Postconditioning attenuates no-reflow in STEMI patients

After acute myocardial infarction, the presence of no-reflow (or microvascular obstruction: MVO) has been associated with adverse left ventricular (LV) remodeling and worse clinical outcome. This study examined the effects of mechanical ischemic postconditioning on early and late MVO size in acute ST-elevation myocardial infarction (STEMI) patients. Fifty patients undergoing primary coronary angioplasty for a first STEMI with TIMI grade flow 0–1 and no collaterals were randomized to ischemic postconditioning (PC) (n = 25) or control (n = 25) groups. Ischemic PC consisted in the application of four consecutive cycles of a 1-min balloon occlusion, each followed by a 1-min deflation at the onset of reperfusion. Early (3 min post-contrast) and late (10 min post-contrast) MVO size were assessed by contrast-enhanced cardiac-MRI within 96 h after reperfusion. PC was associated with smaller early and late MVO size (3.9 ± 4.8 in PC versus 7.8 ± 6.6 % of LV in controls for early MVO, P = 0.02; and 1.8 ± 3.1 in PC versus 4.1 ± 3.9 % of LV in controls for late MVO; P = 0.01). This significant reduction was persistent after adjustment for thrombus aspiration, which neither had any significant effect on infarct size, nor on early or late MVO (P = NS for all). Attenuation of MVO was associated to infarct size reduction. Mechanical postconditioning significantly reduces MVO in patients with acute STEMI treated with primary angioplasty.     

Effect of bivalirudin compared with unfractionated heparin plus abciximab on infarct size and myocardial recovery after primary percutaneous coronary intervention: the horizons-AMI CMRI substudy

Background : Myocardial infarct size is a strong independent predictor of mortality in patients with ST‐elevation myocardial infarction (STEMI). In the Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS‐AMI) trial, bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor reduced cardiac mortality in STEMI patients, which was attributed to reduced major bleeding. Whether a possible reduction in infarct size with bivalirudin may have contributed to the enhanced survival with this agent is unknown. Methods : Cardiac magnetic resonance imaging was performed within 7 days and after 6 months in 51 randomized patients from a single center in HORIZONS‐AMI trial (N = 28 bivalirudin, N = 23 heparin plus abciximab). Infarct size, microvascular obstruction (MVO), left ventricular ejection fraction (LVEF), and LV end‐diastolic and end‐systolic volume indices were evaluated. Results : Infarct size was not significantly different after treatment with bivalirudin compared with heparin plus abciximab either within 7 days (median 9.3% [interquartile range 4.9%, 26.6%] vs. 20.0% [5.9%, 28.2%], P = 0.28) or at 6 months 6.7% [3.8%, 20.0%] vs. 8.2% [1.8%, 16.5%], P = 0.73). MVO was present in 28.6% versus 34.8% of patients respectively (P = 0.63). LVEF and LV volume indices also did not significantly differ between the two groups at either time period, nor were differences in myocardial recovery evident. Conclusions : In conclusion, in the HORIZONS‐AMI Cardiac magnetic resonance imaging (CMRI) substudy, cardiac magnetic resonance imaging within 7 days and at 6 months after primary percutaneous coronary intervention (PCI) did not demonstrate significant differences in infarct size, MVO, LVEF, or LV volume indices in patients treated with bivalirudin compared with unfractionated heparin plus abciximab. © 2011 Wiley Periodicals, Inc.     

Comparison of the angiographic myocardial blush grade with delayed‐enhanced cardiac magnetic resonance for the assessment of microvascular obstruction in acute myocardial infarctions

Background: Both myocardial blush grade (MBG) and cardiac magnetic resonance (CMR) are imaging tools that can assess myocardial reperfusion after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Objectives: We studied the relation between MBG and gadolinium‐enhanced CMR for the assessment of microvascular obstruction (MVO) in patients with acute ST‐elevated myocardial infarction (STEMI) treated by primary PCI. Material and Methods: MBG was assessed in 39 patients with initial TIMI 0 STEMI successfully treated by PCI, resulting in TIMI 3 flow grade and complete ST‐segment resolution. These MBG values were related to MVO determined by CMR, performed between 2 and 7 days after PCI. Left ventricular (LV) volumes were determined at baseline and at 6‐month follow‐up. Results: No statistical relation was found between MBG and MVO extent at CMR (P = 0.63). Regarding MBG 0 and 1 as a sign of MVO, the sensitivity and specificity of these scores were 53.8 and 75%, respectively. In this study, CMR determined MVO was the only significant LV remodeling predicting factor (β = 31.8; P = 0.002), whatever the MBG status was. Conclusion: MBG underestimates MVO after an optimal revascularization in AMI compared with CMR. This study suggests the superior accuracy of delayed‐enhanced magnetic resonance over MBG for the assessment of myocardial reperfusion injury that is needed in clinical trials, where the principal endpoint is the reduction of infarct size and MVO. © 2009 Wiley‐Liss, Inc.     

Relationship between QRS characteristics and delayed-enhancement cardiac magnetic resonance in patients with ischemic cardiomyopathy

BackgroundWe explored the relationship between QRS characteristics and myocardial phenotype by delayed-enhancement cardiac magnetic resonance (DE-CMR) in patients with coronary heart disease (CHD).Methods and resultsEighty five consecutive patients with CHD that were referred for DE-CMR evaluation constituted the study population. Of a total of 1445 left ventricular (LV) segments evaluated, 346 (23.9%) segments had fibrosis.Compared to patients without pathological Q waves, patients with pathological Q waves showed a higher number of segments with fibrosis (5.9 ± 3.1 vs. 2.7 ± 2.8, p < 0.001), and lower left ventricular ejection fraction (LVEF) (42.9 ± 13.6% vs. 51.8 ± 18.3, p = 0.01); whereas no significant differences were observed regarding LV size.When discriminated in according to the QRS duration tertiles, no significant differences were observed regarding the number of segments with fibrosis (p = 0.34), whereas the highest QRS tertile was related to the presence of a low LVEF (p = 0.005) and larger LV size (p = 0.01). QRS fragmentation (fQRS), defined as the presence of an R′ or notching in the nadir of the R wave or the S wave, or the presence of >1 R′ in 2 contiguous leads, was significantly related to LV size (LV end diastolic volume 153.6 ± 81.6 ml, vs. 111.5 ± 41.4 ml, p = 0.003), function (LVEF 43.2 ± 15.9% vs. 53.6 ± 16.3%, p = 0.005), and extent of fibrosis (5.1 ± 3.4 segments vs. 3.2 ± 3.1 segments, p = 0.01).ConclusionsIn the present study, fQRS was the only QRS-derived variable systematically and more closely related to LV size, LV systolic function, and to the presence and extent of fibrosis.     

Long-term Follow-up of Patients Undergoing Postconditioning During ST-Elevation Myocardial Infarction

Reperfusion injury may offset the optimal salvage of myocardium achieved during primary coronary angioplasty. Thus, coronary reperfusion must be combined with cardioprotective adjunctive therapies in order to optimize myocardial salvage and minimize infarct size. Forty-three patients with their first ST-elevation myocardial infarction were randomized to myocardial postconditioning or standard of care at the time of primary coronary angioplasty. Postconditioning was performed immediately upon crossing the lesion with the guide wire and consisted of four cycles of 30 s occlusion followed by 30 s of reperfusion. End-points included infarct size, myocardial perfusion grade (MPG), left-ventricular ejection fraction (LVEF), and long-term clinical events (death and heart failure). Despite similar ischemic times (≅4.5 h) (p = 0.9) a reduction in infarct size was observed among patients treated with the postconditioning protocol. Peak creatine phosphokinase (CPK), as well as its myocardial band (MB) fraction, was significantly lower in the postconditioning group when compared with the control group (CPK—control, 2,444 ± 1,928 IU/L vs. PC, 2,182 ± 1,717 IU/L; CPK-MB—control, 242 ± 40 IU/L vs. PC, 195 ± 33 IU/L; p = 0.64 and p < 0.01, respectively). EF in the postconditioning group was improved when compared with the control group (control, 43% ± 15 vs. PC, 52% ± 9; p = 0.05). After a mean follow-up of 3.4 years, a 6-point absolute difference in LVEF was still evident in the postconditioning group (p = 0.18). MPG was better among patients treated with the postconditioning protocol compared with control (2.5 ± 0.5 vs. 2.1 ± 0.6; p = 0.02). Due to the small sample size no significant differences in clinical events were detected (p value for death = 0.9; p value for heart failure = 0.2). A simple postconditioning protocol applied at the onset of mechanical reperfusion, resulted in reduction of infarct size, better epicardial and myocardial flow, and improvement in left ventricular function. The beneficial effects of postconditioning on cardiac function persist beyond 3 years.     

Effect of Intravascular Cooling on Microvascular Obstruction (MVO) in Conscious Patients with ST-Elevation Myocardial Infarction Undergoing Primary PCI: Results from the COOL AMI EU Pilot Study

ObjectiveCOOL AMI EU pilot was a multi-center, randomized controlled trial to assess feasibility and safety of rapid intravascular therapeutic hypothermia (TH) in conscious patients with anterior ST-elevation myocardial infarction (STEMI) undergoing primary PCI (PPCI). We report the effect of hypothermia upon microvascular obstruction (MVO).MethodsConscious patients with anterior STEMI and symptom duration <6 h were recruited and randomized to PPCI + TH or PPCI alone. TH was induced using the ZOLL® Proteus™ intravascular temperature management system and rapid infusion of 1 L of cold normal saline, with a target temperature of 32 °C. MVO was measured by cardiac magnetic resonance (CMR) at 4 to 6 days post-MI. MVO larger than 3.9% of LV was considered as extensive MVO.Results50 patients were randomized; mean age was 58 years, and 86% were men. At reperfusion, mean intravascular temperature for the TH group was 33.6 ± 1 °C. The presence of MVO was high and not different in both groups (74% vs. 77%, p = 0.79). The proportion of patients with extensive MVO was 11% in the TH group and 23% in the control group (OR 0.4 95%CI 0.07–2.35, p = 0.30). Patients with extensive MVO showed reduced EF at 4–6 days (34% versus 43%, p = 0.01). The percentage of patients with EF <35% at 30 days was 6% in the TH group versus 24% in the control group (p = 0.19).ConclusionIn the COOL-AMI Pilot Trial, the presence of MVO in both test groups was high and extensive MVO was related with reduced LVEF. The efficacy of therapeutic hypothermia (TH) in MVO reduction should be tested in a pivotal trial.     

Perfusion defect size predicts engraftment but not early retention of intra-myocardially injected cardiosphere-derived cells after acute myocardial infarction

Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [¹⁸F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and 1-h CDC retention (r = −0.65; P = 0.11). However, infarct size correlated significantly with 24-h engraftment (r = 0.75; P = 0.03). Residual perfusion at the injection site was not related to cell retention/engraftment. Larger infarcts are associated with improved CDC engraftment. This observation encourages further investigation of microenvironmental conditions after ischemic damage and their role in therapeutic cell survival.     

Impacts of nicorandil on infarct myocardium in comparison with nitrate: assessed by cardiac magnetic resonance imaging

In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p < 0.05), as well as the edema size on T2w CMR (r = 0.70, p < 0.05) in patients treated by nicorandil (28 patients). A similar correlation was seen between the peak CK level and the infarct size on DE CMR (r = 0.84, p < 0.05), as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate (24 patients). The maximum CK level was significantly lower in patients treated by nicorandil rather than nitrate (1991 ± 1402, 2785 ± 2121 IU/L, respectively, p = 0.03). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil rather than nitrate (17.7 ± 9.9, 21.9 ± 13.7 %; p = 0.03, 10.3 ± 6.0, 12.7 ± 6.9 %, p = 0.03, respectively). The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicorandil rather than nitrate (39.2, 64.7 %; p = 0.03; 2.2 ± 1.3, 3.4 ± 1.5 cm²; p = 0.02, respectively). Using CMR imaging, we demonstrated that the complementary use of intravenously and intracoronary administered nicorandil during PCI favorably acts more on the damaged myocardium after MI than nitrate. We need a further powered prospective study on the use of nicorandil.     

Comparison of the effects of nitroprusside versus nicorandil on the slow/no-reflow phenomenon during coronary interventions for acute myocardial infarction

Although slow/no-reflow is a serious problem complicating primary percutaneous coronary interventions (PCI) for acute myocardial infarction (AMI) and is associated with a poor prognosis, its efficacious treatment remains problematic. We compared the acute, in-hospital and long-term (1 year) effects of nitroprusside (NTP) with those of nicorandil (NC) on the slow/no-reflow phenomenon. Forty-nine of 442 consecutive patients with AMI who underwent primary PCI complicated by slow/no-reflow and who received intracoronary NTP (n = 25) or NC (n = 24) administration were studied. Both NTP and NC induced significant improvements in coronary flow, with increases in TIMI flow grade from 1.64 ± 0.62 to 2.74 ± 0.36 (p < 0.001) and 1.60 ± 0.86 to 2.23 ± 0.91 (p < 0.001), and in corrected TIMI frame count from 37.8 ± 15.1 to 13.7 ± 7.1 (p < 0.001) and 30.8 ± 20.7 to 19.3 ± 17.9 (p < 0.001), respectively. The degree of improvement in TIMI flow grade (post–pre/pre) and TIMI frame count (pre–post/pre) showed that NTP was more effective than NC (NTP vs. NC: 0.88 ± 0.79, 0.37 ± 0.37, p = 0.008; 0.59 ± 0.23, 0.36 ± 0.27, p = 0.003, respectively). Congestive heart failure did not tend to last beyond 3 days after onset in the NTP group, which was more than in the NC group, during hospitalization (1/25, 4/24, p = 0.143, respectively). At the 1-year follow-up, the NTP group tended to show more improvement than the NC group in MACE (5/25, 9/24, p = 0.175, respectively). NTP is a more effective treatment for slow/no-reflow associated with PCI in patients with AMI and may improve long-term clinical outcomes compared with NC.     

Distal protection device aggravated microvascular obstruction evaluated by cardiac MR after primary percutaneous intervention for ST-elevation myocardial infarction

Background

Protection of distal embolization by balloon occlusion and thrombus aspiration has not improved microvascular circulation nor decreased myocardial injury during primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) in randomized trials. In a prospective randomized trial, we investigated the mechanism of the poor effect of distal protection and thrombus aspiration (DP–TA) in 126 patients with STEMI.

Methods

Patients with first-diagnosed STEMI were randomly assigned to DP–TA pretreatment or conventional PCI (c-PCI). Primary endpoint was reduced left ventricular end-diastolic volume (LVEDV) measured by MRI at post-PCI and 6 months after PCI. Secondary end points were infarct ratio (infarct size to entire LV size) by delayed enhancement (DE), area at risk (AAR) ratio (AAR to entire LV size) by T2 high signal, microvascular occlusion index (MVO) ratio (MVO to entire LV size) by DE, and myocardial salvage index (MSI: (AAR − infarct size) ∗ 100 / AAR) using cardiac magnetic resonance imaging (MRI) within 3 days after PCI.

Results

Baseline characteristics of the patients including cardiovascular risk factors and lesion characteristics were similar between the two groups. DT–PA failed to improve LV remodeling at 6 months (LVEDV 140 ± 39 vs 133 ± 37 in c-PCI group, p = 0.418). Infarct ratio, AAR ratio and MSI were not statistically different between DP–TA group and c-PCI group. However, MVO ratio was significantly larger in DP–TA group than in c-PCI group (2.4 ± 2.7 vs 1.1 ± 1.9, p = 0.045).

Conclusion

DP–TA was potentially hazardous in primary PCI for STEMI by increasing MVO. DP–TA should not be used in STEMI.     

Angiographic perfusion score assessed in patients with acute myocardial infarction is correlated with cardiac magnetic resonance infarct size and N-terminal pro-brain natriuretic peptide in 6-month follow-up

Angiographic Perfusion Score (APS) proposed as a simple, angiographic score linking epicardial and myocardial perfusion parameters before and after percutaneous coronary intervention (PCI) is a predictor of short-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI. Aim of the study was to analyze the correlation between APS and both infarct size and left ventricular function in long-term follow-up. In a cohort of 68 patients with STEMI treated with PCI APS was calculated for infarct-related artery based on angiographic parameters and was defined as the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (0–3 points) and the TIMI myocardial perfusion grade (0–3 points) before and after PCI (range of points from 0 to 12). Full perfusion was defined as APS ≥ 10. Cardiac magnetic resonance (CMR) parameters and N-terminal pro-brain natriuretic peptide (NT pro-BNP) were assessed at 6 months. Results: Median APS was 7.5 points. APS ≥ 10 was present in 42% of patients. The significant correlation was found between APS and: CMR infarct size (r = − 0.48; P = 0.0001), CMR left ventricular (LV) ejection fraction (r = 0.5; P = 0.002), LV end-diastolic volume index (r = − 0.37; P = 0.004), LV end-systolic volume index (r = −0.41; P = 0.001), NT pro-BNP (r = − 0.5; P = 0.02). Patients with APS ≥ 10 had significantly lower infarct size, LV volumes, higher EF and lower NT pro-BNP. APS assessed in patients with STEMI treated with PCI is a good predictor of infarct size and left ventricular function in 6-month follow-up.     

Prognostic impact of interim positron emission tomography in mantle cell lymphoma patients treated with frontline R-CHOP

Although ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end-of-treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five-year overall survival (OS) [hazard ratio (HR) 7·84, P < 0·0001] and poor five-year progression-free survival (PFS) (HR 3·34, P < 0·0001). OS and PFS were more favourable in the order early metabolic responder (iPET^neg → ePET^neg), delayed responder (iPET^pos → ePET^neg), loss-metabolic responder (iPET^neg → ePET^pos), and never-metabolic responder (iPET^pos → ePET^pos). In the autologous haematopoietic stem cell transplantation (auto-HSCT)-fit subgroup, OS was more favourable in the order early metabolic responders, delayed metabolic responders, and non-metabolic responders, with a marginal trend toward statistical significance (HR 3·41, P = 0·051), and PFS was significantly superior in early metabolic responders (HR 4·43, P = 0·002). In a group that was ineligible for auto-HSCT, OS and PFS were significantly superior in early metabolic responders. Our results suggested that iPET is of prognostic value and an independent predictor of survival in MCL patients receiving frontline R-CHOP. Therefore, prospective clinical trials of iPET-guided treatment strategies for these patients are warranted.     

Long-Term Incremental Prognostic Value of Cardiovascular Magnetic Resonance After ST-Segment Elevation Myocardial Infarction: A Study of the Collaborative Registry on CMR in STEMI

Objectives

This study sought to investigate whether early post-infarction cardiac magnetic resonance (CMR) parameters provide additional long-term prognostic value beyond traditional outcome predictors in ST-segment elevation myocardial infarction (STEMI) patients.

Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetes mellitus

To elucidate the factors involved in the reduced survival rate of diabetic patients after acute myocardial infarction (AMI), we prospectively evaluated 100 patients with well-documented diabetes and 426 control patients. We characterized infarct size and analyzed the incidence and severity of congestive heart failure (CHF) and subsequent death with respect to infarct size. The extent of the index infarct was less in diabetic compared to nondiabetic patients, 16.2 ± 2.2 CK-gm-eq/m² compared with 19.2 ± 0.9 (p < 0.02). However, CHF was more prevalent in diabetic patients (31.2% of the diabetic patients compared to 15.7%). The difference was most prominent in diabetic patients who had sustained prior infarction (50% compared to 16%), but was evident also in diabetic patients with initial infarction (26% compared to 16%). The mortality rate was greater in diabetic patients (p < 0.04). When diabetic and nondiabetic patients were stratified with respect to the presence or absence of CHF, survival curves were comparable. The increased incidence of CHF despite a smaller infarct size suggests that additional factors must contribute to myocardial dysfunction and the resultant excess in mortality.     

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction

This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia–reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC). Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC). This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC. In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia–reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent). This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent). In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPC_eff = 0.36 ± 0.03 μM vs C _eff = 0.04 ± 0.04 μM, n = 4, p < 0.001). Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia–reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent). In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors.

     

Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT.     

Tissue plasminogen activator antigen predicts medium-term left ventricular end-systolic volume after acute myocardial infarction

Von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) predict adverse cardiovascular outcome following acute myocardial infarction (AMI) and are weakly associated with pre-discharge left ventricular ejection fraction (LVEF). We examined the relationships between VWF, t-PA antigen, matrix metalloproteinase (MMP)-2,-3, and -9, and B-type natriuretic peptide (BNP), and their predictive effect on serial change in LV volumes in a cohort of patients admitted with AMI. Plasma VWF, t-PA antigen, MMP-2,-3,-9, and BNP were measured at a mean 46 h after AMI in 100 patients (mean age 58.9 ± 12 years, 77% male) with depressed LVEF. Cardiac magnetic resonance (CMR) imaging was then performed. Biomarker measurement and CMR were repeated at 12 and 24 weeks. Plasma concentrations of VWF, BNP and MMP-9 were elevated while t-PA antigen concentration was at the upper limits of normal; over 24 weeks VWF, t-PA antigen, MMP-9 and BNP decreased significantly. Baseline VWF correlated with BNP (r = 0.35, P < 0.001) and MMP-3 (r = 0.24, P = 0.019) as did t-PA antigen (r = 0.27, P = 0.007 for BNP; r = 0.40, P < 0.001 for MMP-3). t-PA antigen, VWF, MMP-3 and BNP were univariate predictors of LV end-systolic volume at 24 weeks; tPA antigen and BNP remained significant independent predictors on multivariate analysis. t-PA antigen and VWF are related to medium-term LV volumes after AMI, and to MMP-3. This novel link between the coagulation-fibrinolysis system and matrix turnover merits further study in understanding the pathophysiology of adverse ventricular remodeling after AMI.     

Analysis of left ventricular fluid dynamics in dilated cardiomyopathy by echocardiographic particle image velocimetry

Objective

The aim was to analyze left ventricular (LV) fluid dynamics in dilated cardiomyopathy (DCM) by using echocardiographic particle image velocimetry (E‐PIV).

Methods

Twenty patients with DCM and twenty healthy volunteers were examined. LV ultrasound contrast was administered by intravenous bolus injection. At least three dynamic contrast‐enhanced echocardiographic images of cardiac cycles from apical three‐chamber view and four‐chamber view were obtained. The acquired echocardiographic image loops were processed off line by HyperFlow.

Results

In healthy hearts, the filling flow in the left ventricle finally comes to be a single large clockwise vortex, which smoothly redirects the blood to the outflow tract. Meanwhile, aberrant flow patterns are observed in the patients with DCM. In the DCM group, the vortex area (0.237 ± 0.063 vs 0.196 ± 0.129, P = .029), vortex depth (0.396 ± 0.134 vs 0.293 ± 0.143, P = .025), and vortex length (0.534 ± 0.089 vs 0.435 ± 0.176, P = .004) are significantly higher. The flow force angle (29.979 ± 8.208 vs 35.896 ± 6.044, P = .013) is significantly lower, and energy dissipation (0.975 ± 0.552 vs 0.578 ± 0.295, P = .006) is significantly higher. A negative linear relation is indicated between the following pairs of parameters: vortex depth and LV ejection fraction (EF) (r = ?.350, P = .027); vortex length and LV EF (r = ?.321, P = .044); energy dissipation and LV EF (r = ?.523, P = .001). A positive linear relation is indicated between flow force angle and LV EF (r = .365, P = .021).

Conclusion

E‐PIV can effectively and quantitatively evaluate LV fluid dynamics in patients with DCM. LV fluid dynamics and LV systolic function interact with and affect each other.     

Repeated Low-dose of Erythropoietin is Associated with Improved Left Ventricular Function in Rat Acute Myocardial Infarction Model

Objective To evaluate the potential protective affects of Epo on left ventricular (LV) function and remodeling after acute myocardial infarction (MI). Methods Epo was injected into the peritoneum of male Wistar rats (250 g) during 6 weeks post induction of MI. Rats were divided into five groups: MI treated with single high dose (MT1, 5,000 U/kg, n = 10), single high dose (5,000 U/kg) and repeated high doses (MTHi, 1,000 U/kg twice a week; n = 8), or single high dose (5,000 U/kg) and repeated low doses (MTLo, 750 U/kg once a week, n = 10), MI non-treated (MNT, n = 10), sham (S, n = 5). Echocardiography was performed 3.6 ± 1.5 days and 43.7 ± 2.3 days post MI. Collagen deposition and infarct size were measured on histological sections using computerized image analysis. Apoptosis was assessed by ApopTag staining. Results Baseline fractional shortening (FS) was similar between groups. Six weeks after MI the FS of MTLo (26.9%) was significantly higher compared to MNT (17.8%), MT1 (19.5%) and MTH (22.3%) (p = 0.01). However, remodeling indices (end diastolic and end systolic areas, LV circumference) did not improve in the Epo groups, and even worsened in the MTHi group. There was significantly less collagen staining in non-infarct areas in MT1 and MTHi groups compared to MNT and MTLo (0.38 ± 0.3%, 0.49 ± 0.34%, vs 0.89 ± 0.41%, 0.95 ± 0.33%, respectively, p < 0.001). The number of ApopTag positive nucleus was significantly higher in the MNT group compared to the MT1, MTHi, MTLo groups (14.4 ± 8, 7.6 ± 4, 5.8 ± 7, 4.8 ± 5, respectively, p = 0.01 for trend). Conclusion Repeated low doses of Epo after MI improved LV function, but the role of Epo on remodeling is not clear. It did not reduce left ventricular indices, but reduces fibrosis and apoptosis. High Epo doses reduced LV function and aggravated remodeling.     

Noctural dipping status and left ventricular hypertrophy: A cardiac magnetic resonance imaging study

We investigate the impact of dipper status on cardiac structure with cardiovascular magnetic resonance (CMR). Ambulatory blood pressure monitoring and 1.5T CMR were performed in 99 tertiary hypertension clinic patients. Subgroup analysis by extreme dipper (n = 9), dipper (n = 39), non‐dipper (n = 35) and reverse dipper (n = 16) status was performed, matched in age, gender and BMI. Left ventricular (LV) mass was significantly higher for extreme dippers than dippers after correction for covariates (100 ± 6 g/m² vs 79 ± 3 g/m², P = .004). Amongst extreme dippers and dippers (n = 48), indexed LV mass correlated positively with the extent of nocturnal blood pressure dipping (R = .403, P = .005). On post‐hoc ANCOVA, the percentage of nocturnal dip had significant effect on indexed LV mass (P = .008), but overall SBP did not (P = .348). In the tertiary setting, we found a larger nocturnal BP drop was associated with more LV hypertrophy. If confirmed in larger studies, this may have implications on nocturnal dosing of anti‐hypertensive medications.