Standardized angiographic projections allow evaluation of coronary artery side branches with quantitative flow ratio (QFR).

Quantitative flow ratio (QFR) is a novel, software-based noninvasive method for the quantitative evaluation of coronary physiology. QFR results correlate with invasive FFR measurements in the three main epicardial coronary arteries. However, QFR data for the evaluation of coronary side branches (SB) are scarce. The evaluation of QFR-performance of SB was retrospective and prospective. Eighty-seven patients with suspected chronic coronary syndrome, who received angiography using routine core lab projections, were retrospectively analyzed. On the second part 37 patients, who received angiography using recommended standardized coronary angiography projections, were prospectively analyzed. Quantitative analysis was performed for SB with a maximum lumen diameter proximal of ≥2 mm based on quantitative coronary angiography (QCA) by two certified experts with the software QAngio XA 3D 3.2. Using routine projections, QFR computation in 55 % of the SB were obtained (123 out of 224). Using standardized projections, 85 % of SB were computed by QFR (64 out of 75; p < 0.001 vs routine projections). The fluoroscopy time for recommended projections was not significantly different as opposed to routine projections (3.75 ± 2.2 vs. 4.58 ± 3.00 min, p = 2.6986). Using the standardized projections was associated with a higher amount of contrast medium (53.44 ± 24.23 vs. 87.95 ± 43.73 ml, p < 0.01), longer overall procedure time (23.23 ± 16.35 vs. 36.14 ± 17.21 min, p < 0.01) and a higher dose area product (1152.28 ± 576.70 vs. 2540.68 ± 1774.07 cGycm2, p < 0.01). Our study shows that the blood flow of the vast majority of coronary SB can be determined non-invasively by QFR in addition to the main epicardial coronary arteries when standardized projections are used.

Effect of maximum exercise on left ventricular deformation and its correlation with cardiopulmonary exercise capacity in competitive athletes.

BACKGROUND: Global longitudinal strain (GLS) and global myocardial work index (GWI) allow early detection of subclinical changes in left ventricular (LV) systolic function. The aim of the study was to investigate the immediate effects of maximum physical exercise by different exercise testing methods on early post exercise LV deformation parameters in competitive athletes and to analyze their correlation with cardiopulmonary exercise capacity. METHODS: To reach maximum physical exercise, cardiopulmonary exercise testing (CPET) was performed by semi-recumbent ergometer in competitive handball players (n = 13) and by treadmill testing in competitive football players (n = 19). Maximum oxygen uptake (VO2max) indexed to body weight (relative VO2max) was measured in all athletes. Transthoracic echocardiography and blood pressure measurements were performed at rest and 5 min after CPET in all athletes. GLS, GWI and their changes before and after CPET (ΔGLS, ΔGWI) were correlated with (relative) VO2max. RESULTS: In handball and football players, GLS and GWI did not differ significantly before and after CPET. There were no significant correlations between GLS and relative VO2max, but moderate correlations were found between ΔGWI and relative VO2max in handball (r = 0.631; P = 0.021) and football players (r = 0.592; P = 0.008). Furthermore, handball (46.7 ml/min*kg ± 4.7 ml/min*kg vs. 37.4 ml/min*kg ± 4.2; P = 0.004) and football players (58.3 ml/min*kg ± 3.7 ml/min*kg vs. 49.7 ml/min*kg ± 6.8; P = 0.002) with an increased ΔGWI after CPET showed a significant higher relative VO2max. CONCLUSION: Maximum physical exercise has an immediate effect on LV deformation, irrespective of the used testing method. The correlation of relative VO2max with ΔGWI in the early post exercise period, identifies ΔGWI as an echocardiographic parameter for characterizing the current individual training status of athletes.

High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. METHODS: Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. RESULTS: Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). CONCLUSION: In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.

The impact of upright posture on left ventricular deformation in athletes.

Besides LV ejection fraction (LVEF), global longitudinal strain (GLS) and global myocardial work index (GWI) are increasingly important for the echocardiographic assessment of left ventricular (LV) function in athletes. Since exercise testing is frequently performed on a treadmill, we investigated the impact of upright posture on GLS and GWI. In 50 male athletes (mean age 25.7 ± 7.3 years) transthoracic echocardiography (TTE) and simultaneous blood pressure measurements were performed in upright and left lateral position. LVEF (59.7 ± 5.3% vs. 61.1 ± 5.5%; P = 0.197) was not affected by athletes' position, whereas GLS (- 11.9 ± 2.3% vs. - 18.1 ± 2.1%; P < 0.001) and GWI (1284 ± 283 mmHg% vs. 1882 ± 247 mmHg%; P < 0.001) were lower in upright posture. Longitudinal strain was most frequently reduced in upright posture in the mid-basal inferior, and/or posterolateral segments. Upright posture has a significant impact on LV deformation with lower GLS, GWI and regional LV strain in upright position. These findings need to be considered when performing echocardiography in athletes.

SARS-CoV2 infection: functional and morphological cardiopulmonary changes in elite handball players.

There is increasing evidence of cardiac involvement post-SARS-CoV-2 infections in symptomatic as well as in oligo- and asymptomatic athletes. This study aimed to characterize the possible early effects of SARS-CoV-2 infections on myocardial morphology and cardiopulmonary function in athletes. Eight male elite handball players (27 ± 3.5 y) with past SARS-CoV-2 infection were compared with four uninfected teammates (22 ± 2.6 y). Infected athletes were examined 19 ± 7 days after the first positive PCR test. Echocardiographic assessment of the global longitudinal strain under resting conditions was not significantly changed (- 17.7% vs. - 18.1%). However, magnetic resonance imaging showed minor signs of acute inflammation/oedema in all infected athletes (T2-mapping: + 4.1 ms, p = 0.034) without reaching the Lake-Louis criteria. Spiroergometric analysis showed a significant reduction in VO2max (- 292 ml/min, - 7.0%), oxygen pulse (- 2.4 ml/beat, - 10.4%), and respiratory minute volume (VE) (- 18.9 l/min, - 13.8%) in athletes with a history of SARS-CoV2 infection (p < 0.05, respectively). The parameters were unchanged in the uninfected teammates. SARS-CoV2 infection caused impairment of cardiopulmonary performance during physical effort in elite athletes. It seems reasonable to screen athletes after SARS-CoV2 infection with spiroergometry to identify performance limitations and to guide the return to competition.

Effects of surgical face masks on cardiopulmonary parameters during steady state exercise.

Wearing face masks reduce the maximum physical performance. Sports and occupational activities are often associated with submaximal constant intensities. This prospective crossover study examined the effects of medical face masks during constant-load exercise. Fourteen healthy men (age 25.7 ± 3.5 years; height 183.8 ± 8.4 cm; weight 83.6 ± 8.4 kg) performed a lactate minimum test and a body plethysmography with and without masks. They were randomly assigned to two constant load tests at maximal lactate steady state with and without masks. The cardiopulmonary and metabolic responses were monitored using impedance cardiography and ergo-spirometry. The airway resistance was two-fold higher with the surgical mask (SM) than without the mask (SM 0.58 ± 0.16 kPa l-1 vs. control [Co] 0.32 ± 0.08 kPa l-1; p < 0.01). The constant load tests with masks compared with those without masks resulted in a significantly different ventilation (77.1 ± 9.3 l min-1 vs. 82.4 ± 10.7 l min-1; p < 0.01), oxygen uptake (33.1 ± 5 ml min-1 kg-1 vs. 34.5 ± 6 ml min-1 kg-1; p = 0.04), and heart rate (160.1 ± 11.2 bpm vs. 154.5 ± 11.4 bpm; p < 0.01). The mean cardiac output tended to be higher with a mask (28.6 ± 3.9 l min-1 vs. 25.9 ± 4.0 l min-1; p = 0.06). Similar blood pressure (177.2 ± 17.6 mmHg vs. 172.3 ± 15.8 mmHg; p = 0.33), delta lactate (4.7 ± 1.5 mmol l-1 vs. 4.3 ± 1.5 mmol l-1; p = 0.15), and rating of perceived exertion (6.9 ± 1.1 vs. 6.6 ± 1.1; p = 0.16) were observed with and without masks. Surgical face masks increase airway resistance and heart rate during steady state exercise in healthy volunteers. The perceived exertion and endurance performance were unchanged. These results may improve the assessment of wearing face masks during work and physical training.

Effects of surgical and FFP2/N95 face masks on cardiopulmonary exercise capacity.

BACKGROUND: Due to the SARS-CoV2 pandemic, medical face masks are widely recommended for a large number of individuals and long durations. The effect of wearing a surgical and a FFP2/N95 face mask on cardiopulmonary exercise capacity has not been systematically reported. METHODS: This prospective cross-over study quantitated the effects of wearing no mask (nm), a surgical mask (sm) and a FFP2/N95 mask (ffpm) in 12 healthy males (age 38.1 ± 6.2 years, BMI 24.5 ± 2.0 kg/m2). The 36 tests were performed in randomized order. The cardiopulmonary and metabolic responses were monitored by ergo-spirometry and impedance cardiography. Ten domains of comfort/discomfort of wearing a mask were assessed by questionnaire. RESULTS: The pulmonary function parameters were significantly lower with mask (forced expiratory volume: 5.6 ± 1.0 vs 5.3 ± 0.8 vs 6.1 ± 1.0 l/s with sm, ffpm and nm, respectively; p = 0.001; peak expiratory flow: 8.7 ± 1.4 vs 7.5 ± 1.1 vs 9.7 ± 1.6 l/s; p < 0.001). The maximum power was 269 ± 45, 263 ± 42 and 277 ± 46 W with sm, ffpm and nm, respectively; p = 0.002; the ventilation was significantly reduced with both face masks (131 ± 28 vs 114 ± 23 vs 99 ± 19 l/m; p < 0.001). Peak blood lactate response was reduced with mask. Cardiac output was similar with and without mask. Participants reported consistent and marked discomfort wearing the masks, especially ffpm. CONCLUSION: Ventilation, cardiopulmonary exercise capacity and comfort are reduced by surgical masks and highly impaired by FFP2/N95 face masks in healthy individuals. These data are important for recommendations on wearing face masks at work or during physical exercise.

"Pure" severe aortic stenosis without concomitant valvular heart diseases: echocardiographic and pathophysiological features.

PURPOSE: In echocardiography the severity of aortic stenosis (AS) is defined by effective orifice area (EOA), mean pressure gradient (mPGAV) and transvalvular flow velocity (maxVAV). The hypothesis of the present study was to confirm the pathophysiological presence of combined left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and pulmonary artery hypertension (PAH) in patients with "pure" severe AS. METHODS AND RESULTS: Patients (n = 306) with asymptomatic (n = 133) and symptomatic (n = 173) "pure" severe AS (mean age 78 ± 9.5 years) defined by indexed EOA < 0.6 cm2 were enrolled between 2014 and 2016. AS patients were divided into 4 subgroups according to mPGAV and indexed left ventricular stroke volume: low flow (LF) low gradient (LG)-AS (n = 133), normal flow (NF) LG-AS (n = 91), LF high gradient (HG)-AS (n = 21) and NFHG-AS (n = 61). Patients with "pure" severe AS showed mean mPGAV of 31.7 ± 9.1 mmHg and mean maxVAV of 3.8 ± 0.6 m/s. Only 131 of 306 patients (43%) exhibited mPGAV > 40 mmHg and maxVAV > 4 m/s documenting incongruencies of the AS severity assessment by Doppler echocardiography. LVH was documented in 81%, DD in 76% and PAH in 80% of AS patients. 54% of "pure" AS patients exhibited all three alterations. Ranges of mPGAV and maxVAV were higher in patients with all three alterations compared to patients with less than three. 224 (73%) patients presented LG-conditions and 82 (27%) HG-conditions. LVH was predominant in NF-AS (p = 0.014) and PAH in LFHG-AS (p = 0.014). Patients' treatment was retrospectively assessed (surgery: n = 100, TAVI: n = 48, optimal medical treatment: n = 156). CONCLUSION: In patients with "pure" AS according to current guidelines the presence of combined LVH, DD and PAH as accepted pathophysiological sequelae of severe AS cannot be confirmed. Probably, the detection of these secondary cardiac alterations might improve the diagnostic algorithm to avoid overestimation of AS severity.

Alirocumab efficacy and safety by body mass index: A pooled analysis from 10 Phase 3 ODYSSEY trials.

AIMS: Increased body mass index (BMI) contributes to cardiovascular risk and may influence efficacy of therapeutic antibodies. We investigated the effect of baseline BMI on efficacy and safety of alirocumab, a PCSK9 monoclonal antibody. METHODS: In a post-hoc analysis, data were pooled from 10 Phase 3 trials (n=4975) of alirocumab vs. placebo/ezetimibe controls. Alirocumab dose was 150mg every 2 weeks in two trials, and 75mg every 2 weeks with possible increase to 150mg at 12 weeks (based on Week 8 low-density lipoprotein cholesterol [LDL-C]) in eight trials. Efficacy/safety data were assessed in baseline BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2. RESULTS: Baseline LDL-C levels were lower among patients in the higher BMI subgroups. Significant LDL-C reductions from baseline were observed at Weeks 12 and 24 for alirocumab vs. controls, of similar magnitude regardless of baseline BMI (interaction P-value=0.7119). LDL-C<1.81mmol/L (<70mg/dL) was achieved at Week 24 by 69.8-76.4% of alirocumab-treated patients and 9.7-18.4% of control-treated patients, with no pattern by BMI. A greater proportion of patients in higher vs. lower BMI subgroups required alirocumab dose increase (P=0.0343); proportions were 22.5%, 24.9%, 31.7%, and 27.2% of patients across BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2, respectively. Adverse event frequencies were similar regardless of BMI; injection-site reaction frequency was higher with alirocumab (5.1-8.2% across BMI categories) vs. controls (3.6-4.8%). CONCLUSIONS: Alirocumab provided consistent LDL-C reductions, with similar safety findings across BMI subgroups.

[European dyslipidemia guidelines 2019 : What is new?] / Europäische Leitlinien zu Lipiden 2019 : Was ist neu?

In August 2019 the updated dyslipidemia guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were published. Since the last version from 2016, important large randomized trials especially with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and new genetic analyses have become available that show additional reduction of atherosclerotic cardiovascular disease (ASCVD) risk on top of the previously recommended treatments. Based on these data the main concept of the recommendations is achieving an early and as large as possible absolute reduction of low-density lipoprotein cholesterol (LDL-C). As a result of this knowledge and the extended pharmaceutical treatment options the LDL­C goals are amended to lower values. Patients at very high cardiovascular risk are recommended to achieve LDL­C <1.4 mmol/l (55 mg/dl). For patients with high, moderate, and low cardiovascular risks, LDL­C goals are set at <1.8 mmol/l (70 mg/dl), <2.6 mmol/l (100 mg/dl) and <3.0 mmol/l (116 mg/dl), respectively. A new classification of patients with recurrent cardiovascular events despite maximum tolerated statin-based therapy is introduced. For these patients the LDL­C goal is <1.0 mmol/l (40 mg/dl). Novel recommendations comprise a more precise classification of patients at low or moderate risk based on cardiovascular imaging, recommendations for familial hypercholesterolemia, screening for increased lipoprotein(a) and determination of apolipoprotein B as diagnostic and therapeutic goal.

[Management of different cardiovascular risk factors with a combination tablet (polypill)]. / Management verschiedener kardiovaskulärer Risikofaktoren mit einem Kombinationspräparat ("Polypill").

BACKGROUND: The multifactorial origin of cardiovascular diseases has led to polypharmacy in primary and secondary prophylaxis with evidence-based medications, such as statins, antihypertensive drugs and platelet aggregation inhibitors. The number of prescribed drugs correlates inversely to adherence and can lead to treatment failure. Fixed-dose combination drugs (polypills) could increase the medication adherence of patients, reduce risks and prevent cardiovascular events. METHODS: This review is based on publications that were retrieved from Medline (via PubMed) and The Cochrane Library. The clinical database ClinicalTrials.gov. was also considered. RESULTS: In the studies on primary prevention conducted to date, fixed-dose combinations showed a superior control of risk factors, e.g. hypertension and low-density lipoprotein (LDL) cholesterol compared to placebo and at least non-inferiority compared to usual care. In secondary prevention, the effect of the polypill is mostly on the reduction of blood pressure and LDL cholesterol in non-adherent patients; however, evidence that fixed-drug combinations reduce cardiovascular morbidity and mortality compared to standard therapy is lacking. CONCLUSION: The polypill can be considered as an alternative to polypharmacy after a risk-benefit assessment, especially in non-adherent patients. Ongoing studies are investigating the effect of the polypill on cardiovascular events. Current polypills are limited by the lack of sufficient dosages of the individual components to avoid overtreatment and undertreatment at the individual treatment level.

Food supplementation with rice bran enzymatic extract prevents vascular apoptosis and atherogenesis in ApoE-/- mice.

PURPOSE: Atherosclerosis is associated with reduced mononuclear cell (MNC) telomere length, and senescent cells have been detected in atherosclerotic plaques. Rice bran is a source of γ-oryzanol, phytosterols and tocols with potential lipid-lowering, antioxidant and anti-inflammatory activities. Here, we tested the hypothesis that rice bran enzymatic extract (RBEE) impacts on apoptosis, telomere length and atherogenesis in mice. METHODS: Seven-week-old male ApoE-/- mice were fed high-fat diet (HFD) or isocaloric HFD supplemented with 5 % (w/w) RBEE for 23 weeks. Wild-type mice of the same age were kept under standard diet as controls. RESULTS: RBEE treatment reduced total cholesterol (19.24 ± 1.63 vs 24.49 ± 1.71 mmol/L) and triglycerides (1.13 ± 0.18 vs 1.75 ± 0.22 mmol/L) and augmented HDL-cholesterol (1.86 ± 0.20 vs 1.07 ± 0.20 mmol/L). RBEE attenuated macrophage infiltration by 56.69 ± 4.65 % and plaque development (7737 ± 836 vs 12,040 ± 1001 µm2) in the aortic sinus. In the aorta, RBEE treatment reduced expression of the apoptosis pathway components p16, p53 and bax/bcl-2 ratio. RBEE prevented apoptosis of aortic endothelial cells (2.81 ± 0.71-1.14 ± 0.35 apoptotic nuclei/ring for ApoE-/- HFD and ApoE-/- HFD 5 % RBEE, respectively). In contrast, MNC of RBEE-fed mice exhibited enhanced apoptosis marker expression with increased p53 and bax/bcl-2 protein levels. Compared to WT, ApoE-/- mice on HFD were characterized by significant telomere shortening in aorta (11 ± 2 %) and MNC (73 ± 7 %), which was reduced by supplementation with RBEE (aorta: 40 ± 7 %; MNC: 105 ± 10 %). Expression of telomere repeat-binding factor 2 was increased in RBEE-fed mice. CONCLUSION: Long-term food supplementation with RBEE lowers cholesterol and prevents atherosclerotic plaque development in ApoE-/- mice. Differential regulation of vascular and MNC apoptosis and senescence were identified as potential mechanisms.

[Clinical importance of HDL cholesterol]. / Klinische Bedeutung des HDL-Cholesterins.

BACKROUND: Each year 16-17 million determinations of high-density lipoprotein cholesterol (HDL-C) are conducted and interpreted in Germany. Recently acquired data have led to a fundamental reassessment of the clinical significance of HDL-C. METHOD: This review article is based on a selective literature search. RESULTS: Low HDL­C levels usually indicate an increased cardiovascular risk, particularly in primary prevention but the epidemiological relationship between HDL­C and the risk is complex. The HDL plays a role in the back transport and excretion of cholesterol; however, the biological functions of HDL are dependent on the protein and lipid composition, which is not reflected by the HDL­C concentration. If the composition of HDL is pathologically altered it can also exert negative vascular effects. CONCLUSION: Compared with low-density lipoprotein cholesterol (LDL-C), HDL­C is of secondary importance for cardiovascular risk stratification and the calculation of the LDL-C:HDL­C ratio is not useful for all patients. Low HDL­C levels should prompt a search for additional metabolic and inflammatory pathologies. An increase in HDL­C through lifestyle changes (e.g. smoking cessation and physical exercise) has positive effects and is recommended; however, HDL­C is currently not a valid target for drug therapy.

Do patients with diabetes type 2 or chronic heart failure understand a medication plan?

A standardized medication plan (MP) was recently enacted into German law (§ 31a SGB V). The purpose of our study was to assess if patients with chronic diseases requiring polymedication understand the standardized MP and can transfer the given information into practice. 100 patients who took at least five medicines regularly were prospectively included in a cross-sectional study: 50 patients with the primary diagnosis chronic heart failure (CHF), and 50 with diabetes mellitus type 2 (DMT2). We performed a structured test-scenario studying the handling of a provided MP then evaluated the execution of the information on the MP by filling pill boxes and requested patients' opinion. An established weighted scoring system, the "Evaluation Tool to test the handling of the Medication Plan" (ET-MP) was applied to quantitate the ability of the patients to handle the MP. In addition, signs of depression, cognitive function and self-care behavior in chronic heart failure were characterized using the PHQ-9, Mini-Cog, and G9-EHFScB-9 questionnaires, respectively. The understanding of the MP was poor and irrespective of the underlying primary diagnosis. Only 32% of all patients were able to handle the MP without difficulties (ET-MP score >90%), the median ET-MP score was 83 [(IQR) 50-98]. Comprehension of the MP was better in patients aged <70 years compared to ≥70 years (p<0.01). Patients ≥10 years of education achieved higher ET-MP results than patients with <10 years of education (p<0.01). Patients with signs of cognitive impairment exhibited significantly lower ET-MP scores than patients without cognitive impairment (p<0.001). There were no significant correlations of the ET-MP score with number of daily medications, living situation, sex, the Charlson Comorbidity Index, the PHQ-9 score, and use of a dosing aid or possession of a medication list.

[PCSK9 inhibitors : Recommendations for patient selection]. / PCSK9-Inhibitoren : Empfehlungen zur Patientenauswahl.

The 2 or 4­week subcutaneous therapy with the recently approved antibodies alirocumab and evolocumab for inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces low-density lipoprotein cholesterol (LDL-C) in addition to statins and ezetimibe by 50-60 %. The therapy is well-tolerated. The safety profile in the published studies is comparable to placebo. Outcome data and information on long-term safety and the influence on cardiovascular events are not yet available but the results of several large trials are expected in 2016-2018. At present (spring 2016) PCSK9 inhibitors represent an option for selected patients with a high cardiovascular risk and high LDL-C despite treatment with the maximum tolerated oral lipid-lowering therapy. This group includes selected patients with familial hypercholesterolemia and high-risk individuals with statin-associated muscle symptoms (SAMS).

Mitochondrial regulation of reactive oxygen species (ROS) production-Unexpected observations in early postnatal cerebral vasculature.

Nicotinamide-nucleotide-transhydrogenase (Nnt) is a mitochondrial protein. It is altered and functionally lacking in the C57BL/6J sub-strain. This leads to the generation of more radical oxygen species than in the C57BL/6N sub-strain. During studies on the effect of Nnt in perinatal hypoxia the cerebral vasculature was investigated in postnatal day 9 mice using post mortem arterial filling with silicone rubber compounds. Surprisingly, the tiny vessels were no longer uniformly filled and a bleb-like pattern occurred in both sub-strains. Furthermore, considerably more bleb-like spots were observed in the C57Bl/6J sub-strain than in the C57Bl/6N sub-strain. These blebs might be the result of feathery vessels bursting. It remains unclear how the mechanisms in the used strains differ. Nnt might influence the vascular structure or its development and mechanisms and should be investigated further.

[Poor medication adherence and worsening of heart failure--a vicious circle]. / Chronische Herzinsuffizienz: Teufelskreis aus geringer Einnahmetreue von Medikamenten und kardialer Dekompensation.

Despite of markedly improved options for treatment, chronic heart failure is associated with recurrent worsening of symptoms. Poor medication adherence has adverse effects on frequency and progression of congestive heart failure. There are three relevant areas of problems that could be aggravated by each other:There is the problem of changes in pharmacokinetics in worsening heart failure. Proportional to the severity of heart failure, there is an existing intestinal edema and changes of intestinal bacterial colonization that may affect a drug's absorption and, hence, its efficacy.Depression and impaired cognitive function is quite common in patients with chronic heart failure. Depression both predicts hospitalization and mortality rate as well as poor medication adherence in CHF. Compared to stable CHF patients, cognitive function deteriorates significantly while decompensation leading to impaired medication adherence.Shown by recent studies, there is a higher risk for poor medication adherence after a cardiovascular event.Poor medication adherence is associated with an increased rate of cardiovascular events not only in heart failure, but also in all cardiovascular diseases. Hence, there is a need for specific and long term interventions to improve medication adherence at an early stage.