Relationship between ablation index and myocardial biomarkers after radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Further in-vivo evidence is needed to support the usefulness of ablation index (AI) in guiding atrial fibrillation (AF) ablation. We aimed at evaluating the relationship between AI and other lesion indicators and the release of myocardial-specific biomarkers following radiofrequency AF ablation. METHODS: Forty-six patients underwent a first-time radiofrequency AF ablation and were prospectively enrolled in this study. Pulmonary vein isolation was performed by six experienced electrophysiologists with a point-by-point approach, guided by strict Visitag criteria and consistent AI target values. Myocardial-specific biomarkers troponin T and creatine kinase myocardial band were measured after 6 (TnT6 and CKMB6) and 20 h (TnT20 and CKMB20) following sheath removal. Ablation duration, impedance drop (ID), force-time integral (FTI) and AI were registered automatically and analyzed offline. RESULTS: TnT release was 985 ± 495 ng/L and 1038 ± 461 ng/L (p = ns) while CKMB release was 7.3 ± 2.7 µg/L and 6.5 ± 2.1 µg/L (p < 0.001) at 6 and 20 h respectively. Ablation duration, ID, FTI and AI were all significantly correlated with the release of myocardial-specific biomarkers both at 6 and 20 h. Ablation index showed the highest degree of correlation with TnT6, TnT20, CKMB6 and CKMB20 (Pearson's R 0.69, 0.69, 0.61, 0.64 respectively, p < 0.001). Multiple regression analysis demonstrated that AI had the strongest association with TnT6, TnT20, CKMB6 and CKMB20 (ß 0.43, ß 0.71, ß 0.44 and ß 0.43 respectively). CONCLUSION: Ablation index appears as the strongest lesion indicator as measured by the release of myocardial-specific biomarkers following radiofrequency catheter ablation for AF.

Elevated CK-MB levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study.

Aim: Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP. Methods: This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables. Results: A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients. Conclusion: CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP.

The combination of creatine kinase-myocardial band isoenzyme and point-of-care cardiac troponin/ contemporary cardiac troponin for the early diagnosis of acute myocardial infarction.

BACKGROUND: The early diagnosis of acute myocardial infarction (AMI) remains challenging, especially for institutions without the high-sensitive cardiac troponin (hs-cTn) assay. Herein, we aim to assess the value of creatine kinase-myocardial band isoenzyme (CK-MB) combined with different cardiac troponin (cTn) assays in AMI diagnosis. METHODS: This multicenter, observational study included 3,706 patients with acute chest pain from September 1, 2015, to September 30, 2017. We classified the participants into three groups according to the cTn assays: the point-of-care cTn (POC-cTn) group, the contemporary cTn (c-cTn) group, and hs-cTn group. The diagnostic value was quantified using sensitivity and the area under the curve (AUC). RESULTS: Compared to the single POC-cTn/c-cTn assays, combining CK-MB and POC-cTn/c-cTn increased the diagnostic sensitivity of AMI (56.1% vs. 63.9%, P<0.001; 82.7% vs. 84.3%, P=0.025). In contrast, combining CK-MB and hs-cTn did not change the sensitivity compared with hs-cTn alone (95.0% vs. 95.0%, P>0.999). In the subgroup analysis, the sensitivity of combining CK-MB and c-cTn increased with time from symptom onset <6 h compared with c-cTn alone (72.8% vs. 75.0%, P=0.046), while the sensitivity did not increase with time from symptom onset >6 h (97.5% vs. 98.3%, P=0.317). The AUC of the combination of CK-MB and POC-cTn significantly increased compared to the single POC-cTn assay (0.776 vs. 0.750, P=0.002). The AUC of the combined CK-MB and c-cTn/hs-cTn assays did not significantly decrease compared with that of the single c-cTn/hs-cTn assays within 6 h. CONCLUSIONS: The combination of CK-MB and POC-cTn or c-cTn may be valuable for the early diagnosis of AMI, especially when hs-cTn is not available.

Sex-specific added value of cardiac biomarkers for 10-year cardiovascular risk prediction.

AIMS: To evaluate the sex-specific predictive value of N-terminal pro B-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase myocardial band (CK-MB) for 10-year risk prediction of coronary heart disease (CHD), stroke, heart failure (HF) and composite outcomes. METHODS: Five-thousand four-hundred thirty individuals (mean age 68.6 years, 59.9% women) from the Rotterdam Study, with biomarker measurements between 1997 and 2001, were included. Participants were followed until 2015. We fitted 'basic' models using traditional cardiovascular risk factors. Improvements in c-statistics and net reclassification improvement (NRI) for events and non-events were calculated. RESULTS: During a median follow-up of 14 years, 747 (13.8%), 563 (10.4%), and 664 (12.2%) participants were diagnosed with CHD, stroke, and HF, respectively. NT-proBNP improved the discriminative performance of the 'basic' model for all endpoints (c-statistic improvements ranging from 0.007 to 0.050) and provided significant event-NRI for HF (14.3% in women; 10.7% in men) and for stroke in men (9.3%). The addition of hs-cTnT increased c-statistic for CHD in women by 0.029 (95% CI, 0.011-0.047) and for HF in men by 0.034 (95% CI, 0.014-0.053), and provided significant event-NRI for CHD (10.3%) and HF (7.8%) in women, and for stroke (8.4%) in men. The added predictive value of CK-MB was limited. CONCLUSION: NT-proBNP and hs-cTnT provided added predictive value for various cardiovascular outcomes above traditional risk factors. Sex differences were observed in the predictive performance of these biomarkers.

Cardiotoxicity of Chemical Substances: An Emerging Hazard Class.

(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria.

Early systolic lengthening by speckle tracking echocardiography predicts outcome after coronary artery bypass surgery.

BACKGROUND: Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, has been linked to loss of myocardial viability and contractile dysfunction. We assessed the long-term prognostic potential of ESL in coronary artery bypass graft (CABG) patients. METHODS: We retrospectively included patients (n = 709; mean age 68 years; 85% men) who underwent speckle tracking echocardiography (median 15 days) prior to CABG. Endpoints were cardiovascular death (CVD) and all-cause mortality. We assessed amplitude of ESL (%), defined as peak positive strain, and duration of ESL (ms), determined as time from Q-wave on the ECG to peak positive strain. We applied Cox models adjusted for clinical risk assessed as EuroSCORE II. RESULTS: During median follow-up of 3.8 years [IQR 2.7-4.9 years], 45 (6%) experienced CVD and 80 (11%) died. In survival analyses adjusted for EuroSCORE II, each 1% increase in amplitude of ESL was associated with CVD (HR 1.35 [95%CI 1.09-1.68], P = 0.006) and all-cause mortality (HR 1.29 [95%CI 1.08-1.54], P = 0.004). Similar findings applied to duration of ESL (per 10ms increase) and CVD (HR 1.12 [95%CI 1.02-1.23], P = 0.016) and all-cause mortality (HR 1.09 [95%CI 1.01--1.17], P = 0.031). The prognostic value of ESL amplitude was modified by sex (P interaction < 0.05), such that the prognostic value was greater in women for both endpoints. When adding ESL duration to EuroSCORE II, the net reclassification index improved significantly for both CVD and all-cause mortality. CONCLUSIONS: Assessment of ESL provides independent and incremental prognostic information in addition to the EuroSCORE II for CVD and all-cause mortality in CABG patients.

Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction.

In patients with a first anterior ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, iron deficiency (ID) was associated with larger infarcts, more extensive microvascular obstruction, and higher frequency of adverse left ventricular remodeling as assessed by cardiac magnetic resonance imaging. In mice, an ID diet reduced the activity of the endothelial nitric oxide synthase/soluble guanylate cyclase/protein kinase G pathway in association with oxidative/nitrosative stress and increased infarct size after transient coronary occlusion. Iron supplementation or administration of an sGC activator before ischemia prevented the effects of the ID diet in mice. Not only iron excess, but also ID, may have deleterious effects in the setting of ischemia and reperfusion.

Performance of Copeptin for Early Diagnosis of Acute Myocardial Infarction in an Emergency Department Setting.

BACKGROUND: Rapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI). METHODS: We prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed. RESULTS: The patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P=0.022, ≤1 hour; STEMI: P=0.017, ≤1 hour and P=0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients. CONCLUSIONS: The combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting.

Evolution of Immune Checkpoint Blockade-Induced Myocarditis Over 2 Years.

Ipilimumab and nivolumab for melanoma induced smoldering myocarditis remitting with steroids. Rechallenge with nivolumab produced steroid-refractory myocarditis confirmed by electron microscopy. Tacrolimus and mycophenolate transiently reduced inflammation, but antithymocyte globulin induced remission. Cardiomyopathy with fatty infiltration ensued, but the patient succumbed to rampant melanoma progression after lymphocyte depletion. (Level of Difficulty: Advanced.).

Coronavirus disease 2019 and cardiovascular system: A narrative review.

At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.

Clinical and Functional Outcomes Associated With Myocardial Injury After Transfemoral and Transapical Transcatheter Aortic Valve Replacement: A Subanalysis From the PARTNER Trial (Placement of Aortic Transcatheter Valves).

OBJECTIVES: This study sought to clarify the clinical and echocardiographic prognostic implication of myocardial injury after transcatheter aortic valve replacement (TAVR). BACKGROUND: The clinical significance of cardiac biomarker elevation after TAVR remains unclear. METHODS: Patients treated with TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial were divided into tertiles (T1, T2, T3) based on the difference between the values on post-procedure day 1 and the baseline values of 2 cardiac biomarkers: cardiac troponin I (ΔcTnI); and creatine kinase-myocardial band (ΔCK-MB) fraction. Patients were stratified according to their access route: transfemoral (TF) (n = 1,840) or transapical (TA) (n = 1,173). RESULTS: At 30 days after TF-TAVR, patients in the highest tertile (T3) of cardiac biomarker elevation had a higher rate of all-cause mortality (ΔcTnI: T3: 5.4% vs. T1: 0.5%, p = 0.006; ΔCK-MB: T3: 5.7% vs. T1: 0.9%, p = 0.006) and cardiovascular mortality (ΔcTnI: T3: 4.9% vs. T1: 0.5%, p = 0.01; ΔCK-MB: T3: 3.9% vs. T1: 0.5%, p = 0.02). At 1 year, only patients in the highest CK-MB tertile had higher rates of all-cause (25.4% vs. 16.8%, p = 0.02) and cardiovascular (10.3% vs. 5.0%) mortality. Multivariable analysis demonstrated that greater release of cardiac biomarkers was independently associated with increased mortality in the TF population. After TA-TAVR, being in the highest tertile of cardiac biomarker elevation had no influence on clinical and echocardiographic outcomes at 30 days and 1 year. CONCLUSIONS: After TF-TAVR, a greater degree of myocardial injury was associated with higher rates of 30-day all-cause and cardiovascular mortality. At 1 year, being in the highest tertile of ΔCK-MB was correlated with a higher rate of all-cause and cardiac mortality. Finally, the level of myocardial injury after TA-TAVR had no impact on clinical and echocardiographic outcomes.

Clinical validation of coronary artery flow through an intracoronary shunt during off-pump coronary artery bypass grafting.

OBJECTIVES: Intracoronary shunts have been developed for a bloodless field and preserved forward flow preventing ischemia during off-pump coronary artery bypass (OPCAB) surgery. However, reports directly measuring the forward flow through the shunt in clinical settings are lacking. METHODS: Using a 7.5-MHz Doppler probe, we investigated the coronary flow through a 1.5-mm shunt inserted into the left anterior descending artery (LAD) for anastomosis with the internal thoracic artery during OPCAB in 30 consecutive patients. The following Doppler flow parameters were obtained before and after shunting: peak velocity, mean velocity, time-velocity integral, and flow. RESULTS: No patients developed significant electrocardiographic changes and the peak value of postoperative myocardial band of creatine kinase was 17 ± 16 IU/L. All Doppler flow parameters of the LAD decreased significantly after shunting; peal velocity: 71.3 ± 34.6 cm/second to 54.5 ± 25.3 cm/second (-24% ± 27%), mean velocity: 33.3 ± 18.3 cm/second to 26.3 ± 14.0 cm/second (-21% ± 23%), and time-velocity integral: 28.7 ± 12.1 cm to 19.0 ± 7.1 cm (-28% ± 14%), and flow: 38.7 ± 16.8 mL/minute to 25.0 ± 9.5 mL/minute (-31% ± 13%) (P < .01). CONCLUSIONS: The LAD flow is preserved at least 50% through a 1.5-mm intracoronary shunt, although the flow pattern was attenuated, during OPCAB anastomosis. The Doppler evaluation of the coronary artery flow before and after shunting is useful to justify the protective use of the shunt on myocardial perfusion during OPCAB.

Periprocedural myocardial injury in chronic total occlusion percutaneous interventions: a systematic cardiac biomarker evaluation study.

OBJECTIVES: This study sought to evaluate the incidence, correlates, and clinical implications of periprocedural myocardial injury (PMI) during percutaneous coronary intervention (PCI) of chronic total occlusions (CTO). BACKGROUND: The risk of PMI during CTO PCI may be underestimated because systematic cardiac biomarker measurement was not performed in published studies. METHODS: We retrospectively examined PMI among 325 consecutive CTO PCI performed at our institution between 2005 and 2012. Creatine kinase-myocardial band fraction and troponin were measured before PCI and 8 to 12 h and 18 to 24 h after PCI in all patients. PMI was defined as creatine kinase-myocardial band increase ≥ 3 x the upper limit of normal. Major adverse cardiac events during mid-term follow-up were evaluated. RESULTS: Mean age was 64 ± 8 years. The retrograde approach was used in 26.8% of all procedures. The technical and procedural success was 77.8% and 76.6%, respectively. PMI occurred in 28 patients (8.6%, 95% confidence intervals: 5.8% to 12.2%), with symptomatic ischemia in 7 of those patients. The incidence of PMI was higher in patients treated with the retrograde than the antegrade approach (13.8% vs. 6.7%, p = 0.04). During a median follow-up of 2.3 years, compared with patients without PMI, those with PMI had a higher incidence of major adverse cardiac events (hazard ratio [HR]: 2.25, p = 0.006). Patients with only asymptomatic PMI also had a higher incidence of major adverse cardiac events on follow-up (HR: 2.26, p = 0.013). CONCLUSIONS: Systematic measurement of cardiac biomarkers post-CTO PCI demonstrates that PMI occurs in 8.6% of patients, is more common with the retrograde approach, and is associated with worse subsequent clinical outcomes during mid-term follow-up.

Two-year outcomes after first- or second-generation drug-eluting or bare-metal stent implantation in all-comer patients undergoing percutaneous coronary intervention: a pre-specified analysis from the PRODIGY study (PROlonging Dual Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY).

OBJECTIVES: This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention. BACKGROUND: Few studies have directly compared second-generation drug-eluting stents with each other or with BMS. METHODS: We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint. RESULTS: Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001). CONCLUSIONS: Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).

OBJECTIVES: This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. BACKGROUND: Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. METHODS: Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. RESULTS: In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. CONCLUSIONS: Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).

Influence of racing on the serum concentrations of the cardiac biomarkers troponin I and creatine kinase myocardial band (CK-MB) in racing greyhounds.

The objective of this study was to investigate the effect of racing on the serum concentrations of cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB) in 32 racing greyhounds. Blood samples were collected 24h prior to a 7 km race (T0), within 2h of completion of the race (T1), and 24h post-race (T2). Blood samples were also collected from 20 non-racing greyhounds. The median cTnI concentration in the racing greyhounds was not significantly different from that in the non-racing greyhounds (0.045 ng/mL). Before racing, the median cTnI concentration in the racing greyhounds was 0.050 ng/mL. Following the 7 km race, 31/32 greyhounds showed increases in cTnI concentrations which were significantly higher than the pre-race concentrations (P<0.0001). cTnI concentrations dropped back 24h post-race to values not significantly different from the pre-race concentrations. Following the race, 5/32 greyhounds showed mild increases in CK-MB concentrations but these were not significantly different from the pre-race values. These findings could be of importance when evaluating greyhounds with suspected cardiac disease that have recently performed hard exercise.

Impact of attenuated plaque as detected by intravascular ultrasound on the occurrence of microvascular obstruction after percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: The aim of the study was to investigate whether intravascular ultrasound (IVUS) can predict microvascular obstruction (MVO) as detected by magnetic resonance imaging (MRI) after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: MVO occurs in a sizable proportion of patients with acute myocardial infarction despite successful PCI and results in poor clinical outcomes. METHODS: We assessed infarct-related lesions in 68 patients with STEMI by using IVUS before primary PCI. All patients were examined by MRI 1 week after primary PCI. RESULTS: MRI-derived MVO was seen in 23 patients (34%). In the IVUS assessment, the frequency of plaque rupture, echolucent plaque, calcification and positive remodeling, and quantitative geometric data were not different between the MVO group and the no-MVO group. Although the frequency of plaque with ultrasound attenuation was similar between the 2 groups (87% vs. 89%, p = 0.999), the maximum attenuation angle (280° [range: 215° to 360°] vs. 150° [range: 95° to 300°], p = 0.008) and attenuation length (11.3 mm [range: 7.2 to 17.8 mm] vs. 6.8 mm [range: 3.0 to 10.4 mm], p = 0.009) were significantly greater in the MVO group than the no-MVO group. Multivariable logistic regression analysis showed that attenuated plaque with a maximum attenuation angle of >180° and attenuation length of >5 mm was an independent predictor of MVO (odds ratio: 6.07, 95% confidence interval: 1.89 to 19.53, p = 0.002). CONCLUSIONS: Attenuated plaque with maximum attenuation angle of >180° and attenuation length of >5 mm was associated with the occurrence of MVO after primary PCI. IVUS might to be a useful tool for risk stratification in STEMI patients undergoing primary PCI.

Prognostic value of microvascular resistance index immediately after primary percutaneous coronary intervention on left ventricular remodeling in patients with reperfused anterior acute ST-segment elevation myocardial infarction.

OBJECTIVES: This study sought to investigate the relationship between the degree of microvascular dysfunction assessed by a dual-sensor guidewire (pressure and Doppler velocity) and left ventricular (LV) remodeling after successful primary percutaneous coronary intervention (PPCI) for a first anterior acute myocardial infarction (AMI). BACKGROUND: Microvascular dysfunction after AMI is associated with progressive LV dilation. METHODS: In 24 consecutive patients, the microvascular resistance index (MVRI) immediately after PPCI was calculated as the ratio of the mean distal pressure to average peak flow velocity during maximal hyperemia. Cardiac magnetic resonance was performed to determine LV volumes at baseline and 8-month follow-up. LV remodeling was defined as an increase in left ventricular end-diastolic volume (LVEDV) of ≥20%. RESULTS: In patients with an MVRI greater than the median value of 2.96 mm Hg·cm(-1)·s, the LVEDV increased significantly from 117.1 ± 20.7 ml at baseline to 146.5 ± 21.4 ml (p = 0.006) at 8 months, whereas it did not change between baseline and 8 months (108.2 ± 21.2 ml vs. 111.6 ± 29.9 ml, p = 0.620) in patients with an MVRI ≤2.96 mm Hg·cm(-1)·s. LV remodeling was more frequent in the group with an MVRI >2.96 mm Hg·cm(-1)·s (64% vs. 15%, p = 0.033). Furthermore, there was a positive correlation between MVRI and the percentage of increase or decrease in LVEDV (r = 0.42, p = 0.042). Logistic regression analysis showed that MVRI was the strongest univariate predictor of LV remodeling. The best cutoff value of MVRI was 2.96 mm Hg·cm(-1)·s with a sensitivity of 78% and a specificity of 73%. CONCLUSIONS: MVRI immediately after PPCI predicts LV remodeling in patients with reperfused anterior AMI.

Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial.

OBJECTIVES: This study sought to evaluate whether remote ischemic post-conditioning (RIPC) could reduce enzymatic infarct size in patients with anterior ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND: Myocardial reperfusion injury may attenuate the benefit of pPCI. In animal models, RIPC mitigates myocardial reperfusion injury. METHODS: One hundred patients with anterior ST-segment elevation myocardial infarction and occluded left anterior descending artery were randomized to pPCI + RIPC (n = 50) or conventional pPCI (n = 50). RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb. The primary endpoint was infarct size assessed by the area under the curve of creatinine kinase-myocardial band release (CK-MB). Secondary endpoints included the following: infarct size assessed by cardiac magnetic resonance delayed enhancement volume; T2-weighted edema volume; ST-segment resolution >50%; TIMI (Thrombolysis In Myocardial Infarction) frame count; and myocardial blush grading. RESULTS: Four patients (2 RIPC, 2 controls) were excluded due to missing samples of CK-MB. A total of 96 patients were analyzed; median area under the curve CK-MB was 8,814 (interquartile range [IQR]: 5,567 to 11,325) arbitrary units in the RIPC group and 10,065 (IQR: 7,465 to 14,004) arbitrary units in control subjects (relative reduction: 20%, 95% confidence interval: 0.2% to 28.7%; p = 0.043). Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after randomization, and 66 patients repeated a second scan after 4 months. T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects (p = 0.049). ST-segment resolution >50% was 66% in RIPC and 37% in control subjects (p = 0.015). We observed no significant differences in TIMI frame count, myocardial blush grading, and delayed enhancement volume. CONCLUSIONS: In patients with anterior ST-segment elevation myocardial infarction, RIPC at the time of pPCI reduced enzymatic infarct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution >50%. (Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention [PCI] [RemPostCon]; NCT00865722).

Sivelestat attenuates lung injury in surgery for congenital heart disease with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension associated with congenital heart disease increases the risk of surgery using cardiopulmonary bypass. Sivelestat is a neutrophil elastase inhibitor thought to have a prophylactic effect against lung injury after surgery using bypass. We elucidated that Sivelestat had the protective effect on lung in patients with congenital heart disease and pulmonary hypertension who underwent surgery using bypass. METHODS: This study was a controlled prospective randomized trial and enrolled 13 neonates or infants with ventricular septal defect and pulmonary hypertension. The patients were assigned to either sivelestat with the dose of 0.2 mg/kg per hour (sivelestat group, n = 7) or saline (placebo group, n = 6) from the start of bypass until 6 hours after bypass. Proinflammatory cytokines and adhesion molecules on leukocytes were measured at 10 time points during the above period. Pulmonary function was assessed perioperatively. RESULTS: Compared with the placebo group, the sivelestat group had significantly lower values of alveolar-arterial oxygen tension gradient at 24 hours (p = 0.038) and at 48 hours (p = 0.028) after bypass, and significantly better balance of hydration at 48 hours after bypass (p = 0.012). The sivelestat group also showed significantly lower plasma levels of interleukin-8 immediately after bypass (p = 0.041) and interleukin-10 at 15 minutes after removal of the aortic cross-clamp (p = 0.048), and immediately after bypass (p = 0.037). CONCLUSIONS: Administration of sivelestat during bypass prevented pulmonary damage and activities of proinflammatory cytokines at the cardiac operation in neonates or infants. Our results show that sivelestat may be considered to protect pulmonary function against the injury by bypass.