Global longitudinal strain to determine optimal timing for surgery in primary mitral regurgitation: A systematic review.

BACKGROUND: Primary mitral regurgitation (PMR) results in adverse remodeling changes and left ventricular (LV) dysfunction. Assessing LV function has prognostic value in predicting morbidity and mortality. Indications for surgery include parameters such as LV ejection fraction (LVEF) and systolic dimensions. Current guidelines are limited in identifying patients at optimal time for surgery. Impaired postoperative LVEF indicates poor prognostic outcomes and subsequent heart failure. Global longitudinal strain (GLS) via speckle tracking echocardiography (STE) presents as a promising parameter to detect subclinical dysfunction in asymptomatic patients. METHODS: Following PRISMA guidelines, a literature search was conducted with Cochrane Library, PudMed, SCOPUS, and Web of Science. Key MeSH terms included "mitral regurgitation," "mitral valve insufficiency," "global longitudinal strain," "deformation," "LV-GLS," and "GLS." Inclusion criteria included (1) patients with severe PMR, (2) mixed population of symptomatic and asymptomatic patients, (3) standardized methods in assessing LV systolic function using 2D-STE, (4) valve repair or replacement surgery, and (5) patient outcomes measured after surgery. Search returned 234 papers, 12 of which met the inclusion criteria and were subsequently reviewed. RESULTS: Baseline GLS is an independent predictor of postoperative outcomes, ranging from -17.9 to -21.7% GLS. A significant negative correlation was observed between preoperative GLS and postoperative LVEF. Impaired baseline GLS was associated with higher mortality rates. Better long-term survival rates were seen in patients who underwent early surgery. CONCLUSION: GLS shows sensitivity in predicting long-term postoperative outcomes. Further analysis is required to determine preoperative GLS threshold to identify asymptomatic patients at the optimal time for mitral valve surgery.

Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide.

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

Identification of cardiac myosin-binding protein C as a candidate biomarker of myocardial infarction by proteomics analysis.

Acute myocardial infarction (AMI) is a common cause of death for which effective treatments are available provided that diagnosis is rapid. The current diagnostic gold standards are circulating cardiac troponins I and T. However, their slow release delays diagnosis, and their persistence limits their utility in the identification of reinfarction. The aim was to identify candidate biomarkers of AMI. Isolated mouse hearts were perfused with oxygenated protein-free buffer, and coronary effluent was collected after ischemia or during matched normoxic perfusion. Effluents were analyzed using proteomics approaches based on one- or two-dimensional initial separation. Of the 459 proteins identified after ischemia with one-dimensional separation, 320 were not detected in the control coronary effluent. Among these were all classic existing biomarkers of AMI. We also identified the cardiac isoform of myosin-binding protein C in its full-length form and as a 40-kDa degradation product. This protein was not detected in the other murine organs examined, increased markedly with even trivial myocardial infarction, and could be detected in the plasma after myocardial infarction in vivo, a profile compatible with a biomarker of AMI. Two-dimensional fluorescence DIGE of ischemic and control coronary effluents identified more than 200 asymmetric spots verified by swapping dyes. Once again existing biomarkers of injury were confirmed as well as posttranslational modifications of antioxidant proteins such as peroxiredoxins. Perfusing hearts with protein-free buffers provides a platform of graded ischemic injury that allows detailed analysis of protein release and identification of candidate cardiac biomarkers like myosin-binding protein C.

Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress?

Sarcolemmal Na(+)/H(+) exchanger (NHE) activity, which is provided by the NHE isoform 1 (NHE1), has been implicated in ischemia/reperfusion-induced myocardial injury in animal models and humans, on the basis of studies with pharmacological NHE1 inhibitors. We generated a transgenic (TG) mouse model with cardiac-specific over-expression of NHE1 to determine whether this would be sufficient to increase myocardial susceptibility to ischemia/reperfusion-induced injury. TG mouse hearts exhibited increased sarcolemmal NHE activity and normal morphology and function. Surprisingly, they also showed reduced susceptibility to ischemia/reperfusion-induced injury, as reflected by improved functional recovery and smaller infarcts. Such protection was sustained in the presence of NHE1 inhibition with zoniporide, indicating a mechanism that is independent of sarcolemmal NHE activity. Immunoblot analysis revealed accumulation of immature NHE1 protein as well as marked upregulation of both cytoprotective (78/94 kDa glucose-regulated proteins, calreticulin, protein disulfide isomerase) and pro-apoptotic (C/EBP homologous protein) components of the endoplasmic reticulum (ER) stress response in TG myocardium. With increasing age, NHE1 TG mice exhibited increased myocyte apoptosis, developed left ventricular contractile dysfunction, underwent cardiac remodelling and died prematurely. Our findings indicate that: (1) Cardiac-specific NHE1 over-expression induces the ER stress response in mouse myocardium, which may afford protection against ischemia/reperfusion-induced injury despite increased NHE activity; (2) Ageing NHE1 TG mice exhibit myocyte apoptosis, cardiac remodelling and failure, likely as a result of sustained ER stress; (3) The pluripotent effects of the ER stress response may confound studies that are based on the chronic over-expression of complex proteins in myocardium.

Coronary collaterals remain recruitable after percutaneous intervention.

BACKGROUND: Rapid loss of collateral support has been reported after percutaneous coronary intervention (PCI), leaving the myocardium susceptible to subsequent infarction. However, well-developed collaterals have been found in normal hearts, suggesting that collaterals exist even in the absence of an ischemic stimulus. We assessed the plasticity and determinants of collateral supply after PCI. METHODS AND RESULTS: Collateral flow index (CFI) was calculated in 60 patients as (P(w)-P(v))/(P(a)-P(v)) by measurement of aortic (P(a)), central venous (P(v)), and coronary wedge (P(w)) pressures. CFI was reassessed during transient balloon occlusion 5 minutes and 24 hours after PCI in the first 29 patients and at 6 months in the subsequent 25 patients. We also evaluated the relationship between collateral supply, lesion characteristics, and circulating hemopoietic cells numbers before and after successful PCI. CFI at baseline was 0.23+/-0.10, with no change 5 minutes and 1 day later (0.21+/-0.12, P=0.62; and 0.22+/-0.11, P=0.96, respectively). At 6 months, CFI was 0.14+/-0.07 or 63+/-27% of the baseline value (P<0.001). CFI was proportional to severity of the coronary lesion at baseline (r=0.63, P<0.0001) but not 6 months after PCI (r=-0.04, P=0.87). The number of circulating CD133+ and CD34+ cells was associated with CFI 6 months after PCI (CD133, r=0.59, P=0.035; CD34, r=0.63, P=0.037). CONCLUSIONS: Coronary collateral flow remains undiminished for at least 24 hours after successful PCI. Functional collateral support subsequently declines but does not regress completely.

Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men.

OBJECTIVES: The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs). METHODS AND RESULTS: 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 microU/mL; P = 0.02). South Asians had lower FMD (6.9 versus 8.5%; P = 0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P = 0.03), mean SNP response (9.5+/-0.6 versus 11.6+/-0.6; P = 0.02), EPC number (0.046+/-0.005% versus 0.085+/-0.009%; P = < 0.001), and CFU ability (CFU 4.29+/-1.57 versus 18.86+/-4.00; P = 0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number. CONCLUSIONS: Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk.

Varying susceptibility to myocardial infarction among C57BL/6 mice of different genetic background.

Genetically manipulated mouse lines are invaluable to investigate the effects of a single gene on sensitivity to ischemia. When choosing appropriate controls, we were concerned that intrinsic, strain-independent but colony-dependent differences may influence the susceptibility to ischemia. We, therefore, compared the infarct:risk volume ratio (I:R%) after 30-min global ischemia in Langendorff-perfused hearts from outbred C57BL/6 mice with that in wild-type mice derived from heterozygote x heterozygote crosses of two different in-house C57BL/6 mouse lines with targeted disruption of an MKK3 or MAPKAPK2 allele. Despite similar hemodynamic characteristics, I:R% in outbred C57BL/6 hearts was significantlysmaller (40.8 +/- 2.8%) than in C57BL/6 MAPKAPK2 wild types (65.8 +/- 4.5%, P = 0.0003) and significantly larger than in C57BL/6 MKK3 wild types (23.7 +/- 2.9%, P = 0.002). Therefore, inherent colony substrain-dependent differences appear to influence the susceptibility to infarction in response to global ischemia, underscoring the importance of using colony-matched wild-type controls in murine studies of myocardial ischemia.