Outcomes After Early Postoperative Myocardial Infarction Due to Graft Failure in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Early graft failure (EGF) after coronary artery bypass grafting (CABG) occurs in up to 12% of grafts, but is often clinically unapparent. EGF may result in perioperative myocardial infarction with consequently increased mortality. The aim of the present study was to analyze the incidence of clinically apparent EGF in patients undergoing CABG and the influence on mortality. METHODS: We analyzed outcomes of consecutive patients undergoing CABG from January 2015 to December 2018 with respect to postoperative emergency coronary angiography (CAG) due to suspected EGF and 30-day mortality. Patients with CAG-documented EGF were matched to patients without EGF to examine predictors of mortality. RESULTS: The analysis included 5638 patients undergoing CABG. Eighty-six patients (1.5%) underwent emergency CAG due to suspected EGF. Clinically apparent EGF was observed in 61 of these patients (70.9%), whereas 14 (16.3%) had a culprit lesion in a native coronary artery. The majority of patients (n = 45; 52.3%) were treated with percutaneous coronary intervention and 31 (36%) underwent re-do CABG. The remaining patients were treated conservatively. The 30-day mortality rate of suspected EGF patients undergoing CAG was 22.4% (n = 19), which was higher than the mortality rate of 2.8% overall (P<.001); this remained higher after matching the EGF patients with the control group (11 [20.4%] vs 2 [4.0%]; P=.02). CONCLUSION: Emergency CAG after CABG is rare and is primarily carried out in patients with EGF. The 30-day mortality rate of these patients is high, and EGF is an independent predictor of mortality. Perioperative CAG with subsequent treatment is mandatory in these patients.

First case report of fully robotically assisted lithotripsy in heavily calcified left main stenosis.

Background: Percutaneous coronary intervention (PCI) is the standard-of-care treatment for left main stenosis as an alternative to bypass surgery. In addition, severe coronary lesion calcification can be modified by intravascular lithotripsy (IVL). However, with PCI and debulking treatment options, there are inherent limitations. PCI poses an increased health burden for the treating physician that is associated with wearing a heavy, lead-lined apron and being exposed to radiation. To overcome these issues, a robotically assisted angioplasty system (rPCI) was established that enables the operator to perform PCI remotely in routine clinical procedures. Furthermore, IVL have not been used remotely. Case summary: Here, we report the use of this technique for treating a heavily calcified left main stenosis in an 82-year-old male with previously diagnosed two-vessel coronary artery disease, progressive symptoms of dyspnoea at high cardio-vascular risk profile. The decision of the local heart team declined surgery. To the best of our knowledge, this is the first report of successful rPCI combined with IVL. Discussion: In the case presented, rPCI was feasible and safe even in a complex lesion of the left main coronary artery requiring IVL. rPCI is a revolutionary new technique that may be applied to various types of coronary artery lesions.

Normative values of non-invasively assessed RV function and pulmonary circulation coupling for pre-participation screening derived from 497 male elite athletes.

BACKGROUND: Reference values for right ventricular function and pulmonary circulation coupling were recently established for the general population. However, normative values for elite athletes are missing, even though exercise-related right ventricular enlargement is frequent in competitive athletes. METHODS: We examined 497 healthy male elite athletes (age 26.1 ± 5.2 years) of mixed sports with a standardized transthoracic echocardiographic examination. Tricuspid annular plane excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) were measured. Pulmonary circulation coupling was calculated as TAPSE/SPAP ratio. Two age groups were defined (18-29 years and 30-39 years) and associations of clinical parameters with the TAPSE/SPAP ratio were determined and compared for each group. RESULTS: Athletes aged 18-29 (n = 349, 23.8 ± 3.5 years) displayed a significantly lower TAPSE/SPAP ratio (1.23 ± 0.3 vs. 1.31 ± 0.33 mm/mmHg, p = 0.039), TAPSE/SPAP to body surface area (BSA) ratio (0.56 ± 0.14 vs. 0.6 ± 0.16 mm*m2/mmHg, p = 0.017), diastolic blood pressure (75.6 ± 7.9 vs. 78.8 ± 10.7 mmHg, p < 0.001), septal wall thickness (10.2 ± 1.1 vs. 10.7 ± 1.1 mm, p = 0.013) and left atrial volume index (27.5 ± 4.5 vs. 30.8 ± 4.1 ml/m2, p < 0.001), but a higher SPAP (24.2 ± 4.5 vs. 23.2 ± 4.4 mmHg, p = 0.035) compared to athletes aged 30-39 (n = 148, 33.1 ± 3.4 years). TAPSE was not different between the age groups. The TAPSE/SPAP ratio was positively correlated with left ventricular stroke volume (r = 0.133, p = 0.018) and training amount per week (r = 0.154, p = 0.001) and negatively correlated with E/E' lat. (r = -0.152, p = 0.005). CONCLUSION: The reference values for pulmonary circulation coupling determined in this study could be used to interpret and distinguish physiological from pathological cardiac remodeling in male elite athletes.

[Main stem intervention-Is one stent better than two after all?] / Hauptstammintervention ­ Ist ein Stent doch besser als zwei?

The current European Society of Cardiology (ESC) guideline recommendations give equal consideration to percutaneous coronary interventions (PCI) and bypass surgery for the treatment of main stem stenosis. Because of the anatomical setting, interventional treatment of main stem stenosis represents a complex PCI procedure. For this reason, extensive planning of the PCI with the use of intravascular imaging is necessary to assess the extent of calcification in the main stem itself and also in the proximal vascular segment of the anterior interventricular branch (left anterior descending, LAD) and the circumflex branch (RCX). Furthermore, an assessment of the vessel diameter is necessary for planning the PCI as well as for stent selection. Especially in the case of severely calcified lesions, careful and routine dissection of the lesion to be treated is essential. For this purpose, so-called cutting balloons, scoring balloons or debulking devices (rotational atherectomy, orbital atherectomy) can be used. In the case of a main stem stenosis involving the bifurcation, the choice of stent strategy depends on the extent of calcification of the daughter vessels (LAD and RCX), as well as the complexity of the bifurcation stenosis. The superiority of the so-called double kissing (DK) crush technique over a single stent strategy could be confirmed in a randomized trial and should be used in main stem bifurcation stenoses with pronounced calcification of the proximal segments of the LAD and RCX (stenosis length > 10 mm, and > 70% diameter stenosis). The already established 2­stent strategies for the treatment of bifurcation stenosis could be modified or further developed. In preliminary studies the advantage of the so-called DK nano-crush technique and the DK culotte technique could be shown, whereby these initial results still have to be confirmed by larger randomized studies.

Latest Developments in Robotic Percutaneous Coronary Intervention.

Interventional cardiovascular medicine has seen constant progress over the last few decades. Since the first angiograms and percutaneous transluminal coronary angioplasty were carried out, this progress has been tremendous and has led to a substantial decline in cardiovascular morbidity and mortality. The purpose of this article is to report and review the latest developments and evidence in robotics-assisted percutaneous coronary intervention (rPCI) and its potential future applications, opportunities, and limitations. Contemporary evidence shows that rPCI can lead to a significant reduction in radiation exposure as well as medical hazards for cardiologists. Rates of device and procedural success remain high and there is no evidence of a disadvantage for the patient. The accuracy of implantation with a reduced geographic mismatch is a further advantage that can result in a higher quality of treatment. Even in complex coronary lesions and procedures, rPCI seems to be safe and efficient. The latest developments include telestenting over hundreds of kilometers from a remote platform. Currently, the main limitations are the absence of large-scale randomized trials for the valid assessment of the benefits and disadvantages of rPCI as well as the technical limitations of the currently available rPCI systems. rPCI is a forward-looking innovation in cardiology that is applicable to a wide range of coronary interventions. Despite the present lack of knowledge and the limited data concerning the outcome for the patient, the available literature reveals promising results that should lead to improvements for physicians and patients.

Definition of acute kidney injury impacts prevalence and prognosis in ACS patients undergoing coronary angiography.

BACKGROUND: Development of acute kidney injury (AKI) in invasively managed patients with acute coronary syndrome (ACS) is associated with a markedly increased mortality risk. Different definitions of AKI are in use, leading to varying prevalence and outcome measurements. The aim of the present study is to analyze an ACS population undergoing coronary angiography for differences in AKI prevalence and outcome using four established AKI definitions. METHODS: 944 patients (30% female) were enrolled in a prospective registry between 2003 and 2005 with 6-month all-cause mortality as outcome measure. Four established AKI definitions were used: an increase in serum creatinine (sCR) ≥ 1.5 fold, ≥ 0.3 mg/dl, and ≥ 0.5 mg/dl and a decrease in eGFR > 25% from baseline (AKIN 1, AKIN 2, CIN, and RIFLE definition groups, respectively). RESULTS: AKI rates varied widely between the different groups. Using the CIN definition, AKI frequency was lowest (4.4%), whereas it was highest if the RIFLE definition was applied (13.2%). AKIN 2 displayed a twofold higher AKI prevalence compared with AKIN 1 (10.2% vs. 5.3% (p < 0.001)). AKI was a strong risk factor for mid-term mortality, with distinctive variability between the definitions. The lowest mortality risk was found in the RIFLE group (HR 6.0; 95% CI 3.7-10.0; p < 0.001), whereas CIN revealed the highest risk (HR 16.7; 95% CI 9.9-28.1; p < 0.001). CONCLUSION: Prevalence and outcome in ACS patients varied considerably depending on the AKI definition applied. To define patients with highest renal function-associated mortality risk, use of the CIN definition seems to have the highest prognostic relevance.

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension.

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001) and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in receiver operating characteristic analysis (area under the curve (AUC) 0.79). There was no significant difference between the AUCs of CILP1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) (AUC 0.82). High CILP1 (cut-off value for maladaptive RV of ≥4373 pg·mL-1) was associated with lower tricuspid annular plane excursion/pulmonary artery systolic pressure ratios (p<0.001) and higher NT-proBNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

Who Is Afraid of CRP? Elevated Preoperative CRP Levels Might Attenuate the Increase in Inflammatory Parameters in Response to Lung Cancer Surgery.

During surgery, ATP from damaged cells induces the release of interleukin-1ß, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1ß, although high CRP levels are deemed to be a poor prognostic marker. Here, we retrospectively investigated if preoperative CRP levels correlate with postoperative CRP, leukocyte counts and fever in the context of anatomical lung resection and systematic lymph node dissection as first line lung cancer therapy. No correlation was found in the overall results. In men, however, preoperative CRP and leukocyte counts positively correlated on postoperative days one to two, and a negative correlation of CRP and fever was seen in women. These correlations were more pronounced in men taking statins and in statin-naïve women. Accordingly, the inhibitory effect of CRP on the ATP-induced interleukin-1ß release was blunted in monocytes from coronary heart disease patients treated with atorvastatin compared to monocytes obtained before medication. Hence, the common notion that elevated CRP levels predict more severe postoperative inflammation should be questioned. We rather hypothesize that in women and statin-naïve patients, high CRP levels attenuate trauma-induced increases in inflammatory markers.

IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation.

Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163-/CD68+) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals.

Risk of perioperative coronary stent stenosis or occlusion in patients with previous percutaneous coronary intervention undergoing coronary artery bypass grafting surgery.

OBJECTIVES: There is an ongoing discussion about how to treat coronary stents during bypass surgery: Should patent stents be left alone and the stented vessels be ungrafted, or should every stented coronary artery receive a bypass graft? This study aims to determine the relevance of perioperative stent stenosis or occlusion on postoperative outcomes up to 3 years postoperatively. METHODS: Patients undergoing coronary artery bypass grafting surgery (CABG) (±concomitant procedures) with previous percutaneous coronary intervention from 4 centres were prospectively included in this observatory study between April 2015 and June 2017. A coronary angiography was conducted between the fifth and seventh postoperative days. The preoperative and postoperative angiograms were assessed in a core laboratory, assessing the patencies of coronary stents and bypass grafts. The core lab investigators were blinded to the patients' characteristics and perioperative course. RESULTS: A total of 107 patients were included in the study. In the postoperative coronary angiography, 265 bypass grafts and 189 coronary stents were examined angiographically. Ninety-seven percent of preoperatively patent stents remained patent. New coronary stent stenoses were observed in 5 patients (4.7%). All 5 patients were asymptomatic and managed conservatively. Bypass stenoses were observed in 12 patients (11%), of whom were managed conservatively, 4 underwent percutaneous coronary intervention and 1 underwent redo-CABG. Two years postoperatively, 97% of patients were alive. Patients with new stent stenosis tended to have a better survival compared with patients with bypass stenosis (100% vs 73%; P = 0.09) up to 3 years postoperatively. CONCLUSIONS: Perioperative coronary stent stenosis occurs rarely. It is safe to leave a patently stented coronary vessel without bypass grafting.

Transvascular transcatheter aortic valve implantation in 2017.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is emerging as the standard of care for patients with severe aortic stenosis. Recent results have been favourable even for patients with low periprocedural risk. METHODS: We analysed the number of procedures, complications, and in-hospital mortality rates of all patients undergoing isolated aortic valve replacement in 2017 in Germany, focussing especially on transvascular (TV) TAVI. Patients were stratified according the German Aortic Valve Score (AKL) into the risk classes low, intermediate, high and very high (≥ 10%). RESULTS: A total of 17,956 TV-TAVI and 9011 isolated surgical aortic valve replacements (iSAVR) were performed in Germany in 2017. Although the total rate of intraprocedural complications after TV-TAVI was the same as in 2016 (both 7.4%), fewer patients experienced an arterial vascular complication in 2017 (2017: 6.0%; 2016: 7.1%; p < 0.001). Likewise, the rate of new pacemaker implantation decreased (2017: 9.6%; 2016:11.4%; p < 0.001). In-hospital mortality after TV-TAVI and iSAVR was equal (2.7%) in 2017, despite the much higher risk profile of TV-TAVI patients. Using the AKL score as reference, TV-TAVI showed a more favourable observed-to-expected mortality (O/E) ratio (0.89) than iSAVR (1.14)- even more pronounced in patients at low risk (0.81 vs. 1.14). CONCLUSIONS: The rates of major complications like bleeding and permanent pacemaker implantation after TV-TAVI keep declining. In 2017 patients undergoing TV-TAVI had a low in-hospital mortality rate with an O/E ratio < 1, indicating that the results were again better than those of all TAVI and SAVR of the previous year. Overall in-hospital mortality after transvascular TAVI and isolated aortic valve repair 2017 in Germany stratified to risk groups by the German Aortic Valve Score (German AV Score/AKL Score): low risk group (AKL 0- < 3%), intermediate risk group (AKL 3- < 6%), high risk group (AKL 6- < 10%) and very high risk group (AKL ≥ 10%).

Incidence and outcome of peri-procedural transcatheter heart valve embolization and migration: the TRAVEL registry (TranscatheteR HeArt Valve EmboLization and Migration).

AIMS: Peri-procedural transcatheter valve embolization and migration (TVEM) is a rare but potentially devastating complication of transcatheter aortic valve implantation (TAVI). We sought to assess the incidence, causes, and outcome of TVEM in a large multicentre cohort. METHODS AND RESULTS: We recorded cases of peri-procedural TVEM in patients undergoing TAVI between January 2010 and December 2017 from 26 international sites. Peri-procedural TVEM occurred in 273/29 636 (0.92%) TAVI cases (age 80.8 ± 7.3 years; 53.8% female), of which 217 were to the ascending aorta and 56 to the left ventricle. The use of self-expanding or first-generation prostheses and presence of a bicuspid aortic valve were independent predictors of TVEM. Bail-out measures included repositioning attempts using snares or miscellaneous tools (41.0%), multiple valve implantations (83.2%), and conversion to surgery (19.0%). Using 1:4-propensity matching, we identified a cohort of 235 patients with TVEM (TVEMPS) and 932 patients without TVEM (non-TVEMPS). In the matched cohort, all-cause mortality was higher in TVEMPS than in non-TVEMPS at 30 days (18.6% vs. 4.9%; P < 0.001) and after 1 year (30.5% vs. 16.6%; P < 0.001). Major stroke was more frequent in TVEMPS at 30 days (10.6% vs. 2.8%; P < 0.001), but not at 1 year (4.6% vs. 1.9%; P = 0.17). The need for emergent cardiopulmonary support, major stroke at 30 days, and acute kidney injury Stages 2 and 3 increased the risk of 1-year mortality, whereas a better renal function at baseline was protective. CONCLUSION: Transcatheter valve embolization and migration occurred in approximately 1% and was associated with increased morbidity and mortality.

Predictive value of preprocedural procalcitonin for short- and long-term mortality after transfemoral transcatheter aortic valve implantation.

Current risk scores used for patients undergoing transcatheter aortic valve implantation (TAVI) do not reliably predict adverse events after TAVI. Procalcitonin (PCT) is associated with increased atherosclerotic burden and adverse outcomes in patients with cardiovascular disease. The aim of our study is to assess the predictive value of preprocedural serum PCT levels in comparison with established risk scores in TAVI patients. A total of 243 patients undergoing transfemoral TAVI at our institution were included prospectively in the study and 230 of these patients participated in the follow-up 1 year after TAVI. The primary endpoints were mortality at 30 days and 1 year. Multivariable analysis revealed that preprocedural PCT was the only independent predictor of 30-day mortality (HR 2.84; 95% CI 1.59-5.06; p < 0.001) and 1-year mortality (HR 1.90; 95% CI 1.17-3.11; p = 0.01), whereas high-sensitivity C-reactive protein showed no association with procedural outcomes. The results of ROC analysis showed good predictive power of PCT for both outcomes (AUC 0.75; p = 0.0003 for 30-day mortality and AUC 0.71; p < 0.0001 for 1-year mortality). An optimal cut-off value for PCT of 0.06 ng/ml for short- and long-term mortality was determined with the Youden index. A significantly higher mortality rate was observed in the high-PCT group (≥ 0.06 ng/ml) based on Kaplan-Meier analysis (log rank = 12.1; p = 0.001 at 30 days and log rank = 14.2; p = 0.0002 at 1 year). Patients in the high-PCT group also had a considerably worse clinical pro6file. In conclusion, preprocedural PCT is an independent predictor of 30-day and 1-year mortality after TAVI. In particular, a cut-off value of 0.06 ng/ml discriminates patients at higher risk of mortality within 30 days and 1 year of TAVI.

Evaluation of cystatin C and neutrophil gelatinase-associated lipocalin as predictors of mortality in patients undergoing percutaneous mitral valve repair (MitraClip).

BACKGROUND: Compromised renal function is a major risk factor that is strongly associated with poor outcome in patients with mitral regurgitation (MR) and heart failure. Cystatin C, a cysteine protease inhibitor, has been used as a specific and sensitive biomarker of renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is another sensitive biomarker that specifically indicates functional and structural kidney damage. The aim of the present study was to determine the predictive value of serum cystatin C and urinary NGAL as indicators of mortality in patients undergoing percutaneous mitral valve repair (PMVR). METHODS: A total of 120 consecutive patients (age: 77.3 years [±11.2]) undergoing PMVR using the MitraClip system were included in this study. Venous blood and urinary samples were collected for biomarker analysis prior to PMVR. Physiological parameters, medication use, safety events, and all-cause mortality were assessed 12 months after the procedure. RESULTS: Twelve months after PMVR, there was a significant reduction in the severity of MR (P < 0.001), and an improvement in the New York Heart Association class (P < 0.01) was documented. Baseline levels of serum cystatin C (nonsurvivors: 2.4 mg/L [interquartile, IQR: 1.7;3.1] vs survivors: 1.7 mg/L [IQR: 1,3;2.1], P < 0.001) and urinary NGAL (nonsurvivors: 242.0 ng/mL [IQR: 154.5;281.5] vs survivors: 132.0 ng/mL [IQR:107.0;177.3], P < 0.001) were significantly higher in patients who died during the 12-month follow-up period. CONCLUSION: Cystatin C and urinary NGAL were found to be predictors of long-term mortality in high-risk patients undergoing PMVR. Thus, cystatin C and NGAL assessment may be helpful in risk stratification in patients undergoing PMVR.

Galectin-3 and ST2 as predictors of therapeutic success in high-risk patients undergoing percutaneous mitral valve repair (MitraClip).

BACKGROUND: Percutaneous mitral valve repair (PMVR) is an interventional treatment option in patients with severe mitral regurgitation (MR) and at high risk for open-heart surgery. Currently, limited information exists about predictors of procedural success after PMVR. Galectin-3 (Gal-3) and suppression of tumorigenicity 2 (ST2) induce fibrotic alterations in severe MR and heart failure. We sought to examine the predictive value of Gal-3 and ST2 as specific indicators of therapeutic success in high-risk patients undergoing PMVR. HYPOTHESIS: We hypothesize that extended cardiac fibrotic alterations might have impact on successful MR reduction after the MitraClip procedure. METHODS: A total of 210 consecutive patients undergoing PMVR using the MitraClip system were included in this study. Procedural success was defined as an immediate reduction of MR by ≥2 grades, assessed by echocardiography. Venous blood samples were collected prior to PMVR and at 6 months follow-up for biomarker analysis. RESULTS: After PMVR there was a significant reduction in the severity of MR (MR grade: 3 ±0.3 vs 1.6 ±0.6, P <0.001). Low baseline Gal-3 levels (PMVRsuccess : 22.0 ng/mL [IQR, 17.3-30.9] vs PMVRfailure : 30.6 ng/mL [IQR, 24.8-42.3], P <0.001) and ST2 levels (PMVRsuccess : 900.0 pg/mL [IQR, 619.5-1114.5] vs PMVRfailure : 1728.0 pg/mL [IQR, 1051.March 1, 1930], P < 0.001) were associated with successful MR reduction after PMVR. Also, ROC analysis identified low baseline Gal-3 and ST2 levels as predictors of therapeutic success after PMVR (AUCGal-3 :0.721 [IQR, 0.64-0.803], P < 0.001; AUCST2 : 0.807 [IQR, 0.741-0.872], P < 0.001). CONCLUSIONS: There was an association between low Gal-3 and ST2 plasma levels and successful MR reduction in patients with severe MR undergoing PMVR using the MitraClip system.

Specific biomarkers of myocardial inflammation and remodeling processes as predictors of mortality in high-risk patients undergoing percutaneous mitral valve repair (MitraClip).

BACKGROUND: Specific matrix metalloproteinases (MMP-2, MMP-9) and inflammatory biomarkers (hsCRP, IL-6) were found to be consistently up-regulated in severe mitral valve regurgitation (MR) and are associated with mortality in heart failure patients. The aim of the present study was to examine the prognostic value of biomarkers of cardiac inflammation and remodeling processes in predicting mortality in patients with MR undergoing percutaneous mitral valve repair (PMVR). HYPOTHESIS: We hypothesize that increased cardiac inflammation and extracellular matrix turnover is predictive for mortality in patients with severe mitral regurgitation undergoing MitraClip. METHODS: A total of 210 consecutive patients undergoing PMVR were included. PMVR was performed according to standard clinical practice. Venous blood samples for biomarker analyses were collected prior to and 6 months after PMVR. Physiological parameters, medication use, safety events, and all-cause mortality were followed over 12 months. RESULTS: PMVR was performed successfully in all patients. Twelve months after PMVR there was an effective reduction in the severity of MR (P < 0.001), and an improvement in New York Heart Association class (P < 0.01) was documented. Elevated inflammatory biomarkers (AUChsCRP : 0.738 [IQR, 0.626-0.849], P = 0.001; AUCIL-6 : 0.811 [IQR, 0.724-0.899], P = 0.001) and biomarkers reflecting cardiac remodeling processes (AUCMMP-2 : 0.723 [IQR, 0.641-0.804], P = 0.001; AUCMMP-9 : 0.618 [IQR, 0.534-0.701], P = 0.01) were predictors of adverse cardiac events and mortality in patients with congestive heart failure undergoing PMVR. CONCLUSIONS: The present study is the first to identify biomarkers reflecting inflammation (hsCRP, IL-6) and cardiac remodeling processes (MMP-2, MMP-9) as predictors of mortality in high-risk patients undergoing PMVR.

Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes.

AIMS: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. METHODS AND RESULTS: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. CONCLUSION: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

Endocarditis after interventional repair of the mitral valve: Review of a dilemma.

BACKGROUND: The MitraClip procedure can be an alternative treatment option for patients with high surgical risk for whom surgical treatment is contraindicated. Patients with prosthetic material have an increased risk for infective endocarditis. HYPOTHESIS: Incidence, treatment and outcome of patients with endocarditis after interventional mitral valve repair are not known. METHODS: We searched for articles using PubMed using the terms "interventional mitral valve repair", "mitraclip" and "endocarditis". We have also searched for case reports in major congresses. Furthermore, we report two cases. RESULTS: Four cases of IE after MitraClip were found in addition to our cases. The leading cause is a bacterial infection, typically with staphylococcal bacteria. Approximately two thirds of these patients underwent surgery. Short-term outcome seems to be reasonable for these patients. During the early postoperative period and if Staphylococcus aureus can be cultivated mortality seems to be significantly elevated. CONCLUSION: IE after MitraClip procedure is a dilemma. While surgical bail-out seems to be the favorable treatment option, patients were rejected conventional surgery in first place due to their high operative risk. Best treatment recommendation must be made on an individual basis. Predisposing factors should be conscientiously addressed prior to the procedure.

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction.

CONTEXT: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes. OBJECTIVE: The study examined the early release kinetics of TnTuORF. MATERIALS AND METHODS: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n = 31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH). RESULTS: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18 ng/L versus 27 ng/L; cTnI median: 15 ng/L versus 25 ng/L). TnTuORF showed no variation. DISCUSSION: We observed a significantly greater increase in cTnI compared with cTnT. CONCLUSION: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.

N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro.

Myocardial infarction (MI) leads to loss and degradation of contractile cardiac tissue followed by sterile inflammation of the myocardium through activation and recruitment of innate and adaptive cells of the immune system. Recently, it was shown that cardiac myosin binding protein-C (cMyBP-C), a protein of the cardiac sarcomere, is degraded following MI, releasing a predominant N-terminal 40-kDa fragment (C0C1f) into myocardial tissue and the systemic circulation. We hypothesized that early release of C0C1f contributes to the initiation of inflammation and plays a key role in recruitment and activation of immune cells. Therefore, we investigated the role of C0C1f on macrophage/monocyte activation using both mouse bone marrow-derived macrophages and human monocytes. Here we demonstrate that C0C1f leads to macrophage/monocyte activation in vitro. Furthermore, C0C1f induces strong upregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and interleukin-1ß (IL-1ß)) in cultured murine macrophages and human monocytes, resulting in a pro-inflammatory phenotype. We identified the toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2), and Advanced Glycosylation End Product-Specific Receptor (RAGE) as potential receptors for C0C1f whose activation leads to mobilization of the NFκB signaling pathway, a central mediator of the pro-inflammatory signaling cascade. Thus, C0C1f appears to be a key player in the initiation of inflammatory processes and might also play an important role upon MI.