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Stem cell therapy is an emerging tool to treat a variety of conditions from cancer to musculoskeletal disorders to cardiac disease. Current FDA-approved stem cell therapies utilize cells from peripheral blood or bone marrow to treat patients who have disorders of the hematopoietic system; however clinical trials for utilizing stem cells to treat muscular skeletal disorders and cardiac disease are underway. Because stem cells self‐renew and differentiate in multiple lineage pathways, the general theory behind stem cell therapy is that damaged tissue can be repaired or regenerated and that trophic activity of stem cells can modulate other immune cells. While stem cell therapy has the potential to treat a variety of conditions due to its regenerative and proliferative activity, more study is needed to address ideal injection time, method of injection, distribution, and retention concerns. Imaging stem cells addresses these concerns and can provide more information overall about the fate of stem cells. Contrast agents are needed to increase the contrast and specificity of imaging stem cells. Nanoparticle‐based contrast agents are important tools for imaging because they offer high contrast and stable signal. Chapter 1 of this thesis provides a background on cell therapy and various imaging modalities. Chapter 2 details the design and synthesis of gadolinium-doped synthetic melanin nanoparticles which were used to label stem cells for photoacoustics and magnetic resonance imaging (MRI). Chapter 3 explores the mechanism of ultraviolet (UV)-induced synthetic melanin nanoparticle generation. Chapter 4 describes the design, synthesis, and application of an iron oxide PLGA-based nanoparticle used for ultrasound, photoacoustics, and magnetic particle imaging (MPI). Finally, Chapter 5 describes the synthesis and application of a nanoparticle for cancer treatment that shows an increase in photoacoustic intensity as drug is released. This nanoparticle was then used to treat tumors in mice and luminescence was used to monitor treatment response. Chapter 6 concludes with a perspective on the future of imaging cell therapy with possible directions.

Heart diseases (HDs) are the leading cause of morbidity and mortality worldwide. Despite remarkable clinical progress made, current therapies cannot restore the lost myocardium, and the correlation of genotype to phenotype of many HDs is poorly modeled. In the past two decades, with the rapid developments of human pluripotent stem cell (hPSC) biology and technology that allow the efficient preparation of cardiomyocytes from individual patients, tremendous efforts have been made for using hPSC-derived cardiomyocytes in preclinical and clinical cardiac therapy as well as in dissection of HD mechanisms to develop new methods for disease prediction and treatment. However, their applications have been hampered by several obstacles. Here, we discuss recent advances, remaining challenges, and the potential solutions to advance this field.

Aims Patients with non‐ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter‐defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM. Methods and results We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow‐up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74–1.00)], hypertension [HR 1.95; 95% CI (1.26–3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32–13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19–1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02–7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non‐sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin‐C (FLNC)] were associated with arrhythmic outcome in non‐pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high. Conclusions In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non‐)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter‐defibrillator implantation.

Myocardial external efficiency is the relation of mechanical energy generated by the left (or right) ventricle to the consumed chemical energy from aerobic metabolism. Efficiency can be calculated invasively, and, more importantly, noninvasively by using positron emission tomography, providing a single parameter by which to judge the adequacy of myocardial metabolism to generated mechanical output. This parameter has been found to be impaired in heart failure of myocardial or valvular etiology, and it changes in a characteristic manner with medical or interventional cardiac therapy. The authors discuss the concept, strengths, and limitations, known applications, and future perspectives of the use of myocardial efficiency.

OBJECTIVES The aims of this study were to evaluate taurine levels in English cocker spaniels with dilated cardiomyopathy and assess their survival time and natural progression of their disease. MATERIALS AND METHODS Retrospective comparison of English cocker spaniels with dilated cardiomyopathy phenotype with and without taurine deficiency at the cardiology department of a UK academic referral centre between 2008 and 2018. RESULTS Taurine plasma concentration was available in 16 English cocker spaniels with dilated cardiomyopathy phenotype; 13 of 16 had congestive heart failure and three of 16 did not. Taurine concentration was low (

Interventional radiology (IR) procedures tend to be complex, which delivers high radiation exposure to patient. In the present study, we measured the radiation exposure dose [Hp(3)] in the eye using a direct eye dosemeter placed next to the physician’s eye during procedures. Physicians wore a direct eye dosemeter just lateral to eyes and an additional direct eye dosemeter outside the radiation protective eyeglasses close to their eyes. Additionally, a neck glass badge was worn at the neck. Although we found a positive correlation between the left neck glass badge dose [Hp(0.07)] and the left eye lens dose [Hp(3)], the value of R2 of the regression equation were 0.62 and 0.71 (outside and inside). We thought that the exact eye lens dose might not be estimated from the neck glass badge. In conclusion, a correct evaluation of the lens dose [Hp(3)] using the direct eye dosemeter is recommended for tachyarrhythmia physicians.

Introduction: Cardiovascular diseases are accompanied by autonomic nervous system (ANS) imbalance which is characterized by decreased vagal tone. Preclinical and clinical studies have revealed that...

[EN]Cardiosphere-derived cells (CDCs) encapsulated within alginate-poly-L-lysine-alginate (APA) microcapsules present a promising treatment alternative for myocardial infarction. However, clinical translatability of encapsulated CDCs requires robust long-term preservation of microcapsule and cell stability, since cell culture at 37 degrees C for long periods prior to patient implantation involve high resource, space and manpower costs, sometimes unaffordable for clinical facilities. Cryopreservation in liquid nitrogen is a well-established procedure to easily store cells with good recovery rate, but its effects on encapsulated cells are understudied. In this work, we assess both the biological response of CDCs and the mechanical stability of microcapsules after long-term (i.e., 60 days) cryopreservation and compare them to encapsulated CDCs cultured at 37 degrees C. We investigate for the first time the effects of cryopreservation on stiffness and topographical features of microcapsules for cell therapy. Our results show that functionality of encapsulated CDCs is optimum during 7 days at 37 degrees C, while cryopreservation seems to better guarantee the stability of both CDCs and APA microcapsules properties during longer storage than 15 days. These results point out cryopreservation as a suitable technique for long-term storage of encapsulated cells to be translated from the bench to the clinic. This work has been supported by the European Union's H2020 Framework Program (H2020/2014-2020) and National Authorities through the Electronic Components and Systems for European Leadership Joint Undertaking (ECSEL JU) program under grant agreement Ecsel-78132-Position-II-2017-IA. The regional Government of Aragon provided L.P. studentship. This research was partially funded by Instituto de Salud Carlos III (PI20/00247) and Agencia Estatal de Investigacion (PID2019-107329RA-C22), cofunded by European Regional Development Fund "A way to make Europe."

Multimodal picture integration has been developed for improvements of visualization of interventional procedure in congenital and structural heart disease. 3D rotational angiography (3DRA) was used for that purpose in the past, and a 3D dataset was than imposed as an overlay for fluoroscopy. But 3DRA includes a 180° turn of the X-ray arm in order to generate a 3D dataset, including additional contrast application of 4–5 s, rapid pacing, and preparation of the catheterization lab.

A therapeutic application of electrical current to cardiac tissue for reviving the normal function (defibrillation, pacing) or for ablating pathological conduction pathways inevitably has to take into account the phenomenon of electroporation, the electric-field-induced rupture of sarcolemma that is usually evidenced by a drastic unselective increase in cell membrane permeability to small ions and large molecules. This chapter describes some aspects of this phenomenon in relation to cardiac therapy and research. Particularly, it provides evidences that (1) electroporation of the heart tissue can occur during clinically relevant intensities of the external electrical field and (2) electroporation can affect the outcome of defibrillation therapy, being both pro- and antiarrhythmic.

Cardiac arrhythmia is an abnormal electrical activity of the heart. It can be divided into rhythms with increased electrical activity (tachyarrhythmia) and those with reduced electrical activity (bradyarrhythmia). Ablation therapy has a role in tachyarrhythmia, but this role varies from being limited in inappropriate sinus tachycardia to being a class 1 indication in typical atrial flutter. A balanced approach in recommendation for ablation therapy for the management of tachyarrhythmias involves knowledge of the interplay between the risk, benefit, success rate, and alternatives with advances in mapping and ablation therapy.

Contains fulltext : 225390.pdf (Publisher’s version ) (Open Access) BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies. METHODS: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks. RESULTS: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12). CONCLUSIONS: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.).

Seizure disorders are associated with multisystem complications. Cardiovascular complications account for a significant proportion of morbidity and mortality in these patients. As such, particular attention must be paid to the incidence of cardiovascular complications especially in populations at increased risk. The background for cardiac dysfunction lies in the interplay of genetic/molecular, autonomic, and iatrogenic factors that contribute to its onset. The purpose of this review was to summarize the state of literature in the last decade with regard to cardiac complications of epileptic seizures in order to increase awareness of short- and long-term debilitating cardiac complications as well as facilitate informed clinical decision-making. Taken together, the evidence provided in this review suggests that cardiac dysfunction following seizures should not be viewed as a separate entity but as an important complication of epileptic seizures. Appropriate cardiac therapy should be instituted in the postictal medical management of epileptic seizures. In acute states, postictal cardiac troponinemia (elevated cTn) should be worked up. Longer-term, monitoring for the development of cardiac structural and functional abnormalities is prudent.

Introducao Ha varios seculos Portugal e Brasil tem uma longa tradicao de cooperacao. Na Medicina, sobretudo na area de Cardiologia, existe um longo historico de colaboracao entre as duas sociedades cientificas – a Sociedade Brasileira de Cardiologia e a Sociedade Portuguesa de Cardiologia – que se estende aos respetivos periodicos. Os Arquivos Brasileiros de Cardiologia ( Arq Bras Cardiol ), publicacao cientifica oficial da Sociedade Brasileira de Cardiologia, com fator de impacto de 1,679 em 2018 (JCR), e a revista [...]

We present the case of a patient with a subcutaneous implantable cardioverter-defibrillator (S-ICD) in situ. Device interrogation and reprogramming were unsuccessful due to a software mismatch between the device and programmer. The device manufacturer recommended magnet application to suspend antitachycardia therapy. Despite using this strategy, the S-ICD discharged multiple times. The S-ICD has unique perioperative considerations for the anesthesiologist. This case provides an example of the complexity of electrophysiologic devices in current use and the necessity of the anesthesia provider to stay up to date with evolving device management strategies.

Purpose of review Left ventricular assist devices (LVADs) have extended the life expectancy of patients with heart failure. The hemodynamic support afforded by LVADs in this population has also resulted in patients having prolonged ventricular arrhythmias. The purpose of this article is to review the mechanisms of ventricular arrhythmias in LVADs and the available management strategies. Recent findings Recent evidence suggests that prolonged ventricular arrhythmias may result in increased mortality in patients with LVADs. Summary Successful management of ventricular arrhythmias in patients with LVAD requires interdisciplinary collaboration between electrophysiology and heart failure specialists. Medical management, including changes to LVAD changes, heart failure medication management, and antiarrhythmics constitute the initial treatment for ventricular arrhythmias. Surgical or endocardial ablation are reasonable options if VAs are refractory.

This study investigated the association between left ventricular ejection fraction (LVEF) and the risk of ventricular arrhythmias (VA), heart transplantation, and death in cardiac sarcoidosis (CS). We identified 110 CS patients meeting 2014 Heart Rhythm Society (HRS) diagnostic criteria with baseline LVEF35% (n = 32) or ≥35% (n = 78). The primary end point was sustained VA or sudden cardiac death (SCD), and secondary end points included risk of heart transplantation, death, or a composite. Logistic regression determined risk factors for VA/SCD, and Cox proportional hazards regression analysis was performed for secondary end points. Receiver operating curve analysis determined the best discrimination point of LVEF for each end point; sensitivity analyses evaluated the effects of higher LVEF on each end point. Over a follow-up of 2.6 (range 1.0 to 5.8) years, 49 (44.5%) CS patients experienced VA/SCD, including 19 of 32 (59.4%) with LVEF35%, and 30 of 78 (38.5%) with LVEF ≥35%. After adjustment, LVEF35% was not significantly associated with an increased risk of VA/SCD compared with LVEF ≥35% (odds ratio 1.3, 95% confidence intervals 0.5 to 3.7). Although LVEF35% was associated with an increased risk of heart transplantation and death (28.1% vs 12.8%, p = 0.05), this was not significant after adjustment (hazard ratio 1.7, 95% confidence intervals 0.5 to 9.0, p = 0.53). In conclusion, patients with CS experience high rates of VA, SCD, and heart transplantation, even when LVEF is mildly impaired or normal. Patients with LVEF35% are at particularly elevated risk of VA/SCD. Our findings highlight the imperative to investigate arrhythmia risk in all patients with CS, even in the setting of an otherwise reassuring LVEF.

Biomaterials that are commonly used for the attenuation of adverse remodeling or as regenerative treatment for myocardial infarction (MI), often have the capacity to release drugs in a sustained manner, providing strength and stability to the infarcted area, or mimic the extracellular matrix. Retention and redistribution of the injected biomaterials is a factor often overlooked, but plays a significant role in the effectiveness of the treatment. Wash-out of therapeutics from the cardiac area can lead to unwanted side-effects and can therefore add insult to injury. Here, the authors seek a deeper understanding on the mechanisms that play an important role in the retention of injected therapeutics, being: materials, drugs, or a combination thereof. Several factors influencing the therapeutic quantity retained at the target site are discussed; being the timing of injection after MI, cardiac pulsation, and injectate properties such as volume, mechanical properties, and tissue affinity. The importance of understanding is highlighted and these different parameters are taken into. More insight in these parameters can lead to an increase in therapeutic effectiveness, in addition to examination of indirect off-target effects.

Why? The potential risks of sport for an ICD recipient include appropriate and inappropriate shocks, device damage and worsening of the underlying cardiopathy. These risks should be compared to the physical and psychological benefits of exercise. Where? Due to different medico-legal contexts and considering the results of recent studies, the new US guidelines are more permissive than the European guidelines regarding sport practice in ICD recipients. Who? The underlying context (structural or electrical cardiopathy, psychological impact) should be assessed before any decision is taken. What sport? The intensity and duration of the exercise, the environment, the type of sport (bodily contact sports or compromising the costoclavicular area) and the potential consequences for the patient or the spectators of a possible loss of consciousness must to be anticipated. How? The patient's information on the consequences of the ICD on his subsequent physical activity must be delivered before the device implantation. In addition, the type and programming of the ICD must be personalized according to the sport. When? The patient should wait at least 6 weeks after ICD implantation to return to leisure sport and after an exercise test has been performed. After a ventricular arrhythmia, the patient must wait 3 months before returning to sport.

Adverse hemodynamics of right ventricular (RV) pacing is known for years. Several studies have revealed that adverse outcomes of RV apical pacing are directly linked to cumulative percentage of ventricular pacing. Algorithms to minimize ventricular pacing are only effective if there is good atrioventricular (AV) conduction. A need for an alternate site for ventricular pacing is evident in patients with high presumed ventricular pacing burden. Most studied alternate site for ventricular pacing is ventricular septum (outflow tract septum and mid-septum). Conventionally septal position of the ventricular pacing lead is confirmed by fluoroscopic appearance of the lead and characteristics electrocardiographic (ECG) features. However, several recent studies have challenged these fluoroscopic and ECG features as to be inadequate. So, there is need for a systematic approach for septal positioning of the ventricular lead.

KEY POINTS A 25-year-old man with a medical history of propionic acidemia was brought to hospital after he collapsed while jogging. He was unresponsive, received immediate bystander cardiopulmonary resuscitation and was defibrillated by paramedics from an initial rhythm of ventricular fibrillation

The clinical translation of regenerative therapy for the diseased heart, whether in the form of cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses. Here, we report the development and application of a therapeutic epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium via a polymer-based reservoir connected to a subcutaneous port. In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the epicardial reservoir provided functional benefits in ejection fraction, fractional shortening and stroke work, compared to a single injection of cells and to no treatment. The pre-clinical use of the therapeutic epicardial reservoir as a research model may enable insights into regenerative cardiac therapy, and assist the development of experimental therapies towards clinical use.

An important aspect of cell therapy in the field of cardiac disease is safe and effective delivery of cells. Commonly used delivery strategies such as intramyocardial injection and intracoronary infusion both present with advantages and disadvantages. Therefore, alternative delivery routes are explored, such as retrograde coronary venous infusion (RCVI). Our aim is to evaluate safety and efficiency of RCVI by providing a complete overview of preclinical and clinical studies applying RCVI in a broad range of disease types and experimental models. Available data on technical and safety aspects of RCVI are incomplete and insufficient. Improvement of cardiac function is seen after cell delivery via RCVI. However, cell retention in the heart after RCVI appears inferior compared to intracoronary infusion and intramyocardial injection. Adequately powered confirmatory studies on retention rates and safety are needed to proceed with RCVI in the future. Electronic supplementary material The online version of this article (10.1007/s12265-018-9785-1) contains supplementary material, which is available to authorized users.