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Background/Introduction The Global SYMPLICITY Registry (GSR) was designed to evaluate the safety and efficacy of renal denervation (RDN) in real-world patients. Inclusion and exclusion criteria are limited to allow assessment of the effects of RDN on patients with a wide range of comorbidities. The current analysis examines blood pressure (BP) reduction after RDN in higher cardiovascular risk patients. Purpose To evaluate blood pressure reduction after RDN in higher cardiovascular risk patients in GSR. Methods GSR is a prospective all-comers registry to evaluate the safety and efficacy of RDN. Patients are enrolled in GSR and receive radiofrequency RDN using the Symplicity Flex or Symplicity Spyral catheter. Office and ambulatory BP are measured at each follow-up (3, 6, 12, 24, and 36 months). In this post-hoc analysis, changes from baseline in office and 24-hour ambulatory systolic blood pressure were assessed in patients at higher cardiovascular risk. Higher risk was defined using baseline office systolic or diastolic BP as well as additional risk factors (Figure 1). Results As of March 2021, there were 2621 patients characterized as higher cardiovascular risk in GSR. Baseline characteristics included mean age 60.7±12.1 years, 57.6% male, 37.9% type 2 diabetes, 35.8% hypocholesterolemia, 19.7% eGFR Conclusions Higher risk patients in GSR had sustained office and ambulatory systolic BP reductions out to 3 years after catheter-based radiofrequency RDN. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic

AimsEnd-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and resultsThe AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.ConclusionsOur findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Type B aortic dissection is a relatively rare clinical picture that involves many fields of medicine and requires a multidisciplinary approach. In this report, the disciplines involved constitute the most important aspects of the new S2k guidelines for the diagnosis and treatment of type B aortic dissection. More specifically, the definition and epidemiology, the clinical and technical diagnostic methods, in addition to the imaging methods, are presented, and recommendations for the individual topics based on scientific studies and expert opinion are given. In the guidelines, the various procedures related to the main conservative and surgical treatment regimes in the acute, subacute, and chronic phases of the condition are dealt with.

Die Typ-B-Aortendissektion ist ein relativ seltenes Krankheitsbild, welches in sehr vielen Bereichen der Medizin vorkommt und einen interdisziplinaren Behandlungsansatz erfordert. Die beteiligten Disziplinen stellen in diesem Beitrag die wesentlichen Aspekte der neuen S2k-Leitlinie zur Diagnostik und Therapie der Aortendissektion Typ B dar. Im Einzelnen werden die Definition und Epidemiologie, die klinische und instrumentelle Diagnostik sowie die bildgebenden Verfahren dargestellt und zu den einzelnen Themen aufgrund von wissenschaftlichen Studien und Expertenmeinung Empfehlungen gegeben. In der Leitlinie wird auserdem auf die unterschiedlichen Vorgehensweisen in Bezug auf primar konservative und operative Therapieregime in der akuten, subakuten und chronischen Phase der Erkrankung eingegangen.

In a 47-year-old man with non-Hodgkin's lymphoma which had been treated by polychemotherapy and radiation, cardiac involvement was suspected on computed tomography (CT) two years after diagnosis. The ECG demonstrated atrial flutter and a slow ventricular rate. After a further cycle of chemotherapy the patients declined further treatment. Two years later he was admitted urgently because of cardiac failure, atrial fibrillation with a slow ventricular rate, and clear signs of abnormal repolarization. CT of the thorax again provided signs of cardiac involvement with lymphoma. In addition there were extensive tumour infiltrates in the liver and paraaortic lymph-node. Despite intensive medical treatment he died shortly after admission from cardiac failure. At necropsy all four cardiac chambers and the coronary arteries were surrounded completely by tumour tissue. The membranous interventricular septum, the area of the Hiss bundle and the tricuspid and mitral valves had also been infiltrated. Histologically the infiltrates consisted of lymphoid cells of centrocytic type. Increasing tumour cell involvement went together with complete disintegration of myocardial fibres.

The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in-class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions.The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen.Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non-RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non-RAS; p0.0001).In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting.

One of the major unintended consequences of Acquisition Reform efforts during the 1990s was a reduction in rigor of sustainment planning and effectiveness throughout materiel development programs. As the evidence of this problem mounted over the past decade, the Department of Defense (DoD) initiated efforts to rejuvenate sustainment planning during the early phases of program development. This article provides brief descriptions of the actions that have been taken, or that are being planned, to achieve this goal.

Highly charged Ar (up to 18+), Xe (up to 48+), and U (up to 71+) ions produced through electron-impact ionization and excitation in an electron-beam ion trap have efficiently been extracted from the trap, and mass and charge analyzed. Charge-state distributions for Ar and Xe ions following electron-impact ionization and excitation have been measured. Relative yields for the production of Ar{sup 16+} and Xe{sup 44+} ions have been deduced as a function of electron-beam energies. Ar {ital K} and Xe {ital L} x-ray emission following Ar{sup 17+}, Ar{sup 18+} and Xe{sup 44+}, Xe{sup 45+} and Xe{sup 48+} ion impact on a Cu surface was measured. The observed line positions demonstrate electron capture into high-{ital n} states and a fast radiative decay in the neutralization process at the surface.

Antihypertensive drugs, recommended by the World Health Organization for use in monotherapy, exert different effects on glucose and lipid metabolism. In our study we compared the effects of the beta-blocker atenolol (AT) and the alpha1-blocker bunazosin (BU) on glucose metabolism. The doses administered were chosen to produce similar antihypertensive effects with both drugs. The study was conducted as a bicenter, parallel, controlled, and double-blind study. All patients suffered from mild to moderate primary hypertension, were obese (body mass index26 kg/m2), but were nondiabetic. After a drug-free period of 4 weeks, patients were treated either with 6 and 12 mg of bunazosin (n = 15) or with 50 and 100 mg of atenolol (n = 17) once daily for 12 weeks. Glucose metabolism was measured by the iv glucose tolerance test (GTT) and the euglycemic hyperinsulinemic clamp test. The results show a similar blood pressure reduction with both drugs. However, their effects on glucose metabolism were significantly (p0.05) different: The area under the curve (AUC) of glucose in the iv GTT increased 26.8% during atenolol treatment but decreased 30% during bunazosin treatment. The same influence on the AUC of insulin was observed [AT +478.5 +/- 441.8 (+22%) vs. BU, -588.5 +/- 411.1 (-22%)]. Similar changes were found in the glucose clamp test. The metabolic clearance rate increased 11.4% during bunazosin use and decreased 8.4% during atenolol use to the same degree that the insulin sensitivity index changed (BU +13.2% vs. AT -21.9%). The differences between the two treatment regimes were statistically significant (p0.05). These results in obese hypertensives confirm the well-known negative effects of beta-blockers on glucose metabolism. Additionally, they demonstrate that an alpha1-blocker such as bunazosin develops the same blood pressure-lowering effect as beta-blockers, but with a significantly better profile with regard to glucose metabolism. Therefore, the use of alpha1-blockers can be recommended for obese hypertensives without any special care for glucose metabolism.

Die Pravalenz der arteriellen Hypertonie liegt zwischen 15 und 20%. Epidemiologische Untersuchungen konnten zeigen, das eine direkte Beziehung zwischen der Hohe des Blutdrucks und der kardiovaskularen Morbiditat und Mortalitat besteht [81,156]. Umgekehrt gilt, das eine Senkung eines erhohten Blutdrucks mit einer Reduktion kardiovaskularer Komplikationen einhergeht. Als eine der ersten klinisch kontrollierten Untersuchungen konnte die Veterans Administration Study nachweisen, das bei Patienten mit schwerer arterieller Hypertonie eine antihypertensive Therapie zu einer signifikanten Abnahme der kardiovaskularen Mortalitat fuhrte [178]. Wahrend in dieser Untersuchung nur Patienten mit einem diastolischen Blutdruck ≥ 115 mmHg behandelt wurden, liegen inzwischen Ergebnisse vieler multizentrischer klinischer Untersuchungen bei insgesamt uber 40000 Patienten vor, die eine Reduzierung der hypertonieassoziierter kardiovaskularer Morbiditat und Mortalitat bei der milden arteriellen Hypertonie (diastolischer Blutdruck 90–104 mmHg) und bei der masigen arteriellen Hypertonie (diastolischer Blutdruck 105–114 mmHg) nachwiesen [42,65,75,114,126,170,178,179].

Zwei Varianten einer dreistufigen Synthese von Crocetin-dimethylester (1c) werden beschrieben. 2,6-Dimethylphenol (2a) oder 4-Brom-2,6-dimethylphenol (2b) und (E)-1,4-Dibrom-2-buten (3a) dienen als bequem zugangliche Synthesebausteine. Die photochemische Offnung der linearkonjugierten Cyclohexadienone 6 und 7 zu seco-isomeren Dienylketenen, die mit Frankfurter Sonnenlicht muhelos erreicht werden kann, spielt die Schlusselrolle. Die Konfiguration der stereoisomeren Schlusselverbindungen 6 und 7 wird durch enantioselektiven Abbau von 7 mit zirkular polarisiertem Licht sowie durch enantioselektiven Aufbau von 7 festgelegt. Light-induced Reactions, XII. A Convenient Synthesis of Dimethylcrocetin Two variant schemes of a three-step synthesis of crocetin dimethyl ester (1c) are described. 2,6-Dimethylphenol (2a) or 4-bromo-2,6-dimethylphenol (2b), respectively, and (E)-1,4-dibromo-but-2-ene (3a) serve as conveniently available starting material. The photochemical cleavage of the linearly conjugated cyclohexadienones 6 and 7 affording seco-isomeric dienyl ketenes plays the key role, and is smoothly achieved by sun light of Frankfurt. The configuration of the stereoisomeric key compounds 6 and 7 is determined by enantioselective degradation, using circularly polarized light, as well as by enantioselective synthesis of 7.

The influence of beta blockers on Type A behavior pattern and cardiovascular reactivity was tested. Nineteen white, male hypertensive patients were divided at random into two therapeutic groups (100 mg atenolol versus 50 mg hydrochlorothiazide + 5 mg amiloride (control group) ). For each patient, the German version of the structured interview was performed before therapy and at a minimum of 4 weeks after normalization of clinical resting casual blood pressure (BP). Prior to therapy, there were no differences in age, BP at rest, cardiovascular reactivity, and Type A between the two groups. After therapy, the patients treated with beta blockers changed Type A characteristics toward Type B, regardless where they started on the Type A scale, and beta blockers attenuated cardiovascular reactivity. In this study, Type A (hypertensive patients) was not associated with greater cardiovascular reactivity.

Mit Hilfe storungstheoretischer Argumente, der erweiterten Huckel-Methode und ab initio-Berechnungen (Gaussian 70) wird ein MO-Modell fur die SN2-Reaktion mit Retention abgeleitet, das einen streng konzertierten Mechanismus mit ausschlieslichem Konfigurationserhalt am Substitutionszentrum fordert. Die fur die SN2-Reaktion mit Retention notwendigen Voraussetzungen werden diskutiert. A MO Model for the SN2-Reaction with Retention Qualitative MO-arguments, extended Huckel calculations and ab initio calculations (Gaussian 70) are utilized to develop a MO-model for the SN2-reaction with retention. This model supports a strictly concerted mechanism occuring exclusively with retention. The factors responsible for the SN2-reaction with retention are discussed.

On Dien-Ketenes from o-Quinol-Acetates A detailed picture of the photochemistry of o-quinol-acetates is presented. (RS)-6-Acetoxy-6-methyl-, (RS)-6-acetoxy-2,6-dimethyl-, (RS)-6-acetoxy-5,6-dimethyl-, (RS)-6-acetoxy-2,4,6-trimethyl-, (RS)-6-acetoxy-2,3,4,6-tetramethyl-, and (RS)-6-acetoxy-2,3,4,5,6-pentamethyl-2,4-cyclohexadien-1-ones serve as representative educts. There are two separate main photochemical routes conveniently designated as 1(π*, n) or 3(π*, π) tracks. The latter may also be attained by sensitization and leads to phenols. The former, by α-cleavage furnishes dienketens as indispensable phototransients. Photolysis of dien-ketens follows one or more of three reaction channels, each of which yields a particular type of photoproduct: heat-induced monocyclization affords 2,4-cyclohexadien-1-ones, heat-induced bicyclization stereoselectively furnishes bicyclo[3.1.0]hex-3-en-2-ones, and multi-step addition of protic nucleophiles stereoselectively gives 1,4-, 1,6- and/or 1,2-adducts. By X-ray analysis or NOE studies, the structure of isolated photoproducts is established. Conventional spectroscopy at low or flash spectroscopy at normal temperature yield information on the formation and decay of kinetically unstable intermediates. Photoproduct composition depends on the pattern of substitution of the educts, on the solvents, and on the nucleophiles that might be present. Substituents primarily exert an influence upon the population of the various conformers of the dien-keten. Solvents affect the rate of the divers reaction paths competing for the phototransient. Nucleophiles play more than a trivial role when adducts are formed. With the detailed view of a dien-keten's role on hand, the photoproduct from a given o-quinol-acetate or more general from a linear conjugated cyclohexadienone is now predictable.

To evaluate the role of the sympathetic nervous system in essential hypertension and the influence of clonidine, 28 male subjects with mild to moderate hypertension were either treated with low-dose clonidine (n = 14, mean age: 42.4 +/- 2.1 years) or were randomized to a nontreated control group (n = 14, mean age: 40.2 +/- 2.4 years). Clinical blood pressure and heart rate were assessed, and after 4 weeks of treatment plasma catecholamines and the hemodynamic response to mental arithmetic, cold stimulation, and ergometric exercise were compared between both groups. Under therapy with 0.075 mg of clonidine per day casual blood pressure dropped and diastolic BP was significantly lower than in the control group. Heart rate did not change. After 4 weeks the plasma levels of epinephrine and norepinephrine were the same in both groups. During mental arithmetic total peripheral resistance decreased in the treated group while it did not change in the control group, but both groups did not differ in their percentage changes in the hemodynamic parameters in response to the three stress tests. It has been concluded that clonidine reduces sympathoadrenergic activity, but in a low dosage this effect is obviously restricted to a reduction of arteriolar tone.

To study the phenomenon of cardiovascular hyperreactivity it is essential to know the impact of stimulus intensity and the effects induced by repeated exposure to a stressful situation like a mental arithmetic task. All subjects in this study were young healthy male students. Two different mental stressors were used: a mental arithmetic task with low stimulus intensity and one with high stimulus intensity characterised by more challenging instructions, a more competitive situation, and exposure to affective noise. The lower level mental test did not disclose any differences in the hemodynamic response in the subjects. Only the mental stress test with high stimulus intensity proved capable of detecting the cardiovascular hyperreactivity in normotensive subjects with familial hypertension. As hemodynamic response was attenuated during the second mental stress test if the second test was the lower stimulus test, and since repeated stress testing is necessary when prospective or intervention studies are performed, the stimulus intensity and sequence of mental stress tests had to be controlled carefully. To counteract any cardiovascular adaptation, it is suggested that the stimulus intensity of mental stress tests should slightly increase when repeatedly applied.

We compared the blood pressure (BP) of 61 healthy male Ss during mental arithmetic plus noise, physical exercise testing and the Type A interview. A consistent association between personality characteristics and cardiovascular reactivity was not found. There was a consistent correlation between systolic BP reactivity during mental arithmetic and the Type A interview. Mental arithmetic and exercise testing correlated significantly for middle aged men. No correlation of BP was found between the Type A interview and exercise testing.

The influence of beta blockers on Type A behavior pattern and cardiovascular reactivity was tested. Nineteen white, male hypertensive patients were divided at random into two therapeutic groups (100 mg atenolol versus 50 mg hydrochlorothiazide + 5 mg amiloride (control group) ). For each patient, the German version of the structured interview was performed before therapy and at a minimum of 4 weeks after normalization of clinical resting casual blood pressure (BP). Prior to therapy, there were no differences in age, BP at rest, cardiovascular reactivity, and Type A between the two groups. After therapy, the patients treated with beta blockers changed Type A characteristics toward Type B, regardless where they started on the Type A scale, and beta blockers attenuated cardiovascular reactivity. In this study, Type A (hypertensive patients) was not associated with greater cardiovascular reactivity.

The effects of baseline antihypertensive drugs or sympatholytic agents on the characteristic hemodynamic response pattern (i.e. increase in blood pressure and heart rate, decrease in total peripheral resistance) during emotional stress were examined. Middle aged male caucasian patients with hitherto untreated mild essential hypertension were given nitrendipine 10-20 mg per day, oxprenolol 160 mg per day or clonidine 75-300 micrograms per day until casual blood pressure was below 140/90 mmHg for at least three months. Blood pressure, heart rate and stroke volume was assessed, at rest and during emotional stress, before and during effective antihypertensive therapy. The increase in systolic pressure during stress was not attenuated by any of the drugs. Heart rate reactivity was lowest when patients received oxprenolol, but peripheral resistance during emotional stress was significantly increased. Clonidine had no unfavorable effects on the hemodynamic pattern during emotional stress but nitrendipine decreased peripheral resistance even more than the decrease in resistance observed during stress before initiation of therapy. If one accepts that antihypertensive therapy should not alter a physiological hemodynamic pattern to an unphysiological response, psychophysiological examinations seem to be valid in selecting suitable patients for the different alternatives in antihypertensive therapy.