Atrial fibrillation before and after transcatheter aortic valve implantation: short- and long-term clinical implications.

BACKGROUND: Patients with atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI) have been associated with worse short-term outcomes compared with patients in sinus rhythm but data on long-term outcomes are limited. The aim of our study was to evaluate the association between AF and short- and long-term outcomes in patients undergoing TAVI. METHODS: We retrospectively evaluated patients undergoing TAVI between 2012 and 2022 in four tertiary centres. Two different analyses were conducted: (i) in-hospital and (ii) postdischarge analysis. First, we evaluated the association between preexisting AF and short-term outcomes according to VARC-3 criteria. Second, we analyzed the association between AF at discharge (defined as both preexisting and new-onset AF occurring after TAVI) and long-term outcomes at median follow-up of 3.2 years (i.e. all-cause death, hospitalization and major adverse cardiovascular events). RESULTS: A total of 759 patients were initially categorized according to the presence of preexisting AF (241 vs. 518 patients). The preexisting AF group had a higher occurrence of acute kidney injury [odds ratio (OR) 1.65; 95%confidence interval ( CI) 1.15-2.38] and major bleeding (OR 1.86, 95% CI 1.06-3.27). Subsequently, the population was categorized according to the presence of AF at discharge. At the adjusted Cox regression analysis, AF was independently associated with an increased risk of all-cause death and cardiovascular hospitalization [adjusted hazard ratio (aHR) 1.42, 95% CI 1.09-1.86], all-cause death and all-cause hospitalization (aHR 1.38, 95% CI 1.06-1.78) and all-cause hospitalization (aHR 1.59, 95% CI 1.14.2.22). CONCLUSIONS: In a real-world cohort of patients undergoing TAVI, the presence of AF (preexisting and new-onset) was independently associated with both short- and long-term adverse outcomes.

Effects of Ivabradine on Right Ventricular Systolic Function in Patients With Chronic Obstructive Pulmonary Disease and Cor Pulmonale.

Cor pulmonale is a clinical syndrome associated with pulmonary hypertension, frequently complicated by congestive heart failure, commonly caused by chronic obstructive pulmonary disease (COPD). Most patients with cor pulmonale have tachycardia. However, heart rate (HR) reduction represents a primary treatment goal to improve the survival and quality of life in these patients. Ivabradine can selectively slow HR at rest and during exercise. In this prospective study, we tested the hemodynamic effects, invasively determined using right-sided cardiac catheterization, of reducing HR with ivabradine. We selected 18 patients (13 men [72.2%], mean age 67 ± 10 years) with COPD and cor pulmonale, presenting with sinus tachycardia. All patients performed clinical evaluation, electrocardiogram, spirometry, echocardiogram, 6-minute walking distance, and right-sided cardiac catheterization within 1 month of enrollment. All tests were repeated after 6 months of ivabradine treatment (median assumed dose 11.9 mg/die). We noticed a significant decrease of HR (from 98 ± 7 to 77 ± 8 beats/min, p = 0.0001), with a concomitant reduction of the congestion index (from 25.9 ± 5.1 to 19.4 ± 5.7 mm Hg, p = 0.001), and the consequent improvement of the right ventricular systolic performance (right ventricular stroke volume augmented from 56.7 ± 7.9 to 75.2 ± 8.6 ml/beat, p = 0.0001). This allows an improvement in clinical status and exercise tolerance (Borg scale score decreased from 5.2 ± 1.4 to 4.1 ± 1.3, p = 0.01 and the 6-minute walking distance increased to 252 ± 65 to 377 ± 59 m, p = 0.001). In conclusion, HR reduction significantly improves hemodynamic and clinical status of patients with tachycardia affected by COPD and cor pulmonale.

The Importance of Mehran Score to Predict Acute Kidney Injury in Patients with TAVI: A Large Multicenter Cohort Study.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has developed as an alternative to surgery for symptomatic high-risk patients with aortic stenosis (AS). An important complication of TAVI is acute kidney injury. The purpose of the study was to investigate if the Mehran Score (MS) could be used to predict acute kidney injury (AKI) in TAVI patients. METHODS: This is a multicenter, retrospective, observational study including 1180 patients with severe AS. The MS comprised eight clinical and procedural variables: hypotension, congestive heart failure class, glomerular filtration rate, diabetes, age >75 years, anemia, need for intra-aortic balloon pump, and contrast agent volume use. We assessed the sensitivity and specificity of the MS in predicting AKI following TAVI, as well as the predictive value of MS with each AKI-related characteristic. RESULTS: Patients were categorized into four risk groups based on MS: low (≤5), moderate (6-10), high (11-15), and very high (≥16). Post-procedural AKI was observed in 139 patients (11.8%). MS classes had a higher risk of AKI in the multivariate analysis (HR 1.38, 95% CI, 1.43-1.63, p < 0.01). The best cutoff for MS to predict the onset of AKI was 13.0 (AUC, 0.62; 95% CI, 0.57-0.67), whereas the best cutoff for eGFR was 42.0 mL/min/1.73 m2 (AUC, 0.61; 95% CI, 0.56-0.67). CONCLUSIONS: MS was shown to be a predictor of AKI development in TAVI patients.

Low Levels of Vitamin D and Silent Myocardial Ischemia in Type 2 Diabetes: Clinical Correlations and Prognostic Significance.

Vitamin D deficiency has a pathogenetic and prognostic role in coronary artery disease and a key role in pain transmission. Diabetic patients have a higher risk of silent myocardial ischemia (SMI) due to diabetic neuropathy. We evaluated the correlation between SMI and Vitamin D serum levels in type 2 diabetic patients and assessed whether SMI patients had a worse survival rate than their symptomatic counterpart. We enrolled 253 patients admitted in our Cardiology Unit and compared them with 50 healthy volunteers. We created three sub-groups: symptomatic MI group (125, 32.4%); SMI group (78, 25.7%), and no-MI group (50, 41.9%). 25(OH)D levels (nmol/L) were lower in the SMI group (34.9 ± 5.8) compared to those in the symptomatic MI (49.6 ± 6.1; p = 0.01), no MI (53.1 ± 6.2; p = 0.001), and control groups (62.1 ± 6.7; p = 0.0001). 25(OH)D levels predicted SMI in diabetic patients, with an inverted odds ratio of 1.11 (p = 0.01). Symptomatic MI group survival was higher than the SMI one (6-year survival rate: 83 vs. 69%; p = 0.01). Diabetic patients with SMI had a higher mortality risk and showed lower 25(OH)D levels than the symptomatic group. This suggests the crucial role that vitamin D has in the pathogenesis of SMI.

Anthropometric parameters and radiation doses during percutaneous coronary procedures.

PURPOSE: Body size is a major determinant of patient's dose during percutaneous coronary interventions (PCI). Body mass index, body surface area (BSA), lean body mass and weight are commonly used estimates for body size. We aim to identify which of these measures and which procedural/clinical characteristics can better predict received dose. METHODS: Dose area product (DAP, Gycm2), fluoroscopy DAP rate (Gycm2/min), fluoroscopy DAP (Gycm2), cine-angiography DAP (Gycm2), Air Kerma (mGy) were selected as indices of patient radiation dose. Different clinical/procedural variables were analysed in multiple linear regression models with previously mentioned patient radiation dose parameters as end points. The best model for each of them was identified. RESULTS: Overall 6623 PCI were analysed, median fluoroscopy DAP rate was 35 [IQR 2.7,4.4] Gycm2, median total DAP was 62.7 [IQR 38.1,107] Gycm2. Among all anthropometric variables, BSA showed the best correlation with all radiation dose parameters considered. Every 1 m2 increment in BSA added 4.861 Gycm2/min (95% CI [4.656, 5.067]) to fluoroscopy DAP rate and 164 Gycm2 (95% CI [145.3, 182.8]) to total DAP. Height and female sex were significantly associated to a reduction in fluoroscopy DAP rate and total DAP. Coronary angioplasty, diabetes, basal creatinine and the number of treated vessels were associated to higher values. CONCLUSIONS: Main determinants of patient radiation dose are: BSA, female sex, height and number of treated vessels. In an era of increasing PCI complexity and obesity prevalence, these results can help clinicians tailoring X-ray administration to patient's size.

Impact of body mass index on the outcome of elderly patients treated with transcatheter aortic valve implantation.

Underweight or overweight patients with cardiovascular diseases are associated with different outcomes. However, the data on the relation between body mass index (BMI) and outcomes after transcatheter aortic valve implantation (TAVI) are not homogeneous. The aim of this study was to assess the role of low BMI on short and long-term mortality in real-world patients undergoing TAVI. We retrospectively included patients undergoing TAVI for severe aortic valve stenosis. Patients were classified into three BMI categories: underweight (< 20 kg/m2), normal weight (20-24.9 kg/m2) and overweight/obese (≥ 25 kg/m2). Our primary endpoint was long-term all-cause mortality. The secondary endpoint was 30-day all-cause mortality. A total of 794 patients were included [mean age 82.3 ± 5.3, 53% females]. After a median follow-up of 2.2 years, all-cause mortality was 18.1%. Patients in the lowest BMI group showed a higher mortality rate as compared to those with higher BMI values. At the multivariate Cox regression analysis, as compared to the normal BMI group, BMI < 20 kg/m2 was associated with long-term mortality independently of baseline risk factors and postprocedural adverse events (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.30-4.03] and HR 2.61, 95% CI 1.48-4.60, respectively). The highest BMI values were found to be protective for both short- and long-term mortality as compared to lower BMI values even after applying the same adjustments. In our cohort, BMI values under 20 kg/m2 were independent predictors of increased long-term mortality. Conversely, the highest BMI values were associated with lower mortality rates both at short- and long-term follow-up.

Red Cell Distribution Width and Patient Outcome in Cardiovascular Disease: A ''Real-World'' Analysis.

Red cell distribution width (RDW) has been shown to predict adverse outcomes in specific scenarios. We aimed to assess the association between RDW and all-cause death and a clinically relevant composite endpoint in a population with various clinical manifestations of cardiovascular diseases. We retrospectively analyzed 700 patients (median age 72.7 years [interquartile range, IQR, 62.6-80]) admitted to the Cardiology ward between January and November 2016. Patients were divided into tertiles according to baseline RDW values. After a median follow-up of 3.78 years (IQR 3.38-4.03), 153 (21.9%) patients died and 247 (35.3%) developed a composite endpoint (all-cause death, acute coronary syndromes, transient ischemic attack/stroke, and/or thromboembolic events). With multivariate Cox regression analysis, the highest RDW tertile was independently associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 2.73, 95% confidence interval [CI] 1.63-4.56) and of the composite endpoint (adjusted HR 2.23, 95% CI 1.53-3.24). RDW showed a good predictive ability for all-cause death (C-statistics: 0.741, 95% CI 0.694-0.788). In a real-world cohort of patients, we found that higher RDW values were independently associated with an increased risk of all-cause death and clinical adverse cardiovascular events thus proposing RDW as a prognostic marker in cardiovascular patients.

Effects of sildenafil on right ventricle remodelling in Portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is a clinical condition associated with end-stage liver disease, described by the coexistence of pulmonary arterial hypertension (PAH) and portal hypertension. In PoPH patients, there is a right ventricle (RV) remodeling to compensate for the increased resistance in the lung circulation. There are no studies on the effects of the PAH-targeted pharmacological treatment on the RV dimension and function. The present study summarizes our experience in patients with PoPH treated with sildenafil in a period of 6 years (from 2013 to 2019). We enrolled 64 consecutive patients identified as PoPH, all treated with sildenafil (57.6% in monotherapy; in the other cases in association with macitentan; in 19.0% with initial combination therapy). A hemodynamic invasive cardiopulmonary study was performed at baseline and after 6 months of sildenafil treatment. In our population we showed a significative improvement in RV performance, with a significant increase in RV stroke volume (+33%), RV ejection fraction (+31%) and RV stroke work index (+17.5%). We registered the reduction of the RV cavity dimension over time in all patients treated with sildenafil (RV end diastolic diameter decreased by 15% after 6 months of follow-up). Regarding diastolic function, we highlighted a very significant reduction in RV end-diastolic pressure (-50% concerning baseline). Sildenafil was effective both when used as monotherapy and in combination with macitentan. In conclusion, Sildenafil had a positive impact on RV systolic and diastolic function in patients with PoPH and was able to conditionate the reverse remodeling of the RV.

Percutaneous pericardiocentesis for pericardial effusion: predictors of mortality and outcomes.

Pericardial effusion can dangerously precipitate patient's hemodynamic stability and requires prompt intervention in case of tamponade. We investigated potential predictors of in-hospital mortality, a composite outcome of in-hospital mortality, pericardiocentesis-related complications, and the need for emergency cardiac surgery and all-cause mortality in patients undergoing percutaneous pericardiocentesis. This is an observational, retrospective, single-center study on patients undergoing percutaneous pericardiocentesis (2010-2019). We enrolled 81 consecutive patients. Median age was 71.4 years (interquartile range [IQR] 58.1-78.1 years) and 51 (63%) were male. Most of the pericardiocentesis were performed in an urgency setting (76.5%) for cardiac tamponade (77.8%). The most common etiology was idiopathic (33.3%) followed by neoplastic (22.2%). In-hospital mortality was 14.8% while mortality during follow-up (mean 17.1 months) was 44.4%. Only hemodynamic instability (i.e., cardiogenic shock, hypotension refractory to fluid challenge therapy and inotropes) was associated with in-hospital mortality at the univariate analysis (odds ratio [OR] 7.2; 95% confidence interval [CI] 1.76-29.4). Non-neoplastic/non-idiopathic etiology and hemodynamic instability were associated with the composite outcome of in-hospital mortality, need for emergency cardiac surgery, or pericardiocentesis-related complications (OR 5.75, 95% CI 1.65-20.01, and OR 5.81, 95% CI 2.11-15.97, respectively). Multivariate Cox regression analysis adjusted for possible confounding variables (age, coronary artery disease, and hemodynamic instability) showed that neoplastic etiology was independently associated with medium-term mortality (hazard ratio [HR] 4.05, 95% CI 1.45-11.36). In a real-world population treated with pericardiocentesis for pericardial effusion, in-hospital adverse outcomes and medium-term mortality are consistent, in particular for patients presenting with hemodynamic instability or neoplastic pericardial effusion.

Focal bilateral motor seizures precipitated by abrupt cessation of chronic lormetazepam abuse and amitriptyline overdose.

We report the case of an adult psychiatric patient who developed new-onset focal bilateral motor seizures (FBMS) in the context of a severe benzodiazepine withdrawal syndrome. The patient was forced to interrupt chronic lormetazepam abuse and overdosed on amitriptyline (800 mg in an oral solution) before the onset of seizures. Typical signs of amitriptyline intoxication such as sedation and anticholinergic effects were not observed. Video-EEG recordings revealed a stereotypical ictal motor pattern with asymmetric tonic posturing and bilateral clonic movements of the upper limbs, but there were no abnormalities identified by EEG. Seizures recurred multiple times per day but resolved simultaneously when withdrawal symptomatology subsided eight days after onset. Nonepileptic seizures (NES) were considered in the differential diagnosis because of the patient's psychiatric history including preserved awareness during the bilateral convulsions, the absence of postictal confusion, and normal EEG. The present case indicates that FBMS may occur during benzodiazepine withdrawal in patients who overdosed on amitriptyline. The diagnosis may be challenging as FBMS may mimic NES in the absence of abnormal neurophysiologic findings. This may be especially challenging in patients with an underlying psychiatric disease.

Effect on mortality of different routes of administration and loading dose of aspirin in patients with ST-segment elevation acute myocardial infarction treated with primary angioplasty.

BACKGROUND: Aspirin is the cornerstone of the anti-platelet therapy during the acute phase of ST-segment elevation myocardial infarction (STEMI), and it can be administrated orally or intravenously. The oral loading dose of aspirin is well characterized, whereas there are little data on the optimal intravenous (IV) loading dose. AIM: To confirm if the mortality of patients treated with a loading dose of IV aspirin was comparable to that of patients treated with the most usual aspirin per os. PATIENTS AND METHODS: We analyzed the overall mortality during hospitalization and at 1 year follow-up among 756 consecutive patients with STEMI. Four hundred seventy-eight (63.2%) patients received per os and 278 (36.8%) IV aspirin. We divided the 278 patients of the IV aspirin group into two subgroups, based on the median value of the dose of aspirin used as a load. RESULTS: The per os aspirin group took 234 ± 138 mg of aspirin per os at the first medical contact; the IV low-dose group 194 ± 87 mg, and the IV high-dose group 483 ± 194 mg of IV aspirin. No differences were observed in mortality rate after 1-year of follow-up. In-hospital mortality resulted significantly higher (9.3%) in the IV high-dose group respect to the IV low-dose one (5.0%) and per os aspirin group (6.0%) (P < 0.01 for both). CONCLUSION: In this retrospective study, high dose IV aspirin loading in STEMI increased intra-hospital mortality. Further study is necessary to define the optimal dose of intravenous aspirin in STEMI.

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer's Disease in Transgenic Mice at Different Ages.

Backgroud: Alzheimer disease is an age-related severe neurodegenerative pathology. The level of the third endogenous gas, hydrogen sulfide (H2S), is decreased in the brain of Alzheimer's disease (AD) patients compared with the brain of the age-matched normal individuals; also, plasma H2S levels are negatively correlated with the severity of AD. Recently, we have demonstrated that systemic H2S injections are neuroprotective in an early phase of preclinical AD. OBJECTIVES: This study focuses on the possible neuroprotection of a chronic treatment with an H2S donor and sulfurous water (rich of H2S) in a severe transgenic 3×Tg-AD mice model. METHOD: 3×Tg-AD mice at 2 different ages (6 and 12 months) were daily treated intraperitoneally with an H2S donor and sulfurous water (rich of H2S) for 3 months consecutively. We investigated the cognitive ability, brain morphological alterations, amyloid/tau cascade, excitotoxic, inflammatory and apoptotic responses. RESULTS: Three months of treatments with H2S significantly protected against impairment in learning and memory in a severe 3×Tg-AD mice model, at both ages studied, and reduced the size of Amyloid ß plaques with preservation of the morphological picture. This neuroprotection appeared mainly in the cortex and hippocampus, associated with reduction in activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in the phosphorylation of tau protein but also in the inflammatory and excitotoxic response. CONCLUSION: Our findings indicate that appropriate treatments with various sources of H2S, might represent an innovative approach to counteract early and severe AD progression in humans.

Percutaneous Endoscopic Transgastric Jejunostomy (PEG-J) Tube Placement for Levodopa-Carbidopa Intrajejunal Gel Therapy in the Interventional Radiology Suite: A Long-term Follow-up.

BACKGROUND: Percutaneous endoscopic gastrojejunostomy (PEG) and radiologically inserted gastrojejunostomy (RIG) are both safe and effective techniques for gastrojejunal tube placement. The authors compared these 2 procedures in patients with advanced Parkinson's disease (PD) who required the continuous intrajejunal delivery of a levodopa/carbidopa gel suspension (LCIG). METHODS: Outcomes were retrospectively collated from 30 PEG and 12 RIG procedures performed at 2 centers in patients with advanced PD for the delivery of LCIG. RESULTS: Baseline clinical characteristics, incidence of early severe adverse events, late major complications, dropout, and the mean time-lapse of tube replacements were comparable in the PEG and RIG groups. CONCLUSION: The current results suggest that, in patients with PD, the RIG technique is as safe and effective as the endoscopic procedure, and it can be considered a valid option for patients who require LCIG when the endoscopic procedure is not available or unfeasible.