1,720,999 research outputs found
Cardiovascular inhalation for targeted drug delivery in cardiac disease
No full textRecombinant proteins, cell, and gene therapies are collectively defined as biological drugs or biologics. These therapies have transformed the lives of millions of patients over the past decades, with the number of FDA-approved biologics increasing exponentially in recent years. However, out of approximately 700 biological therapies approved by the FDA in the last 20 years, less than 1% are indicated for cardiac pathologies. The application of biologics in cardiovascular disease has faced significant challenges, including short plasma half-life, the multifactorial complexity of cardiac disease, and the lack of efficient, non-invasive, and patient-friendly drug-delivery routes. This translational gap is particularly pressing given the immense socioeconomic burden of cardiovascular disease, which remains the leading cause of death globally and accounts for billions in annual healthcare costs and lost productivity. Inhalation-based drug delivery has recently emerged as a promising strategy for treating cardiovascular disease, with several proof-of-concept studies demonstrating its potential in heart failure, the most prevalent cardiac condition. This narrative review summarizes the latest experimental evidence in the novel field of Cardiovascular Inhalation, i.e., the lung-to-heart route for biologics. We discuss translational challenges, preclinical evidence, and future perspectives for bringing this innovative approach to clinical practice
Valore prognostico della presenza di disturbi della conduzione cardiaca nei pazienti affetti da amiloidosi AL
No full textPrognostic value of cardiac conduction delays in light-chain (AL) amyloidosis
Among the different types cardiac amyloidoses, light-chain (AL) amyloidosis has the worst prognostic outcome.
The mechanism of death is usually sudden cardiac death, due to tachyarrythmias, bradyarrythmias and/or electromechanical
dissociation. To evaluate the possible association between these arrhythmic events and conduction delays detectable on a standard 12 lead ECG, prevalence and prognostic impact of conduction disturbances were assessed in 337 consecutive AL patients at the time of diagnosis; median follow up was 402 days. The prevalence of conduction delays was significantly higher in patients with cardiac AL amyloidosis than in patients without cardiac involvement (41% vs 24% respectively, p<0.05). Analysis of different morphologic, diastolic and systolic parameters
(interventricular septum thickness, Doppler E/E’ ratio and mitral annulus longitudinal excursion or MAPSE) showed a worse echocardiographic presentation in cardiac AL patients with conduction delays. Furthermore, prognosis was markedly worse in patients with cardiac AL amyloidosis and intraventricular conduction delays
Valore prognostico della presenza di bassi voltaggi elettrocardiografici nei pazienti affetti da amiloidosi AL
No full textPrognostic value of electrocardiographic low voltages in patients affected by AL amyloidosis
AL amyloidosis is a systemic diseases characterized by extracellular deposition, in various tissues, of immunoglobulin
(Ig) light chain or a Ig light chain fragment synthesized by clonal bone marrow plasma cells. Cardiac involvement is not only frequent but it is also the most common cause of death. The 12-leads electrocardiogram (ECG) reflects the infiltrative nature of this disease with low voltages in the limb leads, pseudoinfarction patterns and abnormalities of conduction such as fascicular block or varying degree atrioventricular block. In particular the presence of low voltages was defined as QRS voltage amplitude ≤0.5 mV in all limb leads. Besides confirming the importance of a simple, affordable and non-invasive tool such as ECG for the diagnose of cardiac AL amyloidosis, aim of the present study was to assess the potential prognostic role of low ECG voltages.
We enrolled 126 consecutive never-treated subjects, in whom a first diagnosis of primary AL amyloidosis was concluded in 2009 at the Pavia Amyloidosis Center. The cohort was divided into two
groups depending on the presence (n=86) or the absence (n=40) of cardiac involvement and, along with the staging system proposed by the Mayo Clinic, into 3 stages with different prognosis: STAGE 1 (n=24), STAGE 2 (n=46), STAGE 3 (n=56). Standard 12-leads ECG and cardiac echo-colorDoppler data were evaluated at diagnosis, and prognosis was assessed after a median follow up of 500 days. When compared with patients without myocardial involvement, cardiac AL patients showed a higher prevalence of low voltages (61.6% vs 17.5%, p<0.0001). Kaplan-Meier survival analysis revealed a significantly higher mortality in patients with low voltages when compared with patient without low voltages (p=0.0356). The same trend wasn’t
confirmed in the group with cardiac involvement (p=0.613). This is most likely due to the fact that in this disease cardiac involvement is itself the most important and robust prognostic factor. The identification of low voltages allowed us to identify 2 subgroups with different prognosis inside STAGE 2. In detail 18-month survival was 55% for patients in STAGE 2 with low voltages as opposed to 88% for patients in the same stage but without low voltages. Beyond confirming the diagnostic value of the presence of low ECG voltages in patients affected by AL
amyloidosis, these data demonstrate the prognostic value of such a simple parameter as a factor that, together with the Mayo staging system, can help patient stratification at diagnosis
Intraoperative Evaluation of Right Ventricular Mechanics in a Pressure-Overload Swine Model
No full textObjectives: Assessment of right ventricular (RV) mechanical performance during open chest surgery is typically based on invasive methods and subjective evaluations. This study developed a porcine model of acute progressive RV pressure overload to evaluate hemodynamic changes and validate the 3D-video kinematic assessment of the Videocardiograph (VCG). Methods: Seven healthy Landrace pigs were instrumented under fluoroscopic guidance with Swan-Ganz and RV conductance catheters. Following a median sternotomy, pulmonary artery banding (PB) was performed in two stages to induce minimal (PBmin) and maximal (PBmax) pressure overload. In a proof-of-concept experiment, different PB steps were performed to record both videos for the VCG and invasive pressure-volume assessments (PV-loop). Additionally, these videos were subjectively evaluated by five consultant surgeons, similar to clinical routine. Results: PBmax significantly increased end-systolic pressure from baseline (21.17±3.31mmHg vs 39.85±7.82mmHg, p=0.001) and led to RV dilation, reduced ejection fraction (52.80±10.36% vs 33.99±9.88%, p=0.012), and decreased myocardial efficiency. In the proof-of-concept experiment, visual evaluations were highly variable among the cardiac surgeons, resulting in only a moderate reliability of their assessments (ICC=0.59 for RV-function; ICC=0.60 for filling status). VCG-derived epicardial z-axis displacements, systolic timing, diastolic velocity and volume demonstrated excellent relationships with PV-loop data. Conclusions: This study established a porcine model of progressive RV pressure overload with robust PV-loop assessment. VCG-derived epicardial kinematics reliably quantified RV mechanical activity and correlated with gold-standard hemodynamic measurements. This non-invasive, cost-effective method shows promise for early detection of acute RV dysfunction in the operating room and warrants further clinical investigation
Fibrillazione atriale e amiloidosi cardiaca AL: un connubio intrigante
No full textAtrial fibrillation and cardiac amylodosis: an intriguing combination
Primary systemic (AL) amyloidosis is a clonal plasma cell disorder in which the N-terminal fragments of monoclonal light chains form fibrils that accumulate in various organs, ultimately leading to organ dysfunction and death, that is very frequently caused associated with cardiac involvement. Since cardiac amyloidosis is characterized by severe left ventricular diastolic dysfunction, an impact on atrial structure and function is expected. This may lead to atrial dilatation and dysfunction, as well as to supraventricular
arrhythmias, eventually causing atrial fibrillation (AF), with all the well-known sequelae on cardiac pump function and on the risk of thromboembolism. In literature the estimated prevalence of atrial fibrillation ranges from 10% to 15%, that is somewhat lower than expected, when considering the extent of diastolic dysfunction (and of the consequent left atrial enlargement). Since little is known this aspect of cardiac AL amyloidosis, aim of the present study was to analyze the prevalence of atrial fibrillation in this clinical setting, in comparison with similar cardiac phenotypes of diastolic heart failure, namely hypertensive heart disease, heart failure and hypertrophic cardiomiopathy. Left atrial anteroposterior diameter was used as estimate of atrial size. We enrolled 161 consecutive never-treated subjects, in whom a first diagnosis of primary AL amyloidosis was concluded between 2008 and 2009. None of the AL patients without cardiac involvement showed AF. Despite higher left atrial diameters and volumes, only 14 patients presented with atrial fibrillation, with a prevalence (8.7%) that was lower than in other forms of diastolic heart failure (ranging from 13 to 19%) with the exception of hypertensive heart disease (3%). Moreover, left atrial enlargement was more evident in cardiac AL than in the other populations, and the presence of AF in cardiac AL patients was significantly associated with left atrial diameter, area and volume (p<0.05 for all comparisons). Therefore, in cardiac amyloidosis, AF prevalence is lower than expected when considering the extent of diastolic dysfunction (and of the consequent left atrial enlargement) and the comparison with other patients with diastolic heart failure. Amyloid deposit may be playing a major role in determining such a low prevalence. Further studies are needed to investigate these aspects
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
A Random Shuffle Method to Expand a Narrow Dataset and Overcome the Associated Challenges in a Clinical Study: A Heart Failure Cohort Example
Full text linkHeart failure (HF) affects at least 26 million people worldwide, so predicting adverse events in HF patients represents a major target of clinical data science. However, achieving large sample sizes sometimes represents a challenge due to difficulties in patient recruiting and long follow-up times, increasing the problem of missing data. To overcome the issue of a narrow dataset cardinality (in a clinical dataset, the cardinality is the number of patients in that dataset), population-enhancing algorithms are therefore crucial. The aim of this study was to design a random shuffle method to enhance the cardinality of an HF dataset while it is statistically legitimate, without the need of specific hypotheses and regression models. The cardinality enhancement was validated against an established random repeated-measures method with regard to the correctness in predicting clinical conditions and endpoints. In particular, machine learning and regression models were employed to highlight the benefits of the enhanced datasets. The proposed random shuffle method was able to enhance the HF dataset cardinality (711 patients before dataset preprocessing) circa 10 times and circa 21 times when followed by a random repeated-measures approach. We believe that the random shuffle method could be used in the cardiovascular field and in other data science problems when missing data and the narrow dataset cardinality represent an issue
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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