Background: Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. Objective: To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Methods: Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Results: Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p,0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p,0.05) and a 47.52% (p,0.01) relative reduction in the infarct size, respectively. Conclusion: Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

Background Titin is a giant sarcomeric protein that plays a major role in determining passive myocardial stiffness. The shorter N2B isoform results in a higher passive myocardial stiffness than the longer N2BA isoform. We hypothesised that expression of the short N2B isoform would be increased in patients with aortic stenosis compared with healthy controls in response to pressure overload, in order to act as a modulator for the increased demand placed on the left ventricle during the early stages of the hypertrophic response. Methods Myocardial biopsies were obtained from the left ventricle of 19 patients undergoing aortic valve replacement for aortic stenosis who had no significant co-existing coronary artery disease. Left ventricular biopsies were also obtained from thirteen donor hearts for comparison. Results SDS-agarose gels revealed small N2B and large N2BA cardiac titin isoforms with a mean N2BA:N2B ratio that was significantly decreased in the 19 aortic stenotic patients compared with the 13 controls (0.66 ± 0.04 in the normal donor hearts versus 0.48 ± 0.03 in patients with aortic stenosis; p=0.02). However, total titin remained unchanged (0.28 ± 0.02 vs. 0.24 ± 0.02; p=0.29). Conclusion Expression of less N2BA and more N2B titin in response to pressure overload will result in the generation of higher passive tension upon stretch to a given sarcomere length and this might affect cardiac performance.

In the past few years, the dogma that the heart is a terminally differentiated organ has been challenged. Evidence from preclinical investigations emerged that there are cells, even in the heart itself, that may be able to restore impaired cardiac function after myocardial infarction. Although the exact mechanisms by which the infarcted heart can be repaired by stem cells are not yet fully defined, there is a new optimism among cardiologists that this treatment will prove successful in addressing the cause of heart failure after myocardial infarction-myocyte loss. Despite the promising preliminary data of human myocardial stem cell trials, scientists have also focused on the possibility of enhancing the underlying mechanisms of stem cell repair to gain healthier myocardial tissue. Attempts to induce neo-angiogenesis by transfecting stem cells with signaling factors (such as VEGF), to raise the number of endothelial progenitor cells with medical treatments (such as statins), to transfect stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and to enhance the healing process after myocardial infarction with the use of various forms of stimulating factors (G-CSF, SCF, GM-CSF) have been made with notable results. In this article, we summarize the evidence from preclinical and clinical myocardial stem cell studies that have addressed the possibility of enhancing the regenerative capacity of cells used after myocardial infarction.

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Background Infective endocarditis (IE) is a rare, but life-threatening complication of cardiac device implantation. Despite recent preventive strategies, and advances in antimicrobial and surgical treatment, morbidity and mortality rates are still high. Aims The objective of our study was to assess the epidemiological characteristics, temporal tends and mortality rate of cardiac device related IE (CDRIE) in our high-volume, tertiary referral center. Methods retrospective data collection was performed from January 1, 2006 to December 31, 2016. Thirty-day, 6-month and 1-year mortality was estimated, which were compared to left-sided native valve endocarditis (LSNIE). Patients administered between 2006 and 2010 and between 2011 and 2016 were compared to assess temporal trends. Results 465 cases of IE were administered, out of whom 54 patients had CDRIE (39 males [72%], mean age: 55.8 ±19 yrs; 4 VVI, 7 VDD, 7 VVI-ICD, 20 DDD, 5 DDD-ICD and 11 CRT devices; median time since first implantation: 1558 days [IQR: 470 days – 8.6 yrs]). The infection was caused by streptococci in 3 cases (5.5%), Staphylococci were the most prevalent infective agents (70%), S. aureus (SA) in 28 cases (52%, out of whom 10 were MRSA), coagulase negative Staphylococcus in 10 cases (18.5%), blood culture negative cases in 8 patients (15%), and in 5 cases other pathogens were responsible. 266 patients had LSNIE (201 males [75%], mean age: 54.4 ± 15.6 yrs). There was no difference between the two groups in age or in portion of males. Mortality rates were the same in CDRIE group compared to LSNIE group (30-day: 13% vs 13%, 6-month: 20% vs 25%, 1-year: 26% vs 29% and long-term: 44% vs 44%, ns resp.) Patients who died in the CDRIE group (n = 25) were older (64 yrs [IQR:59-71 yrs] vs 52 yrs [IQR: 27-69 yrs], p = 0.02), male sex was less common (52% vs 79%, p = 0.03), had lower ejection fraction (39.6 ±16.6% vs 54.6 ±14.5%, p < 0.001), had worse renal function (GFR: 46.3 ± 15.3 vs 60.2 ± 23.5 ml/min/1.73m2, p = 0.04), shorter time since first device implantation (2.1 yrs [IQR: 1.1-4.8 yrs] vs 6.7 yrs [4.1-12.9 yrs], p = 0.006), and CRT device implantation were more prevalent (32% vs 10%, p < 0.05). Patients admitted before 2011 (n = 22) did not differ from patients admitted after 2011 (n = 32) in terms of age, male gender, concomitant valve infection, pocket infection, or embolic event. The 30-day (0% vs 6%) and the 1-year mortality (18% vs 31%) were the same before and after 2011, but the 6-month mortality was better before 2011 (4.5% vs 31%, p = 0.01). CRT device implantation was more prevalent over time (5% vs 31%, p = 0.01), and SA infection became more frequent (36% vs 63%, p = 0.05) Conclusions During the last decade patients with CDRIE had a same survival as patients with LSNIE, every fourth patient died one year after the diagnosis. Almost three-quarter of the infections were caused by Staphylococci, and the portion of S. aureus infection increased over time.