SCINTIGRAPHY AFTER VARIOUS METHODS OF MYOCARDIAL REVASCULARIZATION

Background. This article presents a comprehensive assessment of the perfusion-functional state of the LV myocardium after direct and indirect revascularization methods at various times after surgery to evaluate the complex relationship between myocardial viability and the method of revascularization. Methods. The study included 214 patients who underwent myocardial revascularization in various ways. Gated-SPECT was performed before the operation, as well as 1 month, 6 months, 1 year, and 2 or more years after the operation. Results. The groups of patients after CABG and CABG+YurLeon had differences in SRS indicators two years after surgery: 6.58±5.37 (after CABG) and 1,57±1,12 (CABG+YurLeon)(p<0.05).The most significant changes in systolic thickening (WT) occurred in segments with an accumulation of 26-40%: 1.8±1.14 (CABG), 0.51±0.35 (CABG+YurLeon), 2.6±1.19 (PCI); and in segments 41-50%: 1.23±1.10 (CABG), 0.14±0.11 (CABG+YurLeon), 2.1±0.8 (PCI) (p<0.05).In the long-term period after revascularization, the total percentage of LV myocardial segments with “functional-perfusion mismatch” stood at: 11.08±10.69% of segments (CABG), 1.26±1.2% (CABG+YurLeon), 18.44±8.70% (PCI) (p<0.05). Conclusions. Comprehensive diagnostics of patients before surgery, including gated-SPECT, allow medical professionals to more effectively choose the method of revascularization and predict the nearest and separated results. Coronary bypass surgery together with the YurLeon technique of indirect myocardial revascularization in patients with severe diffuse lesions of the coronary artery shows more effective results than other methods of surgically treating IHD.

Scintigraphy after Various Methods of Myocardial Revascularization

This article presents a comprehensive assessment of the perfusion-functional state of the LV myocardium after direct and indirect revascularization methods at various times after surgery to evaluate the complex relationship between myocardial viability and the method of revascularization. The research shows a significant advantage to using the YurLeon method of inducing extracardial revascularization of the myocardium in patients with diffuse coronary lesions. Aim. Comparative dynamic of scintigraphic indicators with various methods of revascularization. Materials and Methods.The study included 214 patients who underwent myocardial revascularization in various ways. Gated-SPECT was performed before the operation, as well as 1 month, 6 months, 1 year, and 2 or more years after the operation. Results.The groups of patients after CABG and CABG+YurLeon had differences in SRS indicators one year after surgery: 6.58±7.37 (after CABG) and 1.01±1.49 (CABG+YurLeon)(p<0.05).The most significant changes in systolic thickening (WT) occurred in segments with an accumulation of 26-40%: 1.78±1.84 (CABG), 0.51±0.85 (CABG+YurLeon), 2.6±1.19(PCI); and in segments 41-50%: 1.23±1.10 (CABG), 0.14±0.39 (CABG+YurLeon), 2.1±0.8 (PCI) (p<0.05).In the long-term period after revascularization, the total percentage of LV myocardial segments with "functional-perfusion mismatch" stood at: 11.08±11.69% of segments (CABG), 1.26±2.7% (CABG+YurLeon), 18.44±8.70% (PCI) (p<0.05). Conclusion. Comprehensive diagnostics of patients before surgery, including gated-SPECT, allow medical professionals to more effectively choose the method of revascularization and predict the nearest and separated results. Coronary bypass surgery together with the YurLeon technique of indirect myocardial revascularization in patients with severe diffuse lesions of the coronary artery shows more effective results than other methods of surgically treating IHD.

Systolic thickening fraction of inerventricular septum as a predictor of superresponse to cardiac resyncronisation therapy - concept of a helical ventriсular band

Aim: to assess morpho-functional properties of left ventricle (LV) in patients with superresponse (SR) to CRT using the helical ventriсular band concept (HVB).Materials and methods: 56 patients were examined (mean age 54.0±9.9 years) at baseline and during follow-up visit: 48.8±25.6 months. Patients were divided into groups: I group (n=34) with decrease of LV end-systolic volume (ESV) ≥30% (superresponders) and II group (n=22) - decrease of LV ESV ˂30% (nonsuperresponders).Results: apical loop descendens segment (DS) and ascendens segment (AS) of HVB were evaluated according to the concept of F. Torrent-Guasp et al. According to the logistic regression mechanical interventricular delay (MID) (OR 1.072, 95% CI 1.017-1.131; p=0.01) and systolic thickening fraction (STF) of interventricular septum (IVS) DS (OR 0.944, 95% CI 0.895 - 0.995; p = 0.033) had an independent relationship with CRT SR. According to the ROC analysis the sensitivity and specificity of this model were 72.7% and 66.7% (AUC=0.769; р=0.001). AS STF of IVS was higher in SR (22.5 [0.0;40.0]% и 0.0 [0.0;25.0]%; р=0.005). The survival rate in group I was 85.1%, in group II was 63.6% (Log-Rank test p=0.019).Conclusion: SR is associated with a higher AS STF of IVS, higher MID, also with a higher survival rate.

P5389Limited regenerative potential of the neonatal porcine heart after myocardial infarction

Background Neonatal murine hearts possess -for a brief period after birth- a robust capacity for spontaneous myocardial regeneration following cardiac injury. Whether hearts of neonatal large mammals possess similar regenerative potential is a matter of active investigation. Recently, two studies reported that 1-day-old and 2-day-old neonatal pigs exhibit a significant cardiac regenerative response post-myocardial infarction (MI), characterized by minimal cardiac fibrosis and spontaneous recovery of left ventricular (LV) function; this regenerative capacity is purportedly lost after the first two days of life. Purpose We sought to evaluate the regenerative potential of neonatal porcine hearts after MI. Methods Twenty-one neonatal farm pigs were randomly assigned to undergo MI by permanent ligation of the left anterior descending artery on postnatal day 1 (P1) or postnatal day 3 (P3). Infarcted P1 and P3 pigs were euthanized either at 1 week or at 7 weeks post-MI. Hearts explanted at 1 week post-MI underwent fluorescent immunohistochemistry for Ki67 and alpha-sarcomeric actinin to quantify myocyte cell cycle re-entry. Transthoracic echocardiography was performed at 7 weeks post-MI to quantify fractional shortening and systolic thickening of the anterior (infarcted) LV wall and the posterior (non-infarcted) LV wall. Hearts explanted at 7 weeks post-MI underwent staining with triphenyl-tetrazolium chloride and Masson's Trichrome to quantify infarct size, infarct circumference and infarct transmurality. Results Fourteen animals successfully completed the protocol. Infarct size (P1: 9.5±2.2% vs P3: 8.9±3.6% of LV, p=0.797), infarct circumference (P1: 33.8±7.1% vs P3: 29.8±10.6% of LV, p=0.566) and infarct transmurality (P1: 38.1±4.3% vs P3: 40.4±13.7% of anterior wall, p=0.764) were comparable in P1 and P3 animals at 7 weeks post-MI. LV fractional shortening (an index of global LV systolic function) was similar in P1 and P3 animals at 7 weeks post-MI (P1: 25.5±2.9% vs P3: 23.7±4.5%, p=0.662). Furthermore, systolic thickening in the anterior (infarcted) LV wall was depressed to a similar degree in P1 and P3 animals (P1: 31.8±5.3% vs P3: 32.3±8.5%, p=0.914) compared to systolic thickening in the posterior (non-infarcted) wall (P1: 72.5±9.0% vs P3: 69.0±11.4%, p=0.666) at 7 weeks post-MI. Myocyte cell cycle re-entry in the infarct border zone was increased in P1 animals compared to P3 animals (P1: 4.5±1.3 vs P3: 2.3±0.6 per field of view, p=0.045) at 1 week post-MI. Conclusions In contrast to recently-published reports, we did not observe a robust cardiac regenerative response in neonatal porcine hearts post-MI. Hearts of both 1-day-old and 3-day-old neonatal pigs exhibited substantial scarring and significant hypokinesia of the infarcted myocardium post-MI. Additional research is warranted to assess the cardiac regenerative potential of neonatal large mammals. Acknowledgement/Funding Co-financed by Greece and the European Union - European Social Fund

Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial

ObjectiveTo assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).MethodsThe Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Participants were enrolled at 3 US medical centers between January and August 2016 and followed for 12 months. An independent Data and Safety Monitoring Board provided safety oversight. Cardiac function and structure were assessed by MRI, and analyzed by a blinded core laboratory. Skeletal muscle function was assessed by performance of the upper limb (PUL).ResultsTwenty-five eligible patients (mean age 17.8 years; 68% wheelchair-dependent) were randomized to CAP-1002 (n = 13) or control (n = 12). Incidence of treatment-emergent adverse events was similar between groups. Compared to baseline, MRI at 12 months revealed significant scar size reduction and improvement in inferior wall systolic thickening in CAP-1002 but not control patients. Mid-distal PUL improved at 12 months in 8 of 9 lower functioning CAP-1002 patients, and no controls (p = 0.007).ConclusionsIntracoronary CAP-1002 in DMD appears safe and demonstrates signals of efficacy on both cardiac and upper limb function for up to 12 months. Thus, future clinical research on CAP-1002 treatment of DMD cardiac and skeletal myopathies is warranted.Classification of evidenceThis phase I/II study provides Class II evidence that for patients with DMD, intracoronary CAP-1002 is feasible and appears safe and potentially effective.

Ventricular structure and function

Myocardium is an exquisitely structured and thoroughly dynamic living continuum. Within this multidifferentiated continuum, the subcellular and cellular scale participants deform in quite different ways from the intact left ventricular (LV) wall, in which they are embedded. The different deformations of different scales are nevertheless compatible with one another and mutually supportive. This chapter considers examples of the principal deformations present at subcellular, cellular, tissue, and macroscopic scales. In the wall of the LV as a whole, the orientations of the cardiomyocytes are helically arranged. Moving inward through the depth of the LV wall, there is a gradual change of cardiomyocyte orientations from left-handed helical in subepicardial layers, transitioning through circumferential in the mid myocardium, to right-handed helical orientations in the subendocardial layer. Additionally, the cardiomyocytes are aggregated in microscopically visible laminae, comprised of sheetlets separated by collagen-lined cracks or shear layers, orientated obliquely to the local wall plane. The collective swivelling of all sheetlets, from more wall-parallel orientations in diastole to more wall-perpendicular in systole, contributes to the marked systolic thickening of the LV wall seen in vivo. With the onset of diastole, as cardiomyocytes relax, the reorientations of sheetlets may also have a further role in facilitating myocardial perfusion. In contrast to the LV, the human right ventricle remains relatively non-compact and trabeculated. This chapter considers the clinical implications of the non-laminar and arguably more primitive arrangements of cardiomyocytes in trabeculations and papillary muscles.

Long-term preservation of myocardial energetic in chronic hibernating myocardium

We previously reported that the myocardial energetic state, as defined by the ratio of phosphocreatine to ATP (PCr/ATP), was preserved at baseline (BL) in a swine model of chronic myocardial ischemia with mild reduction of myocardial blood flow (MBF) 10 wk after the placement of an external constrictor on the left anterior descending coronary artery. It remains to be seen whether this stable energetic state is maintained at a longer-term follow-up. Hibernating myocardium (HB) was created in minipigs ( n = 7) by the placement of an external constrictor (1.25 mm internal diameter) on the left anterior descending coronary artery. Function was assessed with MRI at regular intervals until 6 mo. At 6 mo, myocardial energetic in the HB was assessed by 31P-magnetic resonance spectrometry and myocardial oxygenation was examined from the deoxymyoglobin signal using 1H-magnetic resonance spectrometry during BL, coronary vasodilation with adenosine, and high cardiac workload with dopamine and dobutamine (DpDb). MBF was measured with radiolabeled microspheres. At BL, systolic thickening fraction was significantly lower in the HB compared with remote region (34.4 ± 9.4 vs. 50.1 ± 10.7, P = 0.006). This was associated with a decreased MBF in the HB compared with the remote region (0.73 ± 0.08 vs. 0.97 ± 0.07 ml·min−1·g, P = 0.03). The HB PCr/ATP at BL was normal. DpDb resulted in a significant increase in rate pressure product, which caused a twofold increase in MBF in the HB and a threefold increase in the remote region. The systolic thickening fraction increased with DpDb, which was significantly higher in the remote region than HB ( P < 0.05). The high cardiac workload was associated with a significant reduction in the HB PCr/ATP ( P < 0.02), but this response was similar to normal myocardium. Thus HB has stable BL myocardial energetic despite the reduction MBF and regional left ventricular function. More importantly, HB has a reduced contractile reserve but has a similar energetic response to high cardiac workload like normal myocardium.