From cardiac repair to cardiac regeneration – ready to translate?

Cardiovascular disease is a major public health challenge in the western world. Mortality of acute events has improved, but more patients develop HF – a condition affecting up to 22 million people worldwide. Cell transplantation is the first therapy to attempt replacement of lost cardiomyocytes and vasculature to restore lost contractile function. Since the first reported functional repair after injection of autologous skeletal myoblasts into the injured heart in 1998, a variety of cell types have been proposed for transplantation in different stages of cardiovascular disease. Fifteen years of preclinical research and the rapid move into clinical studies have left us with promising results and a better understanding of cells as a potential clinical tool. Cell-based cardiac repair has been the first step, but cardiac regeneration remains the more ambitious goal. Promising new cell types and the rapidly evolving concept of adult stem and progenitor cell fate may enable us to move towards regenerating viable and functional myocardium. Meeting a multidisciplinary consensus will be required to translate these findings into safe and applicable clinical tools.     

In-hospital cardiac arrest: what happens to the false arrests?

OBJECTIVE: To investigate the events surrounding false cardiac arrest calls and subsequent outcome in patients who were the subjects of such calls. METHODS: A retrospective review of the cardiac arrest audit database pertaining to all false cardiac arrest calls logged by the hospital telephone switchboard at a London Teaching Hospital over a 22-month period. RESULTS: There were 59 false cardiac arrest calls. Of these 30 calls were immediately rescinded and 29 calls were erroneous. An abnormality of heart rhythm was the commonest cause for an erroneous call. Other important causes included epileptic seizure and hypovolaemia secondary to blood loss (whether due to medical or surgical causes). Three patients who were the subject of a rescinded call and 4 patients who were the subject of an erroneous call died in hospital without going home. Life table analysis revealed that for every 10 false arrests, eight patients were alive at 24 h, six patients were alive at 6 weeks, four patients were alive at 6 months and three patients were alive at 1 year. CONCLUSIONS: There is a need for a wider appreciation of the significance of false cardiac arrest calls.     

How to optimize in vivo gene transfer to cardiac myocytes: mechanical or pharmacological procedures?

An efficient gene delivery system is a prerequisite for myocardial gene therapy. Among the various procedures studied so far, catheter-based percutaneous gene delivery to the myocardium through the coronary vessels seems the most relevant to routine clinical practice; however, the optimal conditions remain to be determined. We selectively infused adenoviral vectors encoding luciferase (1 x 10(9) PFU) or beta-galactosidase (1 x 10(10) PFU) into coronary arteries of adult rabbits in various experimental conditions. Coronary artery occlusion for 30 sec, during and after adenovirus delivery, was required to observe luciferase activity in the target area of the circumflex artery (4.0 +/- 1.0 x 10(5) vs. 1.1 +/- 0.2 x 10(4) RLU/mg with and without coronary occlusion, respectively, p < 0.01, and 1.0 +/- 0.1 x 10(3) RLU/mg using nonselective infusion). When adenoviruses were delivered using high-pressure infusion (82 +/- 12 vs. 415 +/- 25 mmHg before and during infusion, respectively, p < 0.01), luciferase activity increased to 8.5 +/- 2.5 x 10(5) RLU/mg (p < 0.05 vs coronary occlusion alone). Coronary venous sinus occlusion with saline buffer retroinfusion starting before and during anterograde adenovirus delivery resulted in a further 4.7-fold increase in luciferase activity (4.4 +/- 0.8 x 10(6) RLU/mg, p < 0.01) with 5-25% blue-stained myocytes in the target area, compared with 0-5% with the other procedures. Histamine or VEGF-A(165) pretreatment, used to increase vascular permeability, slightly increased gene transfer efficiency (8.5 +/- 2.0 x 10(5) and 9.0 +/- 2.5 x 10(5) RLU/mg respectively, p < 0.05 vs. coronary occlusion alone). We conclude that catheter-mediated adenoviral gene transfer to cardiac myocytes through coronary vessels can be a very efficient procedure for myocardial gene therapy, particularly when the vector residence time and perfusion pressure in the vessels are increased.     

Cardiogenic shock and asphyxial cardiac arrest due to glutaric aciduria type Ⅱ

<正>Lipid storage myopathy(LSM) is a manifestation of lipid dysmetabolism, presenting with lipid accumulation in muscles. The mechanism includes defects in intracellular triglyceride catabolism, transport of long-chain fatty acids and carnitine, or fatty acid β-oxidation.^[1] Among LSMs, the most common type is multiple acyl-coenzyme A dehydrogenase deficiency(MADD),     

High-sensitivity troponin T and C-reactive protein to identify patients without cardiac structural and functional abnormalities as assessed by cardiac CT and SPECT imaging: can biomarkers predict cardiac health?

While high-sensitivity troponin-T (hsTnT) and C-reactive protein (hsCRP) are associated with structural heart disease, we thought to determine whether biomarkers can predict which heart is healthy based on multimodality imaging. Patients from the emergency department with acute chest pain suggestive of acute coronary syndrome undergoing contrast enhanced cardiac CT and stress single photon emission computed tomography (SPECT) myocardial perfusion imaging were included. HsTnT and hsCRP were assessed at time of CT. Imaging data were assessed for coronary atherosclerosis, left ventricular hypertrophy/dysfunction and myocardial perfusion abnormalities. Patients were stratified into those with or without any cardiac findings, who were considered as cardiac healthy. For biomarkers, low cut-off corresponding to good specificity and high cut-off corresponding to good sensitivity for cardiac health were derived. Among 117 patients (52 years, 55 % male), 42 (36 %) were cardiac healthy based on cardiac CT and SPECT imaging. These patients had significantly lower hsTnT and hsCRP levels as compared to those with functional or structural abnormalities (3.58 vs. 5.63 ng/L, p = 0.002; 0.82 vs. 1.93 mg/L, p = 0.0005; respectively). Patients with both low hsTnT (<3.00 ng/L) and hsCRP (<0.45 mg/L) had a probability of 85 % for being cardiac healthy. In contrast, patients with high hsTnT (>7.00 ng/L) and hsCRP (>2.00 mg/L) had 8 % probability for being cardiac healthy. Discriminative capacity of a dual-biomarker strategy was significantly improved as compared to hsTnT or hsCRP alone or to Framingham Risk score (AUC: 0.781 vs. 0.691; vs. 0.678; vs. 0.649; all p ≤ 0.02, respectively). A dual-biomarker strategy of hsTnT and hsCRP is highly discriminative for patients with normal cardiac structure and function and provides incremental value beyond the Framingham risk score.     

Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?

Introduction

Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis.

Methods

We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), of the regulator of the acute-phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity.

Results

The ex vivo production of TNF-α and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity.

Conclusion

Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-α and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti-inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL-6 is associated with a higher risk for postoperative pulmonary dysfunction.     

Deciphering cardiac involvement in systemic inflammatory diseases: noninvasive tissue characterisation using cardiac magnetic resonance is key to improved patients’ care

Introduction: Cardiac involvement in systemic inflammatory diseases (SID) has a major impact on patients’ morbidity and mortality, yet the pathways to its recognition and management remain poorly established.

Areas covered: Overall clinical management in SID patients is primarily guided by systemic symptoms. Cardiovascular disease goes largely undetected, as it evolves through years of a protracted and subclinical course. Despite the increased awareness and insights into the mechanistic role of the inflammatory pathways, clinical management of cardiac involvement continues to rely on diagnostic means, which are frequently insensitive, invasive and rely on radiation exposure. Advanced tissue characterisation with cardiovascular magnetic resonance (CMR) offers an accurate, non-invasive and radiation-free diagnostic method with obvious advantages: it is able to inform on a range of cardiovascular pathophysiology, as well as support safe serial examinations, informing on the disease presence, progress and response to treatment.

Expert commentary: We summarise the recent advances in non-invasive imaging, and bridge the novel insights into pathophysiology with future posibilities in diagnosis and manangement of SID patients. We propose an interdisciplinary framework to screening of cardiac involvement in SID using an indepth phenotyping of evolution of cardiovascular disease, to decipher the opportunities to improve patients’ cardiac care.     

Is the public equipped to act in out of hospital cardiac emergencies?

Methods: A cross sectional telephone survey, which contained sections regarding participant demographics, cardiopulmonary resuscitation (CPR) training, knowledge of CPR, and the emergency contact number and potential barriers to performing chest compressions and mouth to mouth.

Results: A total of 1489 people completed the questionnaire. Only 11% of the population had recently (<12 months) trained in CPR. When presented with a cardiac arrest scenario most participants stated that they would telephone 000. Significantly more respondents believed that they would give mouth to mouth to a family member compared with a stranger. A bleeding victim and fear of not having the skills were the most common barriers that reduced the participants perceived willingness to perform chest compressions and mouth to mouth.

Conclusion: This study suggests that a low percentage of the public is currently trained in CPR and also that they are unprepared to act in a cardiac emergency.

     

In-hospital cardiac arrest: Is outcome related to the time of arrest?

BACKGROUND: Whether outcome from in-hospital cardiopulmonary resuscitation (CPR) is poorer when it occurs during the night remains controversial. This study examined the relationship between CPR during the various hospital shifts and survival to discharge. METHODS: CPR attempts occurring in a tertiary hospital with a dedicated, certified resuscitation team were recorded prospectively (Utstein template guidelines) over 24 months. Medical records and patient characteristics were retrieved from patient admission files. RESULTS: Included were 174 in-hospital cardiac arrests; 43%, 32% and 25% in morning evening and night shifts, respectively. Shift populations were comparable in demographic and treatment related variables. Asystole (p < 0.01) and unwitnessed arrests (p = 0.05) were more common during the night. Survival to discharge was poorer following night shift CPR than following morning and evening shift CPR (p = 0.04). When asystole (being synonymous with death) was excluded from the analysis, the odds of survival to discharge was not higher for witnessed compared to unwitnessed arrest but was 4.9 times higher if the cardiac arrest did not occur during the night shift (p = 0.05, logistic regression). The relative risk of eventual in-hospital death for patients with return of spontaneous circulation (ROSC) following night shift resuscitation was 1.9 that of those with ROSC following morning or evening resuscitation (Cox regression). CONCLUSIONS: Although unwitnessed arrest is more prevalent during night shift, resuscitation during this shift is associated with poorer outcomes independently of witnessed status. Further research is required into the causes for the increased mortality observed after night shift resuscitation.