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.

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.

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.

Abnormal P-wave terminal force in lead V1 is a marker for atrial electrical dysfunction but not structural remodelling.

AIMS: There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V1 (PTFV1 ) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV1 as a marker for functional, electrical, and structural atrial remodelling. METHODS AND RESULTS: Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV1 and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV1 was assessed as the product of negative P-wave amplitude and duration in lead V1 and defined as abnormal if ≥4000 ms*µV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV1 . In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal PTFV1 (LA reservoir strain: 32.28 ± 12.86% vs. 22.75 ± 13.94%, P = 0.018; LA conduit strain: 18.87 ± 10.34% vs. 10.17 ± 8.26%, P = 0.004). Abnormal PTFV1 showed a negative correlation with LA conduit strain independent from clinical covariates (coefficient B: -7.336, 95% confidence interval -13.577 to -1.095, P = 0.022). CaMKII activity was significantly increased from (normalized to CaMKII expression) 0.87 ± 0.17 to 1.46 ± 0.15 in patients with an abnormal PTFV1 (P = 0.047). This increase in patients with an abnormal PTFV1 was independent from clinical covariates (coefficient B: 0.542, 95% confidence interval 0.057 to 1.027, P = 0.031). Atrial fibrosis was significantly lower with 12.32 ± 1.63% in patients with an abnormal PTFV1 (vs. 20.50 ± 2.09%, P = 0.006), suggesting PTFV1 to be a marker for electrical but not structural remodelling. CONCLUSIONS: Abnormal PTFV1 is an independent predictor for impaired atrial function and for electrical but not for structural remodelling. PTFV1 may be a promising tool to evaluate patients for atrial cardiomyopathy and for risk of atrial fibrillation.

Psychodynamic day treatment program for borderline personality disorder: factors that predict outcome and dropout: An observational study.

ABSTRACT: The objective of this study was to ascertain changes in symptoms of patients with borderline personality disorder undergoing psychodynamic day treatment with a duration of 9 months and the factors that predict clinical outcome or dropouts from the program.In an observational study, demographic characteristics (age, number of psychiatric hospitalizations, number of suicide attempts, current involvement in work or study activities), day doses of antipsychotic and antidepressant medication, psychiatric symptoms, and social functioning (Health of the Nation Outcome Scales), and symptoms of dissociation (Dissociative Experiences Scale) were assessed in patients at the beginning of treatment (N = 105). Further, psychiatric symptoms and social functioning were assessed at 3 stages: beginning of the program, end of the program, and 1-year follow-up. To study the differences between baseline values and values at the end of the treatment and follow-up values, the Wilcoxon signed-rank test was used. To discover baseline factors related to the effect of the treatment, Spearman correlation coefficients were calculated. To evaluate the differences between patients who completed the program (N = 67) and patients who dropped out (N = 38), differences in baseline factors between both groups were compared, using the Mann-Whitney test for independent samples.Improvement in symptoms (Health of the Nation Outcome Scales - version for external evaluators) at the end of the therapy (N = 67, P < .001) and at the 1-year follow-up (N = 46, P < .001) was found. Experience of an intimate relationship was positively related to clinical improvement at follow-up examinations (P < .001). Predictors of dropout included a higher number of psychiatric hospitalizations (P = .004), suicide attempts (P = .004), more severe pretreatment symptoms (P = .002), and symptoms of dissociation (P = .046).The results indicate that a psychodynamic day treatment is feasible for the treatment of less clinically disturbed patients with a history of intimate relationships. Patients with a higher number of previous psychiatric hospitalizations, more suicide attempts in the past, more severe pretreatment symptoms, and symptoms of dissociation are more likely not to complete the program.

Psychodynamic day treatment programme for patients with schizophrenia spectrum disorders: Dynamics and predictors of therapeutic change.

OBJECTIVES: The purpose of this study was to test whether a psychodynamically based group psychotherapeutic programme might improve symptoms, social functions, or quality of life in patients with schizophrenia spectrum disorders and to investigate factors that might predict clinical improvement or dropouts from the programme. DESIGN: A quantitative prospective cohort study. METHODS: We have investigated 81 patients with schizophrenia spectrum disorders who participated in a 9-month psychodynamically based psychotherapeutic day programme. The patients were assessed at the beginning and end of the programme, and then at 1-year follow-up. The assessment included psychotic manifestations (HoNOS), quality of life (WHOQOL-BREF), demographic data, and daily doses of medication. 21 patients dropped out from the programme, and 46 patients succeeded in undergoing follow-up assessment. RESULTS: The psychotic manifestations (self-rating version of HoNOS) and quality of life measured with WHOQOL-BREF (domains of social relationships and environment) were significantly improved at the end of the programme and at follow-up. However, the manifestations on the version for external evaluators of HoNOS were improved only at follow-up. Years of psychiatric treatment, number of hospitalizations or suicide attempts, and experience of relationships with a partner were negatively related to clinical improvement, whereas symptom severity, current working, or study activities were related positively. CONCLUSIONS: The results show that a group psychodynamic programme may improve the clinical status and quality of life of patients with schizophrenia spectrum disorders. This type of programme is more beneficial for patients with higher pre-treatment symptom severity and the presence of working or study activities. PRACTITIONER POINTS: A psychodynamically based group programme improves the clinical status and quality of life in patients with schizophrenia spectrum disorders. Data indicate that changes on the subjective level are detectable by the end of the programme, while changes on the objective level are detectable at follow-up assessment. Symptom severity and working or study activities are positively related to the clinical improvement in this type of programme, while a high number of years in psychiatric treatment or psychiatric hospitalizations are negatively related. The doses of medication (antipsychotics or antidepressants) show no significant relationship to clinical improvement.