Cardiac Pacing Therapy in Developing Countries

Leon Ptaszek

Delivery of hydrogels to the heart is a potential strategy for reducing scar burden following myocardial infarction. The gelatin methacryloyl (GelMA) bioadhesive hydrogel could address limitations of previously reported hydrogels. The elasticity of GelMA was adjusted to match that of mouse myocardium. GelMA was then applied to the epicardial surface of mouse hearts at the time of experimental myocardial infarction (MI). GelMA was delivered as a liquid precursor and was polymerized into a solid scaffold in situ using visible-spectrum light. Left ventricular scar burden and survival were measured three weeks after MI. GelMA application was performed safely and was associated with significantly improved post-MI survival. GelMA application was also associated with reduced scar burden and improved left ventricular function.

 

Predictors of Progression to Heart Failure after Breast Cancer

Kerryn Reding

Progression to heart failure (HF) after breast cancer is a substantial cause of morbidity and mortality. One feature of this is progression to Stage C HF, of which a predominant symptom is reduced exercise capacity. Diminished exercise capacity, manifesting as shortness of breath, in those receiving treatment for breast cancer is prevalent (occurs in 1/3 of women), contributes to reduced quality of life, threatens to offset recent improvement in cancer related survival, and has an unclear relationship to body composition due to limitations of prior research study designs. To date, research into the etiology of reduced exercise capacity among BCa survivors has focused on the role of cardiac changes, e.g., left ventricular (LV) dysfunction, because of the known association between anthracycline chemotherapy and reductions in LV ejection fraction. The role of body fat has mostly been examined via body mass index (BMI), but results inconsistently predict diminished exercise capacity and LV ejection fractions (LVEF) declines. This may be due to the inability of BMI to distinguish body fat depots that do or do not associate with decreased exercise capacity. Recently in 2 studies, our team showed that central adiposity (specifically, elevated intraperitoneal [IP] fat) and fat accumulating within SM (i.e., intermuscular fat [IMF]) were associated with progression to HF, including demonstration of associations with reduced exercise capacity, fatigue, LV dysfunction, and HF symptoms (including dyspnea and exertional limitations) among women treated for breast cancer. Interestingly, in these studies, we did not observe associations between these events and BMI or subcutaneous (SQ) fat. These observations raise the possibility that excess fat accumulation within IMF and IP depots (which incidentally are modifiable) contribute to diminished exercise capacity experienced by women treated for breast cancer.

 

Platelet activation dynamics determine thrombus size and structure at arterial but not venous shear

Chris Jones

Platelet response to activating stimuli and pharmaceutical agents varies greatly within the normal population. The majority of data on platelet function comes from endpoint assays, yet platelets function in a dynamic environment and the kinetics of their response is likely to be just as physiologically relevant. To evaluate this, we have developed bespoke real-time flow cytometry assays and an analysis package that enables the measurement of the rate of platelet activation over time. The kinetics of platelet activation we assessed in 143 fasted, healthy, aspirin free donors. A recall of 12 individuals from the initial cohort was used to assess the effect of platelet response kinetics on thrombus formation and structure. The rate of platelet activation varied considerably within the normal population but did not correlate with maximal platelet activation, demonstrating that platelet rate is a separate and novel metric to describe platelet reactivity. The relative rate of platelet response between agonists was strongly correlated, suggesting a central control mechanism regulates the rate of platelet response to all agonists. Furthermore, platelet response kinetics correspond to thrombus size and structure, where faster responders form larger, more densely packed thrombi at arterial, but crucially not venous shear. We have demonstrated that the rate of platelet activation is an important metric in stratifying individual platelet responses. This provides a novel focus for the design and development of anti-platelet therapy, targeting high shear thrombosis without exacerbating bleeding at low shear.

 

Improvement of the outcome in child patients with dilated cardiomyopathy

Etsuko Tsuda

Background: The treatment of heart failure has changed with the use of angiotensin converting enzyme inhibitors (ACEIs) and beta-blockers since the middle of the 1990’s. However, the outcome in infantile dilated cardiomyopathy (DCM) when treated with them remains poorly understood. Methods: We reviewed the medical records of infants with DCM within 24 months old in our hospital between 1979 and 2012, and compared the outcome in the later group (1997-2012) with that in the early group (1979-1996). The survival and cardiac event (CE) free survival rates were calculated by the Kaplan–Meier method. Results: There were 20 patients in the early group and 24 patients in the later group. The median left ventricular fractional shortening at the onset of disease in the early and later groups were 11% (range 4-17) and 12% (range 4-25), respectively. In the later group, ACEIs and beta-blockers were administered in 22 and 21 patients, respectively. An usual low dose induction of carvedilol therapy (0.01-0.02mg/kg/day) sometimes worsened the heart failure in 9 patients (43%) after the successful initial conventional treatment for acute heart failure. Nineteen patients died and 25 survived. The CEs were as follows: heart transplantation 4, mitral valvuloplasty 1, Batista operation with mitral valve replacement 1, and cardiac resynchronization therapy in the late period 1. The 20-year survival rate in the early and later groups were 5% (95%CI 0.7-28) and 100%, respectively (p<0.001). The 2-year CE free survival rate in the early and later groups were 5% (95%CI 0.7-28) and 83% (95%CI 59-91), respectively (p<0.001). Conclusions: The outcome in patients with infantile DCM has significantly improved with careful acute and chronic treatments using ACEs and beta-blockers since the 2000’s. Adopting a long-term supportive treatment during a period of low ventricular function and the use of beta-blockers corresponding to each patient’s condition were key to survival.

 

Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10 years in the CLARICOR randomised

Naqash Sethi

BACKGROUND Antibiotics were believed to be able to reduce the risk of new harmful events in patients with coronary heart disease. In contrast, conflicting results have suggested that antibiotics might increase the risk of cardiovascular events and mortality. No previous systematic review using Cochrane methodology has been conducted on this topic.
OBJECTIVES
We assessed the benefits and harms of antibiotics versus placebo or no intervention for the secondary prevention of coronary heart disease in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, SCI‐EXPANDED, and BIOSIS in December 2019 in order to identify relevant trials.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data. Our primary outcomes were all‐cause mortality and quality of life. We also assessed four secondary outcomes. We extracted data at maximum and 24±6 months follow‐up. We assessed the risks of systematic errors using Cochrane ‘Risk of bias’ tool. The certainty of the body of evidence was assessed by GRADE.
MAIN RESULTS
We included 38 trials randomising a total of 26,638 participants (mean age 61.6 years). Trials assessing the effects of macrolides (28 trials; 22,059 participants) contributed with the vast majority of the data.
Meta‐analyses at maximum follow‐up showed that antibiotics seemed to increase the risk of all‐cause mortality (RR 1.06; 95% CI 0.99 to 1.13; P = 0.07; I2 = 0%; 25,774 participants; high certainty of evidence), stroke (RR 1.14; 95% CI 1.00 to 1.29; P = 0.04; I2 = 0%; 14,774 participants; high certainty of evidence), and probably also cardiovascular mortality (RR 1.11; 95% CI 0.98 to 1.25; P = 0.11; I2= 0%; 4674 participants; moderate certainty of evidence).
Meta‐analyses at 24±6 months follow‐up showed that antibiotics increased the risk of all‐cause mortality (RR 1.25; 95% CI 1.06 to 1.48; P = 0.007; I2 = 0%; 9517 participants; high certainty of evidence), cardiovascular mortality (RR 1.50; 95% CI 1.17 to 1.91; P = 0.001; I2 = 0%; 9044 participants; high certainty of evidence), and probably also sudden cardiac death (RR 1.77; 95% CI 1.28 to 2.44; P = 0.0005; I2 = 0%; 4520 participants; moderate certainty of evidence).
AUTHORS’ CONCLUSIONS
Our present review indicates that macrolides for secondary prevention of coronary heart disease seem harmful. Current evidence does, therefore, not support the clinical use of macrolides for the secondary prevention of coronary heart disease.