Cross-talk between the heart and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: A prospective study

Objectives

Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition in CC and that a progressive loss of fat free mass (FFM) and fat mass (FM) takes place.

Methods

Body composition with regard to FFM, FM, and body fat distribution was assessed by dual energy X-ray absorptiometry (DXA) in 19 non-diabetic patients with chronic heart failure (CHF) and CC and 38 controls (non-cachectic CHF and individuals with prior myocardial infarction-both n = 19) who were followed for 12 months. Biomarkers of neurohormonal stimulation, inflammation, and endothelial dysfunction were measured.

Results

N-terminal proBNP (NT-proBNP), midregional proANP (MR-proANP), and total adiponectin were elevated in CHF (p < 0.001) and correlated inversely to BMI and FM. An inverse correlation was observed between pro-adrenomedullin (MR-proADM) and FFM. During follow up body weight was unaltered in all groups even though FM increased by 1.35 kg (p < 0.05) and FFM decreased by 0.5 kg (p < 0.05) in CC patients. The latter correlated inversely to baseline NT-proBNP, MR-proANP, and MR-proADM (p < 0.05). No correlation to changes in FM was found.

Conclusions

FM was associated with plasma NPs and total adiponectin at baseline; whereas changes in FM and FFM did not correlate to changes in NPs or adiponectin during follow up. Prospectively, FFM decreased but FM increased, despite stable body weight in CC.     

Mid-regional pro-adrenomedullin in the early evaluation of acute chest pain patients

Background

The purpose of this study was to investigate the utility of mid-regional pro-adrenomedullin (MR-proADM) in the early diagnosis and risk stratification of patients with acute chest pain in comparison with established and novel biomarkers and risk scores.

Methods

In this prospective, observational, international, multi-center trial (APACE), MR-proADM was determined in 1179 unselected patients with acute chest pain. Patients were followed for 24 months.

Results

MR-proADM concentrations at presentation were higher in patients with AMI (median: 0.78 nmol/l, IQR 0.60–1.13) than in patients with other diagnoses (0.64 nmol/l, IQR 0.49–0.86 nmol/l; p < 0.001). The diagnostic accuracy of MR-proADM for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.66. Adding MR-proADM to hs-cTnT could not improve its diagnostic accuracy for AMI (p = 0.431). Seventy-six percent of all deaths occurred in the fourth quartile of MR-proADM (> 0.90 nmol/l). Adding MR-proADM to the TIMI-score (AUC 0.87) predicted 1-year mortality more accurately than the TIMI-score alone (AUC 0.82; p < 0.001). Net reclassification improvement (TIMI vs. additionally MR-proADM) amounted to 0.137 (p = 0.012). MR-proADM had higher prognostic accuracy as compared to hs-cTnT in patients with AMI (p = 0.015) and in those without AMI (p = 0.003). MR-proADM at presentation was tantamount to GRACE score and BNP as to its prognostic accuracy for mortality. The AUC for the prediction of cardiovascular events amounted to 0.63.

Conclusions

While MR-proADM does not have clinical utility in the early diagnosis of AMI or predicting cardiovascular events in patients with acute chest pain, it may provide prognostic value for all-cause mortality.     

Angiographic assessment of myocardial perfusion in Tako-Tsubo syndrome

Objectives

To angiographically assess myocardial perfusion in patients with Tako-Tsubo syndrome (TTS) in comparison with control individuals and patients with ST-elevation myocardial infarction (STEMI).

Background

Coronary microvascular dysfunction has been proposed as the pathophysiological mechanism underlying TTS.

Methods

We retrospectively selected consecutive TTS patients showing typical left ventricular (LV) apical dysfunction admitted to our Department in the period 2007–2011 (n = 25). We also enrolled an age and gender-matched control group showing normal coronary arteries (CTR, n = 25), patients with STEMI undergoing primary percutaneous intervention with myocardial reperfusion (SR, n = 25) or microvascular obstruction (SMVO, n = 25). TIMI flow, TIMI frame count (TFC) and both qualitative and quantitative myocardial blush grade in LV apex were assessed. Specifically, myocardial perfusion was quantitatively evaluated using ‘Quantitative Blush Evaluator’ (QuBE), an open source software previously validated in the setting of STEMI.

Results

In TTS, TIMI flow on the LAD was significantly lower and TFC significantly higher compared to CTR and SR (p = 0.008 for both), while it did not significantly differ compared to SMVO (p = 0.06). In TTS, MBG was significantly lower than that in CTR and SR (p = 0.001 for both), while it was significantly higher than that in SMVO (p < 0.001). In TTS, QuBE score was significantly lower than that in CTR and SR (p = 0.001 for both) and higher than in SMVO (p = 0.02).

Conclusions

Our data indicate that myocardial perfusion assessed during angiography is more impaired in patients with TTS than in patients with STEMI exhibiting myocardial reperfusion, while it is less impaired than in patients with STEMI exhibiting MVO.     

Osteoprotegerin in ST-elevation myocardial infarction: Prognostic impact and association with markers of myocardial damage by magnetic resonance imaging

Background/Objectives

For osteoprotegerin (OPG), a cytokine of the tumor necrosis factor superfamily, the prognostic impact in stable coronary artery disease and acute coronary syndromes has been shown recently. In acute ST-elevation myocardial infarction (STEMI) data on the correlation to myocardial damage by cardiac magnetic resonance imaging (CMR) or clinical outcome are lacking.

Methods

We studied 221 consecutive patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI) within 12 h after symptom onset. Serum levels of OPG were determined from samples collected before PCI (OPG0), at 24 (OPG1) and 48 h (OPG2) after reperfusion. CMR studies for assessment of infarct size, reperfusion injury/microvascular obstruction and myocardial salvage were performed within one week after infarction. Long-term clinical follow-up for major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or new onset of congestive heart failure, was performed 18.2 (interquartile range of 9.2–21.2) months after the index event.

Results

OPG levels ≥ 75th percentile were associated with significantly larger infarcts, lower myocardial salvage index and greater extent of microvascular obstruction in CMR as compared to OPG levels < 75th percentile. The MACE rate for patients with OPG levels in the highest quartile was also significantly higher. In a multivariable model adjusted for known risk factors, OPG1 as a continuous variable was independently predictive for MACE.

Conclusion

OPG serum levels collected 24 h after infarction are independent predictors of MACE in acute STEMI patients. High OPG levels are associated with a greater extent of myocardial damage and lower myocardial salvage by CMR.     

Comprehensive Prognosis Assessment by CMR Imaging After ST-Segment Elevation Myocardial Infarction

Background

Although the prognostic value of findings from cardiac magnetic resonance (CMR) imaging has been established in single-center center studies in patients with ST-segment elevation myocardial infarction (STEMI), a large multicenter investigation to evaluate the prognostic significance of myocardial damage and reperfusion injury is lacking.

Objectives

The aim of this study was to assess the prognostic impact of CMR in an adequately powered multicenter study and to evaluate the most potent CMR predictor of hard clinical events in a STEMI population treated by primary percutaneous coronary intervention (PCI).

Methods

We enrolled 738 STEMI patients in this CMR study at 8 centers. The patients were reperfused by primary PCI <12 h after symptom onset. Central core laboratory–masked analyses for quantified left ventricular (LV) function, infarct size (IS), microvascular obstruction (MO), and myocardial salvage were performed. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events.

Results

Patients with cardiovascular events had significantly larger infarcts (p < 0.001), less myocardial salvage (p = 0.01), a larger extent of MO (p = 0.009), and more pronounced LV dysfunction (p < 0.001). In a multivariate model that included clinical and other established prognostic parameters, MO remained the only significant predictor in addition to the TIMI (Thrombolysis In Myocardial Infarction) risk score. IS and MO provided an incremental prognostic value above clinical risk assessment and LV ejection fraction (c-index increase from 0.761 to 0.801; p = 0.036).

Conclusions

In a large, multicenter STEMI population reperfused by primary PCI, CMR markers of myocardial damage (IS and especially MO) provide independent and incremental prognostic information in addition to clinical risk scores and LV ejection fraction. (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction [AIDA STEMI]; NCT00712101).     

Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis,adverse left ventricular remodeling and relationship with microvascular obstruction

Background

T2 weighted cardiovascular magnetic resonance (CMR) can detect intramyocardial hemorrhage (IMH) after ST-elevation myocardial infarction (STEMI). The long-term prognostic value of IMH beyond a comprehensive CMR assessment with late enhancement (LE) imaging including microvascular obstruction (MVO) is unclear. The value of CMR-derived IMH for predicting major adverse cardiac events (MACE) and adverse cardiac remodeling after STEMI and its relationship with MVO was analyzed.

Methods

CMR including LE and T2 sequences was performed in 304 patients 1 week after STEMI. Adverse remodeling was defined as dilated left ventricular end-systolic volume indexes (dLVESV) at 6 months CMR.

Results

During a median follow-up of 140 weeks, 47 MACE (10 cardiac deaths, 16 myocardial infarctions, 21 heart failure episodes) occurred. Predictors of MACE were ejection fraction (HR .95 95% CI [.93–.97], p = .001, per %) and IMH (HR 1.17 95% CI [1.03–1.33], p = .01, per segment). The extent of MVO and IMH significantly correlated (r = .951, p < .0001). dLVESV was present in 40% of patients. CMR predictors of dLVESV were: LVESV (OR 1.11 95% CI [1.07–1.15], p < .0001, per ml/m²), infarct size (OR 1.05 95% CI [1.01–1.09], p = .02, per %) and IMH (OR 1.54 95% CI [1.15–2.07], p = .004, per segment). Addition of T2 information did not improve the LE and cine CMR-model for predicting MACE (.744 95% CI [.659–.829] vs. .734 95% CI [.650–.818], p = .6) or dLVESV (.914 95% CI [.875–.952] vs. .913 95% CI [.875–.952], p = .9).

Conclusions

IMH after STEMI predicts MACE and adverse remodeling. Nevertheless, with a strong interrelation with MVO, the addition of T2 imaging does not improve the predictive value of LE-CMR.     

Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated myocardial infarction undergoing primary coronary intervention: A prospective,multicenter study

Objective

The pre-procedural neutrophil to lymphocyte ratio (N/L) is associated with adverse outcomes among patients with coronary artery disease but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. This study evaluated the relations between pre-procedural N/L ratio and the in-hospital and long-term outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PCI).

Methods

A total of 682 STEMI patients presented within the first 6 h of symptom onset were enrolled and stratified according to tertiles of N/L ratio based on the blood samples obtained in the emergency room upon admission.

Results

The mean follow-up period was 43.3 months (1–131 months). In-hospital in-stent thrombosis, non-fatal myocardial infarction, and cardiovascular mortality increased as the N/L tertile ratio increased (p < 0.001, p < 0.001, p = 0.003, respectively). Long-term in-stent thrombosis, non-fatal myocardial infarction and cardiovascular mortality also increased as the N/L ratio increased (p < 0.001, p < 0.001, p = 0.002, respectively). On multivariate analysis, N/L ratio remained an independent predictor for both in-hospital (OR 1.189, 95% CI 1.000–1.339; p < 0.001) and long-term major (OR 1.228, 95% CI 1.136–1.328; p < 0.001) adverse cardiac events.

Conclusion

The N/L ratio was an independent predictor of both in-hospital and long-term adverse outcomes among STEMI patients undergoing primary PCI. Our findings suggest that this inexpensive, universally available hematological marker may be incorporated into the current established risk assessment model for STEMI.     

Does residual aortic regurgitation after transcatheter aortic valve implantation increase mortality in all patients? The importance of baseline natriuretic peptides

Background

Aortic regurgitation (AR) is an important complication of transcatheter aortic valve implantation (TAVI) and even moderate AR is associated with increased mortality after TAVI. The association with decreased survival is unclear. We aimed to analyse the impact of AR after TAVI as a function of baseline NT-proBNP.

Methods

We included 236 consecutive patients implanted in our centre with the SAPIEN and SAPIEN XT valves, via the transfemoral route. AR was evaluated by transthoracic echocardiography. NT-proBNP was measured 24 h before implantation and patients were divided according to the median value.

Results

Median age was 85 years (80–89) and 137 (58.1%) were women. Patients with high NT-proBNP had lower left ventricular ejection fraction: 52% (35–65) vs. 63% (55–70), p < 0.001, larger telediastolic diameters: 56 mm (49–61) vs. 52 mm (46–56), p = 0.01, and more severe aortic stenosis: 0.62 ± 0.15 cm² vs. 0.70 ± 0.2 cm², p < 0.001. Pre-procedural moderate or severe AR (42% vs. 26%, p = 0.013) and mitral regurgitation (56% vs. 36%, p = 0.004) were more common in the high NT-proBNP group. After TAVI, moderate or severe AR occurred in 26% of patients and was associated with increased 2-year mortality only in the low NT-proBNP group, while patients in the high NT-proBNP group were not affected.

Conclusions

Moderate or severe AR after TAVI was not associated with increased 2-year mortality in patients with high baseline NT-proBNP. Our data suggest that the impact of AR after TAVI is absent in patients with significant pre-procedural AR or mitral regurgitation and more severe aortic stenosis.     

MRI-assessed regional pulse wave velocity for predicting absence of regional aorta luminal growth in marfan syndrome

Background

In patients with Marfan syndrome (MFS), increased aortic wall stiffening may lead to progressive aortic dilatation. Aortic Pulse Wave Velocity (PWV), a marker of wall stiffness can be assessed regionally, using in-plane multi-directional velocity-encoded MRI. This study examined the diagnostic accuracy of regional PWV for prediction of regional aortic luminal growth during 2-year follow-up in MFS patients.

Methods

In twenty-one MFS patients (mean age 36 ± 15 years, 11 male) regional PWV and aortic luminal areas were assessed by 1.5 T MRI. At 2-year follow-up, the incidence of luminal growth, defined as mean luminal diameter increase > 2 mm was determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta, S4, supra-renal and S5, infra-renal abdominal aorta). Regional PWV at baseline was considered increased when exceeding age-related normal PWV (healthy volunteers (n = 26; mean age 30 ± 10 years, 15 male)) by two standard-errors. Sensitivity and specificity of regional PWV-testing for prediction of regional luminal growth were determined.

Results

Regional PWV at baseline was increased in 17 out of 102 segments (17%). Significant luminal growth at follow-up was reported in 14 segments (14%). The specificity of regional PWV-testing was ≥ 78% for all aortic segments, sensitivity was ≤ 33%.

Conclusions

Regional PWV was significantly increased in MFS patients as compared to healthy volunteers within similar age range, in all aortic segments except the ascending aorta. Furthermore, regional PWV-assessment has moderate to high specificity for predicting absence of regional aortic luminal growth for all aortic segments in MFS patients.     

A mismatch index based on the difference between measured left ventricular ejection fraction and that estimated by infarct size at three months following reperfused acute myocardial infarction

Background and Aim

The reduction of left ventricular ejection fraction (LVEF) following ST-segment elevation myocardial infarction (STEMI) is a result of infarcted myocardium and may involve dysfunctional but viable myocardium. An index that may quantitatively determine whether LVEF is reduced beyond the expected value when considering only infarct size (IS) has previously been presented based on cardiac magnetic resonance (CMR). The purpose of this study was to introduce the index based on the electrocardiogram (ECG) and compare indices based on ECG and CMR.

Method and Results

In 55 patients ECG and CMR were obtained 3 months after STEMI treated with primary percutaneous coronary intervention. Significant, however moderate inverse relationships were found between measured LVEF and IS. Based on IS and LVEF an IS estimated LVEF was derived and an MI–LVEF mismatch index was calculated as the difference between measured LVEF and IS estimated LVEF. In 41 (74.5%) of the patients there was agreement between the ECG and CMR indices in regards to categorizing indices as > 10 or ≤ 10 and generally no significant difference was detected, mean difference of 1.26 percentage points (p = 0.53).

Conclusion

The study found an overall good agreement between MI–LVEF mismatch indices based on ECG and CMR. The MI–LVEF mismatch index may serve as a tool to identify patients with potentially reversible dysfunctional but viable myocardium, but future studies including both ECG and CMR are needed.     

High post-clopidogrel platelet reactivity assessed by a point-of-care assay predicts long-term clinical outcomes in patients with ST-segment elevation myocardial infarction who underwent primary coronary stenting

Background

Recent studies have shown that post-clopidogrel high platelet reactivity (HPR), assessed by a point-of-care assay, is associated with a higher risk of adverse events after percutaneous coronary intervention (PCI). We assessed the clinical impact of HPR by the VerifyNow P2Y12 point-of-care assay in 181 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary PCI with drug-eluting stents (DES) at 3 hospitals.

Methods

The primary endpoint of the study was the 12-month major adverse cardiovascular events (MACE), which comprised cardiovascular death, nonfatal MI and ischemic stroke. All patients received a single loading dose of 600 mg clopidogrel and 300 mg aspirin followed by a daily maintenance dose of 75 mg clopidogrel and 100 mg aspirin.

Results

A P2Y12 reaction unit (PRU) ≥ 282 (AUC 0.719, 95% CI 0.588–0.851, p = 0.004, sensitivity 68.8%, specificity 73.8%) was the optimal cut-off value in predicting 12-month MACE by receiver operating characteristic curve analysis. Occurrence of MACE was significantly more frequent in patients with HPR (PRU ≥ 282) compared to patients without HPR (20.4% vs. 3.9%, HR 6.24, 95% CI 2.05–18.99, p = 0.001). By multivariate analysis, HPR (HR 3.84, 95% CI 1.17–12.58, p = 0.026) and elderly patients above 80 years of age (HR: 8.13, 95% CI 1.79–37.03, p = 0.007) were found to be the significant predictors of 12-month MACE. The MACE-free survival rate was significantly lower in patients with HPR compared to patients without HPR (p < 0.001).

Conclusion

HPR assessed by a point-of-care assay was able to predict 12-month MACE in patients with STEMI who underwent primary PCI with DES.     

Prognostic implications of quantitative evaluation of baseline Q-wave width in ST-segment elevation myocardial infarction

Objectives

To evaluate quantitative relationships between baseline Q-wave width and 90-day outcomes in ST-segment elevation myocardial infarction (STEMI).

Background

Baseline Q-waves are useful in predicting clinical outcomes after MI.

Methods

3589 STEMI patients were assessed from a multi-centre study.

Results

1156 patients of the overall cohort had pathologic Q-waves. The 90-day mortality and the composite of mortality, congestive heart failure (CHF), or cardiogenic shock (p < 0.001 for both outcomes) rose as Q-wave width increased. After adapting a threshold ≥ 40 ms for inferior and ≥ 20 ms for lateral/apical MI in all patients (n = 3065) with any measureable Q-wave we found hazard ratios (HR) for mortality (HR: 2.44, 95% confidence interval (CI) (1.54–3.85), p < 0.001) and the composite (HR: 2.32, 95% CI (1.70–3.16), p < 0.001). This improved reclassification of patients experiencing the composite endpoint versus the conventional definition (net reclassification index (NRI): 0.23, 95% CI (0.09-0.36), p < 0.001) and universal MI definition (NRI: 0.15, 95% CI (0.02–0.29), p = 0.027).

Conclusions

The width of the baseline Q-wave in STEMI adds prognostic value in predicting 90-day clinical outcomes. A threshold of ≥ 40 ms in inferior and ≥ 20 ms for lateral/apical MI enhances prognostic insight beyond current criteria.     

Improvement of myocardial function and perfusion after successful percutaneous revascularization in patients with chronic total coronary occlusion

Background

Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) of a coronary artery can provide benefits in terms of myocardial function and survival but the procedure is complex and the success rate is relatively low. To assess these benefits, myocardial function, ischemia and viability should be clearly determined by means of a reliable diagnostic test. This study aimed to assess ventricular function and myocardial ischemia before and after PCI for CTO using cardiac magnetic resonance (CMR). NYHA functional class was also assessed before and after PCI.

Methods and results

CMR studies were performed in 43 consecutive patients (7 females; aged 64 ± 9.6 y.o.) with CTO scheduled for PCI and repeated 6 months post-PCI. PCI was successful in 33 (77%) of them. In this group CMR had shown inducible perfusion defects in 26 (79%) before PCI, while they were observed in 10 (30%) post-PCI CMR study (p < 0.001). The number of segments showing inducible perfusion defect (3.4 ± 2 prevs. 2.9 ± 4.5 post-PCI, p = 0.002) was significantly reduced in this group. Regional contractile function of segments showing viability also improved significantly in the group with successful CTO PCI compared to the group with an unsuccessful procedure. NYHA functional class for angina also improved in patients with successful revascularization while it remained unchanged in the group with unsuccessful procedures.

Conclusions

A successful CTO PCI leads to a reduction in inducible myocardial ischemia and to an improvement in regional wall motion, which results in clinical improvement.     

Positive effect of intravenous iron-oxide administration on left ventricular remodelling in patients with acute ST-elevation myocardial infarction – A cardiovascular magnetic resonance (CMR) study

Objectives

This study investigated the safety profile and potential “therapeutic” effect of intravenous ultrasmall superparamagnetic iron-oxide (USPIO)-based iron administration regarding infarct healing in patients with ST-elevation myocardial infarction (STEMI). USPIO-administration was recently shown to enable an improved characterization of myocardial infarct pathology in acute STEMI patients.

Materials and Methods

Seventeen study patients (IRON, 54 ± 9 yrs, 88% male) and 22 matched controls (CONTROL, 57 ± 9 yrs, 77% male) both with primary reperfused STEMI underwent multi-parametric CMR studies in the first week and three months after acute MI. Only IRON patients received a single intravenous bolus of 510 mg elemental iron as ferumoxytol (Feraheme^TM) within four days following acute MI.

Results

Three months later, all patients were alive and there were no adverse cardiac events. Significant improvement in left ventricular (LV) ejection fraction (IRON: 53 ± 10% to 59 ± 9%, p = 0.002; CONTROL: 54 ± 6% to 57 ± 10%, p = 0.005) as well as shrinkage of infarct size were seen in both groups at follow-up. There was a more pronounced decrease in infarct size in the IRON group (IRON: − 10.3 ± 5.4% vs. CONTROL: − 7.0 ± 8.4%, p = 0.050) in addition to a significant decrease in both endocardial extent and prevalence of transmural infarctions in IRON but not in CONTROL patients. A significant decrease in LV end systolic volume was only seen in the IRON group (71 ± 25 mL to 59 ± 25 mL, p = 0.002).

Conclusions

Intravenous iron administration in acute STEMI patients seems to be associated with an improved infarct healing and a beneficial global left ventricular remodelling. These findings together with the good safety profile make USPIO-based iron administration a promising future candidate as a “diagnostic” and “therapeutic” adjunctive solution in acute MI management.     

Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine

Background

Ischemic postconditioning (PCON) appears as a potentially beneficial tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an experimental swine model.

Methods

A prospective randomized study in patients and an experimental study in swine were carried out in two university hospitals in Spain. 101 consecutive STEMI patients were randomized to undergo primary angioplasty followed by PCON or primary angioplasty alone (non-PCON). Using late gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO were quantified (% of left ventricular mass). In swine, using an angioplasty balloon-induced anterior STEMI model, MVO was defined as the % of area at risk without thioflavin-S staining.

Results

In patients, PCON (n = 49) in comparison with non-PCON (n = 52) did not significantly reduce MVO (0 [0–1.02]% vs. 0 [0–2.1]% p = 0.2) or IS (18 ± 13% vs. 21 ± 14%, p = 0.2). MVO (> 1 segment in the 17-segment model) occurred in 12/49 (25%) PCON and in 18/52 (35%) non-PCON patients, p = 0.3. No significant differences were observed between PCON and non-PCON patients in left ventricular volumes, ejection fraction or the extent of hemorrhage. In the swine model, MVO occurred in 4/6 (67%) PCON and in 4/6 (67%) non-PCON pigs, p = 0.9. The extent of MVO (10 ± 7% vs. 10 ± 8%, p = 0.9) and infarct size (23 ± 14% vs. 24 ± 10%, p = 0.8) was not reduced in PCON compared with non-PCON pigs.

Conclusions

Ischemic postconditioning does not significantly reduce microvascular obstruction in ST-segment elevation myocardial infarction.Clinical Trial Registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT01898546.     

Temporal trends in all-cause mortality of smokers versus non-smokers hospitalized with ST-segment elevation myocardial infarction

Background/objectives

Over the past decade, the development of novel management strategies has resulted in improved outcomes among patients hospitalized with ST-segment myocardial infarction (STEMI). The aim of the present study was to compare temporal trends in the mortality of smokers versus non-smokers admitted with STEMI in a real world setting between 2000 and 2010.

Methods

We evaluated time-dependent changes in the clinical characteristics, management strategies, and one year all-cause mortality of STEMI patients who were enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) between 2000 and 2010, categorized as smokers (n = 2399) and non-smokers (n = 3069). We divided the survey periods into early (2000–2004) and late (2006–2010). The primary endpoint of the study was the occurrence of one-year all-cause mortality.

Results

A total of 4564 STEMI patients were enrolled in the study. Compared with non-smokers, smokers were significantly younger and displayed a significantly lower rate of all-cause mortality at 30 days and 1-year. Both smokers and non-smokers who were enrolled in the late survey period received more evidence-based therapies (primary PCI and guideline-based medications) (p < 0.001 for all). There was a significant reduction in the risk of 1-year all-cause mortality only among non-smokers (HR = 0.664 CI 95% 0.52–0.85, p = 0.0009), whereas smokers who were enrolled in more recent survey periods did not display a significant risk reduction (HR = 1.08 CI 95% 0.77–1.51, p = 0.67).

Conclusion

Survival following STEMI among smokers has not improved over the past decade despite corresponding changes in management strategies. Future trials should focus on reducing the risk in smokers.     

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.     

Associations of mid-regional pro-adrenomedullin levels to cardiovascular and metabolic abnormalities,and mortality in an elderly population from the community

Background

The mid-regional part of the prohormone of adrenomedullin (MR-proADM) is emerging as a novel risk indicator in patients with cardiac disease. We investigated MR-proADM levels and their changes over 5 years in elderly community-dwellers, together with the underlying cardiovascular and metabolic conditions, and the prognostic implications of these measurements.

Methods and results

MR-proADM was analyzed using a sandwich immunoassay (Thermo Fisher Scientific) in participants from the PIVUS study. Measurements were performed at 70 (n = 1002) and 75 years of age (n = 795) together with various measurements of other markers of cardiovascular function. In cross-sectional analyses, MR-proADM was independently related to current smoking, renal dysfunction, obesity, lower left-ventricular ejection fraction, and higher levels of N-terminal pro-B-type natriuretic peptide and C-reactive protein. There were no independent associations to other cardiovascular risk factors or vascular pathologies. MR-proADM levels predicted all-cause mortality during 8.0 years of follow-up independent of cardiovascular risk indicators (adjusted HR 5.1 [95% CI 2.8–9.5]; p < 0.001) using results obtained at 70 and 75 years as updated covariates. Baseline MR-proADM levels improved prognostic discrimination (IDI = 0.018 [p = 0.001]). Also the change in MR-proADM levels over time independently predicted all-cause mortality occurring after 75 years (adjusted HR 13.4 [95% CI 3.5–50.5]; p < 0.001).

Conclusions

MR-proADM levels in the elderly integrate information on several relevant aspects in cardiovascular disease, namely cardiovascular risk factors including obesity, low-grade inflammation, renal dysfunction and left-ventricular abnormalities. Furthermore, MR-proADM and its changes over time predicted mortality, and might provide utility as an indicator of the overall cardiovascular risk burden.     

Ascending aorta elasticity in children with isolated bicuspid aortic valve

Background

Aortic dilation is common in children with bicuspid aortic valve (BAV) but aortic complications are infrequent. The aim of this study was to investigate elastic properties of the ascending aorta (AAo) and its relation to AAo size in children with isolated BAV without significant valve dysfunction.

Methods

24 children with isolated BAV and 24 healthy controls with tricuspid aortic valve (TAV) matched by gender, age and body surface area (BSA) were studied. Aortic strain (AS), aortic distensibility (DIS) and aortic stiffness index (SI) were derived from M-mode echocardiography at the AAo together with cuff blood pressure recordings. BAV children with dilated AAo (z score ≥ 2) and non dilated (z score < 2) were compared.

Results

BAV children had larger aortas than controls at the sinuses of Valsalva, sinotubular junction and AAo (p < 0.05). AS was lower in BAV than in controls (10.15 ± 4.93 vs 16.93 ± 5.17 p = 0.000), DIS was lower in BAV than in controls (8.51 ± 3.90 vs 14.37 ± 4.20 p = 0.000) and SI was higher in BAV than in controls (7.19 ± 4.45 vs 4.05 ± 2.33 p = 0.04). There were no significant differences in AS, DIS and SI between children with dilated and non-dilated AAo. AS, DIS and SI were not related to BSA, age or AAo size.

Conclusions

AAo elasticity assessed by transthoracic echocardiography is impaired in BAV children without significant valve dysfunction compared to TAV children. Impaired elasticity seems to be independent from aortic dilation. Measuring aortic elasticity may help to identify children at greater risk for complications as adults.     

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease

Background

Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients.

Methods

The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD.

Results

CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p < 0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p < 0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p = 0.006). Furthermore, PWV was associated with serum OPG levels (r = 0.19, p < 0.001) and with serum logOPN levels (r = 0.10, p = 0.049). Multivariate linear regression analysis revealed that increased OPG (p = 0.013) and logOPN (p = 0.006) levels are associated with 3‐vessel CAD and Gensini score (p = 0.04 for OPG and p = 0.09 for OPN), independently of other known cardiovascular risk factors.

Conclusion

The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.