Treatment of sleep apnoea early after myocardial infarction with adaptive servo-ventilation - a proof-of-concept randomised controlled trial.

INTRODUCTION: Sleep-disordered breathing has been associated with less myocardial salvage and smaller infarct size reduction after acute myocardial infarction (AMI). The Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation (TEAM-ASV I) trial investigated the effects of adding adaptive servo-ventilation (ASV) for sleep-disordered breathing (SDB) to standard therapy on myocardial salvage index (MSI) and change in infarct size within 12 weeks after AMI. METHODS: In this multicentre, randomised, open-label trial, patients with AMI and successful percutaneous coronary intervention within 24 h after symptom onset plus SDB (apnoea-hypopnoea index ≥15/h) were randomised to standard medical therapy alone (control) or plus ASV (starting 3.6±1.4 days post-AMI). The primary outcome was MSI at 12 weeks post-AMI. Cardiac magnetic resonance (CMR) imaging was performed at ≤5 days and 12 weeks after AMI. RESULTS: Seventy-six individuals were enrolled from February 2014 to August 2020; 39 had complete CMR data for analysis of the primary endpoint. MSI was significantly higher in the ASV versus control group (difference 14.6% of left ventricular mass [LVM]; 95% confidence interval 0.14-29.1; p=0.048). At 12 weeks, absolute [interquartile range] (6.6 [4.8-8.5] versus 2.8 [0.9-4.8] %LVM; p=0.003) and relative (44 [30-57] versus 21 [6-35] % of baseline; p=0.013) reductions in infarct size were greater in the ASV versus control group. No serious treatment-related adverse events occurred. CONCLUSIONS: Early treatment of SDB with ASV improved the MSI and decreased the infarct size at 12 weeks after AMI. Larger randomised trials are required to confirm these findings.

3D vena contracta area after MitraClip© procedure: precise quantification of residual mitral regurgitation and identification of prognostic information.

BACKGROUND: Percutaneous mitral valve repair (PMVR) is increasingly performed in patients with severe mitral regurgitation (MR). Post-procedural MR grading is challenging and an unsettled issue. We hypothesised that the direct planimetry of vena contracta area (VCA) by 3D-transoesophageal echocardiography allows quantifying post-procedural MR and implies further prognostic relevance missed by the usual ordinal scale (grade I-IV). METHODS: Based on a single-centre PMVR registry containing 102 patients, the association of VCA reduction and patients' functional capacity measured as six-minute walk distance (6 MW) was evaluated. 3D-colour-Doppler datasets were available before, during and 4 weeks after PMVR. RESULTS: Twenty nine patients (age 77.0 ± 5.8 years) with advanced heart failure (75.9% NYHA III/IV) and severe degenerative (34%) or functional (66%) MR were eligible. VCA was reduced in all patients by PMVR (0.99 ± 0.46 cm2 vs. 0.22 ± 0.15 cm2, p < 0.0001). It remained stable after median time of 33 days (p = 0.999). 6 MW improved after the procedure (257.5 ± 82.5 m vs. 295.7 ± 96.3 m, p < 0.01). Patients with a decrease in VCA less than the median VCA reduction showed a more distinct improvement in 6 MW than patients with better technical result (p < 0.05). This paradoxical finding was driven by inferior results in very large functional MR. CONCLUSIONS: VCA improves the evaluation of small residual MR. Its post-procedural values remain stable during a short-term follow-up and imply prognostic information for the patients' physical improvement. VCA might contribute to a more substantiated estimation of treatment success in the heterogeneous functional MR group.

Nocturnal hypoxemic burden is associated with epicardial fat volume in patients with acute myocardial infarction.

BACKGROUND: Increased epicardial fat volume (EFV) is a common feature of patients with sleep-disordered breathing (SDB), is considered as an established marker of cardiovascular risk, and is associated with adverse cardiovascular events after myocardial infarction (MI). METHODS: To investigate the association between different measures of SDB severity and EFV after acute MI, we enrolled 105 patients with acute MI in this study. Unattended in-hospital polysomnography was performed to determine the number of apneas and hypopneas per hour during sleep (apnea-hypopnea index, AHI). To determine nocturnal hypoxemic burden, we used pulse oximetry and applied a novel parameter, the hypoxia load representing the integrated area of desaturation divided by total sleep time (HLTST). Of 105 patients, 56 underwent cardiovascular magnetic resonance to define EFV. RESULTS: HLTST was significantly associated with EFV (r2 = 0.316, p = 0.025). Multivariate linear regression analysis accounting for age, sex, body mass index, smoking, and left ventricular mass demonstrated that the HLTST was an independent modulator of EFV (B-coefficient 0.435 (95% CI 0.021-0.591); p = 0.015). In contrast, AHI or established measures of hypoxemia did not correlate with EFV. CONCLUSIONS: HLTST, a novel parameter to determine nocturnal hypoxemic burden, and not AHI as an event-based measure of SDB, was associated with EFV in patients with acute MI. Further studies are warranted to confirm the link between nocturnal hypoxemia and EFV and to determine the prognostic value of a more detailed characterization of nocturnal hypoxemic burden in patients with high cardiovascular risk.

Drug Coated Balloon Is Less Effective for Treatment of DES In-Stent Restenosis Both in Native Coronary Arteries and Saphenous Vein Grafts: Results From a Bicenter Registry.

BACKGROUND: The paclitaxel drug coated balloon (DCB) is an established treatment for bare metal stent (BMS) in-stent restenosis (ISR) in native coronary arteries. The evidence of DCB-application for drug eluting stent (DES) ISR both in native coronaries and saphenous vein grafts (SVG) is limited. Aim of our study was to compare the differential efficacy of DCB for treatment of BMS- and DES-ISR in native coronary vessels and SVGs. METHODS AND RESULTS: N = 135 DCB-treated patients with available follow up (FU) angiography were included in this retrospective study. Patients received treatment between April 2009 and March 2013 at 2 tertiary care hospitals in Germany. DCB was applied in BMS-ISR (n = 65; 48%) and DES-ISR (n = 70; 52%). DCB-treated lesions were located in native coronary arteries (n = 110; 81%; BMS-ISR: n = 58; 53%; DES-ISR: n = 52; 47%) and SVGs (n = 25; 19%; BMS-ISR: n = 7, 28%; DES-ISR: n = 18, 72%). Median FU was 12 months. Endpoints were binary restenosis and target lesion revascularization (TLR). Binary restenosis (29% vs. 57%; P < 0.01) and TLR (18% vs. 46%; P < 0.01) were significantly more frequent in DES-ISR versus BMS-ISR. In SVGs, TLR was required in 72% (DES-ISR) versus 14% (BMS-ISR); P = 0.02. In the Kaplan-Meier-analysis freedom from both endpoints was significantly decreased in the DES-lesions both in the total population (binary restenosis P < 0.01; TLR P < 0.01) and native coronaries (binary restenosis P = 0.02; TLR P = 0.04). CONCLUSIONS: DCB treatment is less effective in DES-ISR than in BMS-ISR. The diminished efficacy of DCB treatment is even more pronounced in DES-ISR located within degenerated SVGs.

N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

AIM: Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. METHODS: New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. RESULTS: Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. CONCLUSIONS: During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The current study emphasizes a strong association of the tubular biomarkers NAG and KIM-1 with CKD progression in chronic heart failure and suggests their usefulness as cardiorenal markers.

Sleep disordered breathing and enlargement of the right heart after myocardial infarction.

Structural and functional integrity of the right heart is important in the prognosis after acute myocardial infarction (AMI). The objective of this study was to assess the impact of sleep disordered breathing (SDB) on structure and function of the right heart early after AMI. 54 patients underwent cardiovascular magnetic resonance 3-5 days and 12 weeks after AMI, and were stratified according to the presence of SDB, defined as an apnoea-hypopnoea index of ≥ 15 events · h(-1). 12 weeks after AMI, end-diastolic volume of the right ventricle had increased significantly in patients with SDB (n=27) versus those without (n=25) (mean ± sd 14 ± 23% versus 0 ± 17%, p=0.020). Multivariable linear regression analysis accounting for age, sex, body mass index, smoking, left ventricular mass and left ventricular end-systolic volume showed that the apnoea-hypopnoea index was significantly associated with right ventricular end-diastolic volume (B-coefficient 0.315 (95% CI 0.013-0.617); p=0.041). From baseline to 12 weeks, right atrial diastolic area increased more in patients with SDB (2.9 ± 3.7 cm(2) versus 1.0 ± 2.4 cm(2), p=0.038; when adjusted for left ventricular end systolic volume, p=0.166). SDB diagnosed shortly after AMI predicts an increase of right ventricular end-diastolic volume and possibly right atrial area within the following 12 weeks. Thus, SDB may contribute to enlargement of the right heart after AMI.

Simplified Method for Insertion of Steerable Guide into the Left Atrium Using a Pigtail Guide Wire During the MitraClip(®) Procedure: A Technical Tip.

BACKGROUND: To assess whether a new floppy pigtail guidewire provides sufficient support for introduction of the 22F-steerable guide catheter (SG) into the left atrium and is less time-consuming during the MitraClip(®) -procedure without necessity of probing and inserting a stiff wire into the pulmonary vein. METHODS: In group 1, traditional probing of the left upper pulmonary vein and insertion of a standard stiff wire was used. In group 2, direct insertion of the floppy pigtail guidewire directly after transseptal puncture was used. RESULTS: Patients in group 1 (n = 18) and group 2 (n = 21) did not differ significantly with respect to mitral regurgitation severity (3.2 ± 0.4 vs 3.2 ± 0.4; P = 0.814) and etiology (functional 78% vs 71%, P = 0.651). Comparing both methods, a significant reduction in time-to-SG was observed in group 2 versus group 1 (17 ± 7 minutes vs 30 ± 11 minutes; P = 0.001). The rate of crossing failures was 0% with use of the floppy pigtail guidewire as well as with the traditional technique. No complications were observed with use of the floppy pigtail guidewire. CONCLUSIONS: Utilization of a thin, floppy pigtail guidewire for left atrium access is safe and markedly accelerates insertion of the SG for the MitraClip(®) -procedure without crossing failures of the atrial septum.

Cardiovascular magnetic resonance assessment of the aortic valve stenosis: an in vivo and ex vivo study.

BACKGROUND: Aortic valve area (AVA) estimation in patients with aortic stenosis may be obtained using several methods. This study was undertaken to verify the cardiovascular magnetic resonance (CMR) planimetry of aortic stenosis by comparing the findings with invasive catheterization, transthoracic (TTE) as well as tranesophageal echocardiography (TEE) and anatomic CMR examination of autopsy specimens. METHODS: Our study was performed in eight patients with aortic valve stenosis. Aortic stenosis was determined by TTE and TEE as well as catheterization and CMR. Especially, after aortic valve replacement, the explanted aortic valves were examined again with CMR ex vivo model. RESULTS: The mean AVA determined in vivo by CMR was 0.75 ± 0.09 cm(2) and ex vivo by CMR was 0.65 ± 0.09 cm(2) and was closely correlated (r = 0.91, p < 0.001). The mean absolute difference between AVA derived by CMR ex vivo and in vivo was -0.10 ± 0.04 cm(2). The mean AVA using TTE was 0.69 ± 0.07 with a significant correlation between CMR ex vivo (r = 0.85, p < 0.007) and CMR in vivo (r = 0.86, p < 0.008). CMR ex vivo and in vivo had no significant correlation with AVA using Gorlin formula by invasive catheterization or using planimetry by TEE. CONCLUSION: In this small study using an ex vivo aortic valve stenosis model, the aortic valve area can be reliably planimetered by CMR in vivo and ex vivo with a well correlation between geometric AVA by CMR and the effective AVA calculated by TTE.

Impact of sleep-disordered breathing on myocardial salvage and infarct size in patients with acute myocardial infarction.

AIMS: Sleep-disordered breathing (SDB) may be a risk factor for expansion of infarct size early after acute myocardial infarction (MI) by exposing the heart to repetitive oxygen desaturations and increased cardiac afterload. The objective of this study was to assess the impact of SDB on myocardial salvage and infarct size within 3 months after acute MI. METHODS AND RESULTS: Patients with acute MI and percutaneous coronary intervention were enrolled in this prospective observational study. All patients underwent cardiovascular magnetic resonance (CMR) to define salvaged myocardium and infarct size within three to five days and at 3 months after acute MI. Patients were stratified according to apnoea-hypopnoea index (AHI) assessed by polysomnography at baseline into those with (AHI ≥ 15/h) and without (AHI < 15/h) SDB. Of the 56 patients included, 29 (52%) had SDB. The area at risk between both groups was similar (40 ± 12% vs. 40 ± 14%, P = 0.925). Patients with SDB had significantly less salvaged myocardium (myocardial salvage index 52% vs. 77%, P < 0.001), smaller reduction in infarct size (0.3% vs. 6.5%, P < 0.001) within 3 months after acute MI, a larger final infarct size (23% vs. 12%, P < 0.001), and a lower final left ventricular ejection fraction (48% vs. 54%, P = 0.023). In a multivariate analysis, including established risk factors for large MI, AHI was independently associated with less myocardial salvage and a larger infarct size 3 months after acute MI. CONCLUSIONS: Sleep-disordered breathing was associated with less myocardial salvage and a smaller reduction in infarct size. These findings suggest a contribution of SDB to impaired healing of MI.

Inflammation and Fibrosis in Sleep-Disordered Breathing after Acute Myocardial Infarction.

BACKGROUND: After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB. METHODS AND RESULTS: This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h-1). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP (p = 0.028). Similarly, only SDB was independently associated with PIIINP (p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP (p = 0.012) and PIIINP (p = 0.006) levels. CONCLUSIONS: The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

Association of Coronary Collaterals and Myocardial Salvage Measured by Serial Cardiac Magnetic Resonance Imaging after Acute Myocardial Infarction.

BACKGROUND: Coronary collateral flow in angiography has been linked with lower mortality rates in patients with coronary artery disease. However, the relevance of the underlying mechanism is sparse. Therefore, we tested the hypothesis that in patients with acute myocardial infarction (AMI), relevant coronary collateral flow is associated with more salvaged myocardium and lower risk of developing heart failure. METHODS AND RESULTS: Patients with first AMI who received a percutaneous coronary intervention within 24 h after symptom onset were classified visually by assigning a Cohen-Rentrop Score (CRS) ranging between 0 (no collaterals) and 3 (complete retrograde filling of the occluded vessel). All 36 patients included in the analysis underwent cardiac magnetic resonance examination within 3 to 5 days after myocardial infarction and after 12 weeks. Patients with relevant collateral flow (CRS 2-3) to the infarct-related artery had significantly smaller final infarct size compared to those without (7 ± 4% vs. 20 ± 12%, p < 0.001). In addition, both groups showed improvement in left ventricular ejection fraction early after AMI, whereas the recovery was greater in CRS 2-3 (+8 ± 5% vs. +3 ± 5%, p = 0.015). CONCLUSION: In patients with first AMI, relevant collateral flow to the infarct-related artery was associated with more salvaged myocardium at 12 weeks, translating into greater improvement of systolic left ventricular function. The protective effect of coronary collaterals and the variance of infarct location should be further investigated in larger studies.

Natural course of sleep-disordered breathing after acute myocardial infarction.

The aim of this study was to test whether an improvement of left ventricular ejection fraction (EF) in the early phase after acute myocardial infarction is associated with a reduction of the severity of central and obstructive sleep apnoea. 40 consecutive patients with acute myocardial infarction underwent polysomnography and cardiovascular magnetic resonance imaging within 5 days and 12 weeks after the event to assess sleep apnoea and cardiac function. We stratified the sample in patients who improved their left ventricular EF within 12 weeks by ≥ 5% (improved EF group, ΔEF 9 ± 1%, n=16) and in those who did not (unchanged EF group, ΔEF -1 ± 1%, n=24). Prevalence of sleep apnoea (≥ 15 apnoea and hypopnoea events·h(-1)) within ≤ 5 days after myocardial infarction was 55%. Apnoea and hypopnoea events·h(-1) were significantly more reduced in the improved EF group compared with the unchanged EF group (-10 ± 3 versus 1 ± 3 events·h(-1); p=0.036). This reduction was based on a significant alleviation of obstructive events (-7 ± 2 versus 4 ± 3 events·h(-1); p=0.009), while the reduction of central events was similar between groups (p=0.906). An improvement of cardiac function early after myocardial infarction is associated with an alleviation of sleep apnoea. This finding suggests that re-evaluation of treatment indication for sleep apnoea is needed when a change in cardiac function occurs.

Obstructive sleep apnoea is associated with the development of diastolic dysfunction after myocardial infarction with preserved ejection fraction.

BACKGROUND: Left ventricular diastolic dysfunction is a predictor of adverse outcome after acute myocardial infarction (AMI). We aimed to test if sleep-disordered breathing (SDB) contributes to the development of diastolic dysfunction in patients with preserved left ventricular ejection fraction after AMI. METHOD: Patients with AMI, percutaneous coronary intervention and an ejection fraction ≥50% were included in this sub-analysis of a prospective observational study. Patients with AMI (n = 41) underwent cardiovascular magnetic resonance imaging (volume-time curve analysis) to define diastolic function by means of the normalised peak filling rate [nPFR; (end diastolic volume/second)]. In patients with AMI, the nPFR was assessed within <5 days and three months after AMI. Patients with AMI were stratified in patients with (apnoea-hypopnoea index, AHI ≥15/h) and without (AHI <15/h) SDB as assessed by polysomnography. RESULTS: At the time of AMI, the nPFR was similar between patients with and without SDB (2.90 ± 0.54 vs. 3.03 ± 1.20, p = 0.662). Within three months after AMI, diastolic function was significantly lower in patients with SDB than in patients without SDB (ΔnPFR: -0.83 ± 0.14 vs. 0.03 ± 0.14; p < 0.001; ANCOVA, adjusted for baseline nPFR). In contrast to central AHI, obstructive AHI was associated with a lower nPFR three months after AMI, after accounting for established risk factors for diastolic dysfunction [multiple linear regression analysis, B (95%CI): -0.036 (-0.063 to -0.009), p = 0.011]. CONCLUSION: Our data indicate that obstructive sleep apnoea impairs diastolic function early after myocardial infarction.

Sleep-Disordered Breathing Is Associated With Reduced Left Atrial Strain Measured by Cardiac Magnetic Resonance Imaging in Patients After Acute Myocardial Infarction.

AIMS: Sleep disordered breathing (SDB) is known to cause left atrial (LA) remodeling. However, the relationship between SDB severity and LA dysfunction is insufficiently understood and may be elucidated by detailed feature tracking (FT) strain analysis of cardiac magnetic resonance images (CMR). After myocardial infarction (MI), both the left ventricle and atrium are subjected to increased stress which may be substantially worsened by concomitant SDB that could impair consequential healing. We therefore analyzed atrial strain in patients at the time of acute MI and 3 months after. METHODS AND RESULTS: 40 patients with acute MI underwent CMR and polysomnography (PSG) within 3-5 days after MI. Follow-up was performed 3 months after acute MI. CMR cine data were analyzed using a dedicated FT software. Atrial strain (ε) and strain rate (SR) for atrial reservoir ([εs]; [SRs]), conduit ([εe]; [SRe]) and booster function ([εa]; [SRa]) were measured in two long-axis views. SDB was defined by an apnea-hypopnea-index (AHI) ≥15/h. Interestingly, LA εs and εe were significantly reduced in patients with SDB and correlated negative with AHI as a measure of SDB severity at both baseline and follow-up. Intriguingly, patients that exhibited a reduced AHI at follow-up were more likely to have developed improved atrial reservoir and conduit strain (linear regression, p=0.08 for εs and εe). Patients with improved SDB (ΔAHI < -5/h) exhibited a mean improvement of LA reservoir strain of +7.2 ± 8.4% whereas patients with SDB deterioration (ΔAHI> + 5/h) showed a mean decrease of -5.3 ± 11.0% (p = 0.0131). Similarly, the difference for LA conduit function was +4.8 ± 5.9% (ΔAHI < -5/h) vs -3.6 ± 8.8% (ΔAHI> +5/h). Importantly, conventional volumetric parameters for atrial function (LA area, LA volume index) did not correlate with AHI at baseline or follow-up. CONCLUSION: Our results show that LA function measured by CMR strain but not by volumetry is impaired in patients with SDB during acute cardiac injury. Consistent with a mechanistic association, improvement of SBD at follow-up resulted in improved LA strain. LA strain measurement might thus provide insight into atrial function in patients with SDB.

High-sensitive troponin T in chronic heart failure correlates with severity of symptoms, left ventricular dysfunction and prognosis independently from N-terminal pro-b-type natriuretic peptide.

BACKGROUND: Troponin T is an established marker of myocardial ischemia. We speculated that the role of the new high-sensitive troponin T (hs-cTnT) might expand towards non-ischemic myocardial disease, indicate disease severity and allow for prognostication in chronic heart failure. METHODS: Hs-cTnT (Roche Diagnostics, Mannheim, Germany) was assessed in 233 individuals with chronic heart failure (n=149) or healthy controls (n=84). RESULTS: Hs-cTnT was significantly elevated in patients with chronic heart failure [0.018 ng/mL, interquartile range (IQR) 0.009-0.036 ng/mL, vs. controls 0.003 ng/mL, 0.003-0.003 ng/mL, p<0.001] and positively correlated with N-terminal pro-b-type natriuretic peptide (NT-proBNP) (r=0.79, p<0.001). Hs-cTnT increased stepwise and signitificantly according to clinical (NYHA stage) as well as functional (LV ejection fraction, fluid retention) severity (each p<0.001). At a binary cutpoint of 0.014 ng/mL, hs-TropT was a significant predictor of all-cause mortality and all-cause mortality or rehospitalization for congestive heart failure (each p≤0.01). Of note, the prognostic value of hs-TropT was independent and additive to that of NT-proBNP. CONCLUSIONS: Hs-cTnT increases stepwise with the severity of symptoms and LV dysfunction and offers important prognostic information in chronic heart failure, independently from and additive to NT-proBNP. The utility of hs-cTnT expands beyond acute myocardial ischemia and towards chronic heart failure.

Central Sleep Apnea Is Associated with an Abnormal P-Wave Terminal Force in Lead V1 in Patients with Acute Myocardial Infarction Independent from Ventricular Function.

Sleep-disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease. We have recently shown that an elevation of the electrocardiographic (ECG) parameter P wave terminal force in lead V1 (PTFV1) is linked to atrial proarrhythmic activity by stimulation of reactive oxygen species (ROS)-dependent pathways. Since SDB leads to increased ROS generation, we aimed to investigate the relationship between SDB-related hypoxia and PTFV1 in patients with first-time acute myocardial infarction (AMI). We examined 56 patients with first-time AMI. PTFV1 was analyzed in 12-lead ECGs and defined as abnormal when ≥4000 µV*ms. Polysomnography (PSG) to assess SDB was performed within 3-5 days after AMI. SDB was defined by an apnea-hypopnea-index (AHI) >15/h. The multivariable regression analysis showed a significant association between SDB-related hypoxia and the magnitude of PTFV1 independent from other relevant clinical co-factors. Interestingly, this association was mainly driven by central but not obstructive apnea events. Additionally, abnormal PTFV1 was associated with SDB severity (as measured by AHI, B 21.495; CI [10.872 to 32.118]; p < 0.001), suggesting that ECG may help identify patients suitable for SDB screening. Hypoxia as a consequence of central sleep apnea may result in atrial electrical remodeling measured by abnormal PTFV1 in patients with first-time AMI independent of ventricular function. The PTFV1 may be used as a clinical marker for increased SDB risk in cardiovascular patients.

Occurrence of Coronary Collaterals in Acute Myocardial Infarction and Sleep Apnea.

Background In patients with acute myocardial infarction (MI), cardioprotective effects of obstructive sleep apnea are postulated on account of hypoxemic preconditioning. The aim of this single-center substudy was to investigate a potential association between obstructive sleep apnea and the presence of coronary collaterals in patients with first-time acute MI who have been enrolled in an ongoing, multicenter clinical trial. Methods and Results In TEAM-ASV I (Treatment of Sleep Apnea Early After Myocardial Infarction With Adaptive Servo-Ventilation Trial; NCT02093377) patients with first acute MI who received a coronary angiogram within 24 hours after onset of symptoms underwent polygraphy within the first 3 days. Coronary collaterals were classified visually by assigning a Cohen-Rentrop Score (CRS) ranging between 0 (no collaterals) and 3. Of 94 analyzed patients, 14% had significant coronary collaterals with a CRS ≥2. Apnea-Hypopnea Index (AHI) score was significantly higher in patients with CRS ≥2 compared with those with CRS <2 (31/hour [11-54] versus 13/hour [4-27]; P=0.032). A multivariable regression model revealed a significant association between obstructive AHI and CRS ≥2 that was independent of age, sex, body mass index, and culprit lesion left anterior descending artery (odds ratio [OR], 1.06; 95% CI, 1.01-1.12; P=0.023), but no significant association between coronary collaterals and central AHI (OR, 1.02; 95% CI, 0.97-1.08; P=0.443). Conclusions Patients with first-time acute MI had more extensive coronary collateralization with an increased AHI or rather an increased obstructive AHI. This finding supports the hypothesis that obstructive sleep apnea exerts potential cardioprotective effects, in addition to its known deleterious effects, in patients with acute MI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02093377.

The impact of epicardial adipose tissue in patients with acute myocardial infarction.

AIMS: Epicardial adipose tissue (EAT) has been linked to impaired reperfusion success after percutaneous coronary intervention (PCI). Whether EAT predicts myocardial damage in the early phase after acute myocardial infarction (MI) is unclear. Therefore, we investigated whether EAT in patients with acute MI is associated with more microvascular obstruction (MVO), greater ST-deviation, larger infarct size and reduced myocardial salvage index (MSI). METHODS AND RESULTS: This retrospective analysis of a prospective observational study including patients with acute MI (n = 54) undergoing PCI and 12 healthy matched controls. EAT, infarct size and MSI were analyzed with cardiac magnetic resonance imaging, conducted 3-5 days and 12 weeks after MI. Patients with acute MI showed higher EAT volume than healthy controls (46 [25.;75. percentile: 37;59] vs. 24 [15;29] ml, p < 0.001). The high EAT group (above median) showed significantly more MVO (2.22 [0.00;5.38] vs. 0.0 [0.00;2.18] %, p = 0.004), greater ST-deviation (0.38 [0.22;0.55] vs. 0.15 [0.03;0.20] mV×10-1, p = 0.008), larger infarct size at 12 weeks (23 [17;29] vs. 10 [4;16] %, p < 0.001) and lower MSI (40 [37;54] vs. 66 [49;88] %, p < 0.001) after PCI than the low EAT group. After accounting for demographic characteristics, body-mass index, heart volume, infarct location, TIMI-flow grade as well as apnea-hypopnea index, EAT was associated with infarct size at 12 weeks (B = 0.38 [0.11;0.64], p = 0.006), but not with MSI. CONCLUSIONS: Patients with acute MI showed higher volume of EAT than healthy individuals. High EAT was linked to more MVO and greater ST-deviation. EAT was associated with infarct size, but not with MSI.

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair.

BACKGROUND AND HYPOTHESIS: The acquired von Willebrand syndrome (AvWS), which predisposes to bleeding events, is often related to valvular heart diseases. We investigated possible implications of AvWS and factor VIII levels in patients with moderate to severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). METHODS AND RESULTS: 123 patients with moderate to severe MR were prospectively enrolled. Complete measurements of von Willebrand Factor activity (vWFAct), von Willebrand Factor antigen (vWFAg), and factor VIII expression before and 4 weeks after TMVR were available in 85 patients. At baseline, seven patients had a history of gastrointestinal bleeding, two patients suffered bleeding events during their hospital stay, and one patient had a bleeding 4 weeks after TMVR. Even though vWFAct, vWFAct/vWFAg ratio and vWFAg values did not change after TMVR, we observed a significantly lower vWFAct/vWFAg ratio in patients with primary MR as compared to patients with secondary MR both at baseline (p = 0.022) and 4 weeks following the TMVR procedure (p = 0.003). Additionally, patients with a mean mitral valve gradient ≥4 mmHg after TMVR had significantly lower vWFAct/vWFAg ratios as compared to patients with a mean mitral valve gradient <4 mmHg (p = 0.001). CONCLUSIONS: MR of primary etiology was associated with lower vWFAct/vWFAg ratio, hinting toward HMWM loss due to shear stress caused by eccentric regurgitation jets. In addition, morphological changes leading to postprocedural transmitral gradients ≥4 mmHg were related to lower vWFAct/vWFAg ratio 4 weeks after the procedure. Alterations of the vWFAct/vWFAg ratio in turn did not translate into a greater risk for bleeding events.

Obstructive sleep apnoea but not central sleep apnoea is associated with left ventricular remodelling after acute myocardial infarction.

OBEJCTIVE: Obstructive sleep apnoea (OSA) increases left ventricular transmural pressure more than central sleep apnoea (CSA) owing to negative intrathoracic pressure swings. We tested the hypothesis that the severity of OSA, and not CSA, is therefore associated with spheric cardiac remodelling after acute myocardial infarction. METHODS: This sub-analysis of a prospective observational study included 24 patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. Spheric remodelling, calculated according to the sphericity index, was assessed by cardiac magnetic resonance imaging at baseline and 12 weeks after acute myocardial infarction. OSA and CSA [apnoea-hypopnoea index (AHI) ≥ 5/hour] were diagnosed by polysomnography. RESULTS: Within 12 weeks after acute myocardial infarction, patients with OSA exhibited a significant increase in systolic sphericity index compared to patients without sleep-disordered breathing (no SDB) and patients with CSA (OSA vs. CSA vs. no SDB: 0.05 ± 0.04 vs. 0.01 ± 0.04 vs. - 0.03 ± 0.03, p = 0.002). In contrast to CSA, the severity of OSA was associated with an increase in systolic sphericity index after accounting for TIMI-flow before percutaneous coronary intervention, infarct size, pain-to-balloon-time and systolic blood pressure [OSA: B (95% CI) 0.443 (0.021; 0.816), p = 0.040; CSA: 0.193 (- 0.134; 0.300), p = 0.385]. CONCLUSION: In contrast to CSA and no SDB, OSA is associated with spheric cardiac remodelling within the first 12 weeks after acute myocardial infarction. Data suggest that OSA-related negative intrathoracic pressure swings may contribute to this remodelling after acute myocardial infaction.