGRF <30 mL/min/1.73 m2 were excluded. EPO levels and/or anemia status and its association with mid-term mortality were assessed. Results: Out of 407, 360 met eligibility criteria. Median age was 83 years, with 71.4% having a NYHA class III/IV. Anemia was present in 51.9%, and iron deficiency in 52.8%. Median (IQR) EPO levels were 14.4 (9.30-24.30) mIU/mL. Median follow-up was 566 days. Anemia was associated with overall mortality (HR 2.40, 95% CI 1.51-3.80, p < 0.001). Higher logEPO levels were associated with mid-term mortality (HR 4.05, 95% CI 2.29-7.16, p < 0.001), even after adjusting for clinically and/or statistically relevant factors (multivariate HR 2.25, 95 CI 1.09-4.66, p = 0.029). Kaplan-Meier analyses showed early diverging curves for anemia vs. non-anemia, whereas curves for patients in various EPO level quartiles started to diverge at about 100 days, with differences consistently increasing during the subsequent entire follow-up period. Conclusions: Differently from anemia, which was a strong predictor for both early and late mortality in severe aortic stenosis after TAVR, independent prognostic value of EPO only emerged after post-TAVR recovery. EPO prognostic value was independent from anemia and mild-to-moderate renal dysfunction. High EPO levels could be useful to identify patients with severe aortic stenosis showing a compromised mid-term survival in spite of TAVR use and independently from early TAVR results.

Inflammatory signatures are associated with increased mortality after transfemoral transcatheter aortic valve implantation.

AIMS: Systemic inflammatory response, identified by increased total leucocyte counts, was shown to be a strong predictor of mortality after transcatheter aortic valve implantation (TAVI). Yet the mechanisms of inflammation-associated poor outcome after TAVI are unclear. Therefore, the present study aimed at investigating individual inflammatory signatures and functional heterogeneity of circulating myeloid and T-lymphocyte subsets and their impact on 1 year survival in a single-centre cohort of patients with severe aortic stenosis undergoing TAVI. METHODS AND RESULTS: One hundred twenty-nine consecutive patients with severe symptomatic aortic stenosis admitted for transfemoral TAVI were included. Blood samples were obtained at baseline, immediately after, and 24 h and 3 days after TAVI, and these were analysed for inflammatory and cardiac biomarkers. Myeloid and T-lymphocyte subsets were measured using flow cytometry. The inflammatory parameters were first analysed as continuous variables; and in case of association with outcome and area under receiver operating characteristic (ROC) curve (AUC) ≥ 0.6, the values were dichotomized using optimal cut-off points. Several baseline inflammatory parameters, including high-sensitivity C-reactive protein (hsCRP; HR = 1.37, 95% CI: 1.15-1.63; P < 0.0001) and IL-6 (HR = 1.02, 95% CI: 1.01-1.03; P = 0.003), lower counts of Th2 (HR = 0.95, 95% CI: 0.91-0.99; P = 0.009), and increased percentages of Th17 cells (HR = 1.19, 95% CI: 1.02-1.38; P = 0.024) were associated with 12 month all-cause mortality. Among postprocedural parameters, only increased post-TAVI counts of non-classical monocytes immediately after TAVI were predictive of outcome (HR = 1.03, 95% CI: 1.01-1.05; P = 0.003). The occurrence of SIRS criteria within 48 h post-TAVI showed no significant association with 12 month mortality (HR = 0.57, 95% CI: 0.13-2.43, P = 0.45). In multivariate analysis of discrete or dichotomized clinical and inflammatory variables, the presence of diabetes mellitus (HR = 3.50; 95% CI: 1.42-8.62; P = 0.006), low left ventricular (LV) ejection fraction (HR = 3.16; 95% CI: 1.35-7.39; P = 0.008), increased baseline hsCRP (HR = 5.22; 95% CI: 2.09-13.01; P < 0.0001), and low baseline Th2 cell counts (HR = 8.83; 95% CI: 3.02-25.80) were significant predictors of death. The prognostic value of the linear prediction score calculated of these parameters was superior to the Society of Thoracic Surgeons score (AUC: 0.88; 95% CI: 0.78-0.99 vs. 0.75; 95% CI: 0.64-0.86, respectively; P = 0.036). Finally, when analysing LV remodelling outcomes, ROC curve analysis revealed that low numbers of Tregs (P = 0.017; AUC: 0.69) and increased Th17/Treg ratio (P = 0.012; AUC: 0.70) were predictive of adverse remodelling after TAVI. CONCLUSIONS: Our findings demonstrate an association of specific pre-existing inflammatory phenotypes with increased mortality and adverse LV remodelling after TAVI. Distinct monocyte and T-cell signatures might provide additive biomarkers to improve pre-procedural risk stratification in patients referred to TAVI for severe aortic stenosis.

Impact of renal dysfunction and acute kidney injury on outcome in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities. AIM: The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. METHODS: Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft-Gault formula ([(140-age) × body weight × 0.85 if female]/(72 × serum creatinine)* 1.73 m2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m2), moderate (eGFR 30-59 ml/min/1.73 m2) or severe (eGFR <30 ml/min/1.73 m2) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months. RESULTS: A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates (P < 0.001) of all-cause (4.5%, 7.5% and 17.8% in patients with none or mild, moderate and severe renal dysfunction, respectively) and cardiovascular mortality (2.8%, 5.2% and 10.2%, respectively). After multivariable adjustment, severe renal dysfunction was associated with a higher risk of all-cause (hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.52-5.37, P = 0.001) and cardiovascular death (HR 3.11, 95% CI 1.41-6.83, P = 0.005), whereas non-fatal events were unaffected. Acute kidney injury incidence was significantly higher in ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome patients (11.7% vs. 7.8%, P = 0.036) and in those with reduced baseline renal function (P < 0.001), and it was associated with increased mortality independently from baseline renal function and clinical presentation. CONCLUSIONS: Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality.

Characteristics and Outcome of Patients ≥75 Years of Age With Prior Coronary Artery Bypass Grafting Admitted for an Acute Coronary Syndrome.

The prognostic role of previous coronary artery bypass (CABG) in elderly patients admitted to hospital for an acute coronary syndrome (ACS) is unclear. Therefore, the aim of this study was to compare the prognosis of patients aged ≥75 years admitted for an ACS with or without previous history of CABG. The primary outcome of the study was a composite of overall mortality, recurrent nonfatal myocardial infarction, nonfatal stroke, and rehospitalization for heart failure at 1-year follow-up. We included 2,253 ACS patients, aged 81 (78 to 85) years enrolled in 3 multicenter studies (the Italian Elderly ACS study, the LADIES ACS study, and the Elderly ACS 2 randomised trial) - 178 (7.9%) with previous CABG, 2,075 (92.1%) without. Patients with previous CABG had a higher burden of cardiovascular risk factors, lower ejection fraction, and higher creatinine values on admission. However, both at univariate analysis and after adjustment for the most relevant covariates (sex, age, previous myocardial infarction, type of ACS, left ventricular ejection fraction, and serum creatinine on admission), previous CABG did not show any statistically significant association with 1-year outcome (adjusted hazard ratio 0.85; 95% confidence interval 0.61 to 1.19; p = 0.353). In conclusion, our study suggests that elderly ACS patients with previous CABG have worse basal clinical characteristics. Nevertheless, in a broad cohort of patients mostly treated with percutaneous coronary intervention during the index event, previous CABG did not confer independent additional risk of major adverse cardiovascular events at 1-year follow-up.

Hemodynamic Outcome and Valve Durability Beyond Five Years After Transcatheter Aortic Valve Replacement.

OBJECTIVE: The aim of this study was to evaluate hemodynamic outcome, structural valve deterioration, and bioprosthetic valve failure beyond 5 years after transcatheter aortic valve replacement (TAVR). METHODS: Demographic, procedural, and outcome data were obtained from all patients treated with TAVR at our institution from 2006 to 2012. We included all patients with echocardiographic data at baseline and with a follow-up echocardiography more than 5 years after TAVR. Standardized definitions were used to assess durability of transcatheter aortic valves. RESULTS: A total of 452 patients were treated with apical or transfemoral transcatheter aortic valve implantation (TAVI) from 2006-2012, and 103 (23%) patients were still alive more than 5 years post TAVI. Mean duration of follow-up was 7.0 ± 0.9 years, with a maximum duration of 9.8 years. Seventy-nine of the 103 patients (76.7%) underwent follow-up echocardiography. Mean aortic gradient decreased from 51.8 ± 14.3 mm Hg before TAVR to 11.7 ± 5.8 mm Hg after TAVR (P<.001), and remained stable at 10.6 ± 6.3 mm Hg during late follow-up (P=.26). Bioprosthetic valve failure occurred in 3 patients (3.8%); two of these patients required reintervention. Seven patients (8.9%) had moderate structural valve deterioration, and 1 patient (1.3%) had severe structural valve deterioration. CONCLUSION: TAVR with self-expanding and balloon-expandable valves appears to be a long-lasting treatment strategy for severe aortic stenosis with excellent long-term hemodynamic function and very low incidence of structural valve deterioration and bioprosthetic valve failure.

De-escalating dual antiplatelet therapy in patients with acute coronary syndromes: the right strategy to harmonize time-dependent ischemic and bleeding risk in elderly patients?

: The European Society of Cardiology guidelines for myocardial revascularization state that de-escalation of P2Y12 inhibitor treatment guided by platelet function testing may be considered for acute coronary syndrome (ACS) patients deemed unsuitable for 12-month potent platelet inhibition. De-escalation strategy aim is to harmonize the time-dependency of thrombotic risk, which is high in the first month after ACS, then decreases exponentially, with bleeding risk, which tends to remain more stable after the procedure-related peak. Harmonizing time-dependency of clinical events may be particularly relevant in those at high risk, such as the elderly patients with ACS in whom an individualized antiplatelet therapy may be more appropriate than a 'one-size-fits all' approach. In this review, we outline the current medical evidence on the topic of dual antiplatelet therapy de-escalation. In addition, we include insights from the Elderly ACS 2 study and recently published post-hoc analyses conducted by the authors' consortium, which further expands current knowledge.

Impact of renal dysfunction and acute kidney injury on outcome in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities. AIM: The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. METHODS: Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft-Gault formula ([(140-age) × body weight × 0.85 if female]/(72 × serum creatinine)* 1.73 m2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m2), moderate (eGFR 30-59 ml/min/1.73 m2) or severe (eGFR <30 ml/min/1.73 m2) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months. RESULTS: A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates (P < 0.001) of all-cause (4.5%, 7.5% and 17.8% in patients with none or mild, moderate and severe renal dysfunction, respectively) and cardiovascular mortality (2.8%, 5.2% and 10.2%, respectively). After multivariable adjustment, severe renal dysfunction was associated with a higher risk of all-cause (hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.52-5.37, P = 0.001) and cardiovascular death (HR 3.11, 95% CI 1.41-6.83, P = 0.005), whereas non-fatal events were unaffected. Acute kidney injury incidence was significantly higher in ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome patients (11.7% vs. 7.8%, P = 0.036) and in those with reduced baseline renal function (P < 0.001), and it was associated with increased mortality independently from baseline renal function and clinical presentation. CONCLUSIONS: Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality.

Short-term decrease of left atrial size predicts clinical outcome in patients with severe aortic stenosis undergoing TAVR.

OBJECTIVES: We investigated whether transcatheter aortic valve replacement (TAVR) results in a short-term decrease in left atrium (LA) size and whether such decrease may predict patients' clinical outcome. BACKGROUND: Increased LA size is a hallmark of severe aortic stenosis (AS) and is associated with adverse patients' cardiovascular outcome. Whether TAVR may lead to a decrease in LA size is not known. METHODS AND RESULTS: Hundred and four patients with severe symptomatic AS and dilated LA undergoing TAVR were enrolled. LA volume was assessed by echocardiography before and shortly after TAVR (median time: 7 days). Composite rate of death and hospitalization for acutely decompensated heart failure (HF) was recorded and clinical status was assessed through NYHA-class evaluation at 12 months median follow-up. After TAVR, 49 patients (47%) demonstrated a decrease in LA volume. Despite a similar baseline NYHA class, patients with decrease in LA size had significant better improvement in clinical status respect to patients with unvaried LA size (NYHA post: 1.2 ± 0.6 vs. 1.8 ± 1.1, p = .001; NYHA reduction: -1.6 ± 0.9 vs. -0.9 ± 1.0, p = .002, respectively). Moreover, these patients had a significantly reduced rate of death or HF-hospitalization (4 vs. 29%, p = .001) and a significantly longer event-free-survival from Kaplan-Meier curves (p = .003). COX regression analysis showed that, among echocardiographic parameters, decrease in LA size was an independent predictor of clinical outcome (HR: 0.149, CI: 0.034-0.654, p = .012). CONCLUSIONS: The lack of decrease in LA size shortly after TAVR is associated with significantly higher rates of death and HF-hospitalization, as well as with impaired improvement in clinical status during long-term follow-up.