Wearable Cardioverter Defibrillator Shortens the Lengths of Stay in Patients with Left Ventricular Dysfunction after Myocardial Infarction: A Single-Centre Real-World Experience.

The wearable cardioverter defibrillator (WCD) has been proven to be effective in preventing sudden cardiac death (SCD) in patients soon after acute myocardial infarction (AMI) and left ventricular ejection fraction (LVEF) ≤35%. The aim of this study was to assess whether a WCD may shorten the length of an initial hospital stay (total length, days in the intensive care unit (ICU) and in the acute cardiac care unit (ACCU)) among these patients. This was a single-centre, retrospective observational study of patients referred for the management of SCD risk post-AMI and LVEF ≤35%, in a tertiary care hospital. The clinical characteristics and length of index hospitalization of the group of patients discharged, with or without WCD, were compared. A propensity score analysis was performed, then weighted regression models were conducted. A total of 101 patients in the WCD group and 29 in the control group were enrolled in the analysis. In the weighted regression models, WCD significantly reduced the days spent in ACCU (p < 0.001). WCD patients had significantly fewer days spent in ACCU (5.5 ± 2.6 vs. 8.4 ± 12.8 days, p < 0.001) and shorter hospitalizations (10.2 ± 5.7 vs. 13.4 ± 17.6 days, p = 0.005), compared with the control group. It was concluded that the WCD appears to reduce the total length of hospitalization and lengths of stay in ACCU for patients post-AMI and with left ventricular dysfunction.

[Atrial tachycardia degenerating into atrial fibrillation during recurrence of ischemic stroke: prolonged ECG monitoring in appropriately selected patients with embolic stroke of undetermined source]. / Tachicardia atriale che degenera in fibrillazione atriale durante recidiva di ictus ischemico: utilità diagnostica del monitoraggio ECG prolungato in pazienti con ictus embolico ad eziologia indeterminata adeguatamente selezionati.

The search for silent atrial tachyarrhythmias remains one of the cornerstones in patients suffering from embolic stroke of undetermined source. We report the case of a 76-year-old female patient suffering from recurrence of ischemic stroke, adequately selected based on the presence of predictors of atrial fibrillation (AF), to perform prolonged ECG monitoring. This recording allowed to document long-lasting AF triggered by atrial tachycardia. It was also possible to demonstrate a direct correlation between AF and new cerebral stroke.

Catheter Ablation of Well Tolerated Ventricular Tachycardia in Patients With Structural Heart Disease and Without Automatic Defibrillator Implantation: Long Term Follow-up.

The occurrence of a sustained monomorphic ventricular tachycardias (SMVT) in patients with underlying structural heart disease (SHD) is considered related to poor prognosis. The purpose of our work was to evaluate if these patients could benefit from radiofrequency (RF) ablation, and the defibrillator (ICD) implantation could be deferred during follow-up. We reviewed consecutive patients with well-tolerated SMVT, SHD and left ventricular ejection fraction over 30%. These patients were treated by RF ablation and were discharged without ICD. The primary outcome was a composite of all-cause death and recurrence of SMVT; the secondary outcome was death from all causes. Sixty-two patients were selected. After a median follow-up of 38.8 months, the primary outcome occurred in 24 (38.7%) and the secondary in 11 (17.7%) patients. The annual mortality rate was 4.3% and no patient died from sudden death. RF ablation as a first-choice therapy seems to represent an effective and beneficial therapeutic approach.

Exploiting Focused Ultrasound to Aid Intranasal Drug Delivery for Brain Therapy.

Novel effective therapeutic strategies are needed to treat brain neurodegenerative diseases and to improve the quality of life of patients affected by Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral sclerosis (ALS) as well as other brain conditions. At present no effective treatment options are available; current therapeutics for neurodegenerative diseases (NDs) improve cognitive symptoms only transiently and in a minor number of patients. Further, most of the amyloid-based phase III clinical trials recently failed in AD, in spite of promising preclinical and phase I-II clinical trials, further pinpointing the need for a better knowledge of the early mechanisms of disease as well as of more effective routes of drug administration. In fact, beyond common pathological events and molecular substrates, each of these diseases preferentially affect defined subpopulations of neurons in specific neuronal circuits (selective neuronal vulnerability), leading to the typical age-related clinical profile. In this perspective, key to successful drug discovery is a robust and reproducible biological validation of potential new molecular targets together with a concomitant set up of protocols/tools for efficient and targeted brain delivery to a specific area of interest. Here we propose and discuss Focused UltraSound aided drug administration as a specific and novel technical approach to achieve optimal concentration of the drug at the target area of interest. We will focus on drug delivery to the brain through the nasal route coupled to FUS as a promising approach to achieve neuroprotection and rescue of cognitive decline in several NDs.

Ultrasound-Based Method for the Identification of Novel MicroRNA Biomarkers in Prostate Cancer.

The detection of circulating microRNA (miRNA)-based biomarkers represents an innovative, non-invasive method for the early detection of cancer. However, the low concentration of miRNAs released in body fluids and the difficult identification of the tumor site have limited their clinical use as effective cancer biomarkers. To evaluate if ultrasound treatment could amplify the release of extracellular cancer biomarkers, we treated a panel of prostate cancer (PCa) cell lines with an ultrasound-based prototype and profiled the release of miRNAs in the extracellular space, with the aim of identifying novel miRNA-based biomarkers that could be used for PCa diagnosis and the monitoring of tumor evolution. We provide evidence that US-mediated sonoporation amplifies the release of miRNAs from both androgen-dependent (AD) and -independent (AI) PCa cells. We identified four PCa-related miRNAs, whose levels in LNCaP and DU145 supernatants were significantly increased following ultrasound treatment: mir-629-5p, mir-374-5p, mir-194-5p, and let-7d-5p. We further analyzed a publicly available dataset of PCa, showing that the serum expression of these novel miRNAs was upregulated in PCa patients compared to controls, thus confirming their clinical relevance. Our findings highlight the potential of using ultrasound to identify novel cell-free miRNAs released from cancer cells, with the aim of developing new biomarkers with diagnostic and predictive value.

Clinical management of electrical storm: a current overview.

The number of patients affected by electrical storm has been continuously increasing in emergency departments. Patients are often affected by multiple comorbidities requiring multidisciplinary interventions to achieve a clinical stability. Careful reprogramming of cardiac devices, correction of electrolyte imbalance, knowledge of underlying heart disease and antiarrhythmic drugs in the acute phase play a crucial role. The aim of this review is to provide a comprehensive overview of pharmacological treatment, latest transcatheter ablation techniques and advanced management of patients with electrical storm.

Role of cardiac imaging in patients undergoing catheter ablation of ventricular tachycardia.

Ventricular tachycardia is a major health issue in patients with structural heart disease (SHD). Implantable cardioverter defibrillator (ICD) therapy has significantly reduced the risk of sudden cardiac death (SCD) in such patients, but on the other hand, it has led to frequent ICD shocks as an emerging problem, being associated with poor quality of life, frequent hospitalizations and increased mortality. Myocardial scar plays a central role in the genesis and maintenance of re-entrant arrhythmias, as the coexistence of surviving myocardial fibres within fibrotic tissue leads to the formation of slow conduction pathways and to a dispersion of activation and refractoriness that constitutes the milieu for ventricular tachycardia circuits. Catheter ablation has repeatedly proven to be well tolerated and highly effective in treating VT and in the last two decades has benefited from continuous efforts to determine ventricular tachycardia mechanisms by integration with a wide range of invasive and noninvasive imaging techniques such as intracardiac echocardiography, cardiac magnetic resonance, multidetector computed tomography and nuclear imaging. Cardiovascular imaging has become a fundamental aid in planning and guiding catheter ablation procedures by integrating structural and electrophysiological information, enabling the ventricular tachycardia arrhythmogenic substrate to be characterized and effective ablation targets to be identified with increasing precision, and allowing the development of new ablation strategies with improved outcomes. In this review, we provide an overview of the role of cardiac imaging in patients undergoing catheter ablation of ventricular tachycardia.

Low-intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial-to-mesenchymal transition of colorectal cancer cells.

Ultrasound (US) offers potentially important opportunities from a therapeutic point of view. Thus, the study of the biological effects of US on cancer cells is important to understand the consequences of these changes on the malignant phenotype. This study aimed to investigate the effects of low-intensity ultrasound (LIPUS) on the phenotype of colorectal cancer cell lines. Cell proliferation was evaluated by viability test and by evaluation of pERK expression, while cell motility using the scratch test. Cell differentiation was evaluated assessing alkaline phosphatase activity. Epithelial mesenchymal transition was assessed by analyzing the expression of Vimentin and E-Cadherin. Release and uptake of extracellular vesicles (EVs) were evaluated by flow cytometry. LIPUS effects on the organization of cytoskeleton were analyzed by confocal microscopy and by evaluation of Rho GTPase expression. No alterations in vitality and clonogenicity were observed when the intermediate (0.4 MPa) and the lowest (0.035 MPa) acoustic intensities were administered while the treatment with high intensity (1 MPa) induced a reduction of both cell viability and clonogenicity in both cell lines in a frequency-dependent manner. LIPUS promoted the differentiation of colon cancer cells, affected epithelial-to-mesenchymal transition, promoted the closure of a wound as well as increased the release of EVs compared with untreated cells. LIPUS-induced increase in cell motility was likely due to a Rho GTPase-dependent mechanism. Overall, the results obtained warrant further studies on the potential combined effect of LIPUS with differentiating agents and on their potential use in a clinical setting.

Nationwide survey on the current practice of ventricular tachycardia ablation.

METHODS: We performed a nationwide survey on the current practice of ventricular tachycardia catheter ablation in Italy during the year 2016. RESULTS: Among 145 operators participating in the survey, 58 (40.0%) did not perform any ventricular tachycardia ablation in 2016. Among those performing ventricular tachycardia ablation, 9 operators (6.2%) performed only right ventricular endocardial catheter ablation, 52 (35.9%) performed endocardial catheter ablation both in the right and left ventricle (LV) and 26 (17.9%) performed both endocardial and epicardial LV catheter ablations. Seventy operators (89.7%) among the 78 performing LV and epicardial ablations treated patients with ischemic cardiomyopathy; ablations in the setting of other causes were less frequently performed. The following were considered as minimum requirements for ventricular tachycardia ablation: presence of a three-dimensional mapping system (120 operators, 82.8%), ICU in the hospital (118 operators, 81.4%), operator's training in high volume centers (93 operators, 64.1%). Twenty-eight operators (19.3%) performed catheter ablation in patients with electrical storm only after hemodynamic stabilization, 41 operators (28.3%) also during the acute phase and 9 operators (6.2%) never performed catheter ablation in electrical storm patients; the remaining 67 operators did not perform ventricular tachycardia ablation at all, or performed ablations only in the right ventricle. CONCLUSION: The present survey provides a snapshot of the current invasive treatment of ventricular tachycardia by catheter ablation. The procedure, especially in the setting of ischemic cardiomyopathy, is performed nationwide. Complex cases, including those with electrical storm, should be managed within a preestablished integrated network of regional referral centers able to transfer patients as soon as possible.

Focused Ultrasound Effects on Osteosarcoma Cell Lines.

MRI guided Focused Ultrasound (MRgFUS) has shown to be effective therapeutic modality for non-invasive clinical interventions in ablating of uterine fibroids, in bone metastasis palliative treatments, and in breast, liver, and prostate cancer ablation. MRgFUS combines high intensity focused ultrasound (HIFU) with MRI images for treatment planning and real time thermometry monitoring, thus enabling non-invasive ablation of tumor tissue. Although in the literature there are several studies on the Ultrasound (US) effects on cell in culture, there is no systematic evidence of the biological effect of Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) treatment on osteosarcoma cells, especially in lower dose regions, where tissues receive sub-lethal acoustic power. The effect of MRgFUS treatment at different levels of acoustic intensity (15.5-49 W/cm2) was investigated on Mg-63 and Saos-2 cell lines to evaluate the impact of the dissipation of acoustic energy delivered outside the focal area, in terms of cell viability and osteogenic differentiation at 24 h, 7 days, and 14 days after treatment. Results suggested that the attenuation of FUS acoustic intensities from the focal area (higher intensities) to the "far field" (lower intensities) zones might determine different osteosarcoma cell responses, which range from decrease of cell proliferation rates (from 49 W/cm2 to 38.9 W/cm2) to the selection of a subpopulation of heterogeneous and immature living cells (from 31.1 W/cm2 to 15.5 W/cm2), which can clearly preserve bone tumor cells.

[Premature ventricular beats: are they always benign? Diagnostic and therapeutic aspects]. / Extrasistolia ventricolare: è sempre benigna? Aspetti diagnostici e terapeutici.

Premature ventricular complexes (PVCs) are usually benign, and commonly only severely symptomatic patients are treated. In the literature, frequent PVCs have been reported to cause ventricular dysfunction, which may improve after PVC treatment. PVCs can also worsen the prognosis in patients with structural heart disease. Catheter PVC ablation is often the treatment of choice considering the high success rates. Ventricular dysfunction due to frequent PVCs is not always easy to identify as patients can be asymptomatic and the interpretation of imaging tests may be challenging in the presence of frequent PVCs. Treatment of patients with mild ventricular dysfunction is still a matter of debate.

Ultrasound affects minimal inhibitory concentration of ampicillin against methicillin resistant Staphylococcus aureus USA300.

Antimicrobial resistance is one of the most serious global public health problems. Therefore, novel strategies are needed to counteract bacterial resistance development. The aim of the present study was to enhance the activity of antibiotics to bacteria by using ultrasound. Ultrasound reduced the dosage of ampicillin required to impair bacterial viability.

Thorax Percutaneous Approach for Epicardial Ventricular Ablation in a Patient with Electrical Storm.

Subxiphoid puncture is considered the standard approach for epicardial ablation of ventricular arrhythmia, but in some cases this access is impracticable due to the patient's anatomy. We describe the case of a patient with electrical storm and abnormal subdiaphragmatic anatomy that precluded the usual subxiphoid approach. In this patient the pericardial space was gained through a direct thorax puncture at the fifth intercostals space close to the mammary line. The tools and technique utilized in this case were similar to what is usually used for traditional subxiphoid puncture. The thorax percutaneous puncture was successfully carried out without complication.

A Nonfluoroscopic Technique for Coronary Arteries Three-Dimensional Mapping during Epicardial Ventricular Tachycardia Ablation.

When performing epicardial ablation of ventricular tachycardia (VT), caution must be taken not to damage the coronary arteries. We report a case in which a new, nonfluoroscopic technique for incorporating an accurate, real-time reconstruction of the main coronary vessels into a three-dimensional electroanatomic map was used for epicardial VT ablation.

Cardiac device therapy in patients with left ventricular dysfunction and heart failure: 'real-world' data on long-term outcomes (mortality, hospitalizations, days alive and out of hospital).

BACKGROUND: The impact on long-term outcomes of implantable cardioverter defibrillators (ICDs) and biventricular defibrillators for cardiac resynchronization (CRT-D) devices in 'real world' patients with heart failure (HF) needs to be assessed in terms of clinical effectiveness. METHODS AND RESULTS: A registry including consecutive HF patients who underwent a first implant of an ICD (891 patients) or a CRT-D device (709 patients) in 2006-2010 was followed (median 1487 days and 1516 days, respectively), collecting administrative data on survival, all-cause hospitalizations, cardiovascular or HF hospitalizations, and days alive and out of hospital (DAOH). Survival free from death/cardiac transplant was 61.9% and 63.8% at 5 years for ICD and CRT-D patients, respectively. Associated comorbidities (Charlson Comorbidity Index) had a significant impact on death/cardiac transplant, as well as on hospitalizations. The median values of DAOH% were 97.4% for ICD and 97.7% for CRT-D patients, but data were highly skewed, with the lower quartile of DAOH% values including values ranging between 0% and 52.8% for ICD and between 0% and 56.1% for CRT-D patients. Charlson Comorbidity Index was a very strong predictor of DAOH%. CONCLUSIONS: Patients who were implanted in 'real world' clinical practice with an ICD or a CRT-D device have, on average, a relatively favourable outcome, with a survival of around 62-64% at 5 years, but with an important burden of hospitalizations. Comorbidities, as evaluated by means of the Charlson Comorbidity Index, have a significant impact on outcomes in terms of mortality/heart transplant, hospitalizations and days spent alive and out of hospital.

Combining therapeutic hypothermia and emergent coronary angiography in out-of-hospital cardiac arrest survivors: Optimal post-arrest care for the best patient.

BACKGROUND: Aggressive post-resuscitation care, in particular combining mild therapeutic hypothermia (MTH) with early coronary angiography (CAG) and percutaneous coronary intervention (PCI), may improve prognosis after out-of-hospital cardiac arrest (OHCA). OBJECTIVES: The study aims to assess the value of immediate CAG or PCI in comatose survivors after OHCA treated with MTH and their association with outcomes. METHODS: Observational, prospective analysis of all comatose, resuscitated patients treated with MTH at a tertiary centre and undergoing CAG or PCI ≤6 hours after OHCA, or non-invasively managed. Primary outcomes were 30-day and 1-year survival. RESULTS: From March 2004-December 2012, 141 (51%) out of 278 comatose patients after cardiac OHCA were treated with MTH (median age: 64.5 (interquartile range 55-73) years, males: 67%, first shockable rhythm: 70%, witnessed OHCA: 94%, interval OHCA-resuscitation ≤20 min: 81%). Ninety-seven patients (69%) underwent early CAG, and 45 (32%) of them PCI. Patients undergoing CAG or PCI had a more favourable risk profile than subjects non-invasively managed. PCI treated patients had more bleedings, but no stent thrombosis occurred. Thirty-day and one-year unadjusted total mortality rates were 50% and 72% for non-invasively managed patients, 26% and 38.7% for patients submitted only to CAG and 32% and 36.6% for patients treated with PCI (p=0.0435 for early death, and p<0.0001 for one-year mortality, respectively). However, a propensity-matched score analysis did not confirm the survival advantage of invasive management (p=0.093). At multivariable analysis, clinical and OHCA-related variables as well as CAG, but not PCI, were associated with outcomes. CONCLUSIONS: Comatose patients cooled after OHCA and submitted to emergency CAG or PCI are a favourable outcome population that receives optimal post-arrest care.

Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide.

Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half-life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half-life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo. Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. HSA-NMU displayed long-lasting, potent anorectic, and glucose-normalizing activity. When compared side by side with a previously described PEG conjugate, HSA-NMU proved superior on a molar basis. Collectively, our results reinforce the notion that NMU-based therapeutics are promising candidates for the treatment of obesity and diabetes.