Statin loading before coronary artery bypass grafting: a randomized trial.

AIMS: Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. METHODS AND RESULTS: This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74-1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69-1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

Acute Chest Pain­Diagnostic Accuracy and Pre-Hospital Use of Anticoagulants and Platelet Aggregation Inhibitors

BACKGROUND: Acute chest pain (aCP) can be a symptom of life-threatening diseases such as acute coronary or aortic syndrome, but often has a non-cardiac cause. The recommendations regarding pre-hospital drug treatment of patients with aCP are ambiguous. METHODS: A retrospective cohort study was conducted of 822 patients with aCP who were attended by emergency physicians. The cause of aCP was classified as follows: acute coronary syndrome without ST-segment elevation (NSTE-ACS), acute aortic syndrome, hypertensive crisis, cardiac arrhythmias, musculoskeletal, or other. The suspected and discharge diagnoses were compared, and the pre-hospital administration of acetylsalicylic acid (ASA) and unfractionated heparin (UFH) was analyzed. Furthermore, the parameters that improved diagnostic accuracy were investigated. RESULTS: The positive predictive value of the diagnosis assigned by the emergency physician (EP diagnosis) was 39.7%. NSTEACS was the most commonly suspected cause of aCP (74.7%), but was confirmed after hospital admission in only 26.3% of patients. ASA was administered in 51%, UFH in 55%, and both substances in 46.4% of cases. A large proportion of patients received anticoagulants in the pre-hospital setting although the discharge diagnosis was not NSTE-ACS: ASA 62.9%, UFH 66.0%, both substances 56.5%. CONCLUSION: ASA and UFH are often given to EP-accompanied patients with aCP despite the low accuracy of diagnosis in the pre-hospital setting. Pre-hospital measurement of high-sensitivity troponin T (hs Trop-T) might improve discrimination between NSTE-ACS and other causes of aCP. This is important, as the current guidelines contain no clear recommendations for prehospital drug treatment in NSTE-ACS.

Cardiopulmonary function during exercise in heart failure with reduced ejection fraction following baroreflex activation therapy.

PURPOSE: Baroreflex activation therapy has favorable effects in heart failure patients. We report the results of a single-center study of baroreflex activation therapy in heart failure with reduced ejection fraction including cardiopulmonary exercise testing for the first time to show the effect on exercise capacity. METHODS: A total of 17 patients were treated with baroreflex activation therapy. Eligibility criteria were the New York Heart Association class ⩾III and ejection fraction ⩽35% on guideline-directed medical and device therapy. The New York Heart Association class, quality of life, and 6-min hall walk distance were assessed in all patients. Twelve patients underwent cardiopulmonary exercise testing before and 8.9 ± 6.4 months after initiation of baroreflex activation therapy. RESULTS: The New York Heart Association class and 6-min hall walk distance improved after baroreflex activation therapy, while quality of life remained stable. Weight-adapted peak oxygen uptake increased significantly from 10.1 (8.2-12.9) ml/min/kg to 12.1 (10.4-14.6) ml/min/kg (p = 0.041). Maximal heart rate was stable. Maximal oxygen pulse increased from 9.7 (5.5-11.3) to 9.9 (7.1-12.1) ml/heartbeat (p = 0.047) in 10 patients with low maximal oxygen pulse at baseline (<16.5 ml/heartbeat). There was no significant change in maximal oxygen pulse in the whole cohort. Ventilatory efficiency remained stable. CONCLUSION: Weight-adapted peak oxygen uptake improved after baroreflex activation therapy, pointing to an enhanced exercise capacity. Ventilatory efficiency and heart rate did not change, while oxygen pulse increased in patients with low oxygen pulse at baseline, indicating an improvement in circulatory efficiency, that is, a beneficial effect on stroke volume and peripheral oxygen extraction.

Nodular Lymphoid Hyperplasia as Incidental Finding of Suspect Pulmonary Mass.

Nodular lymphoid hyperplasia of the lung is a rare disease of polyclonal lymphoid proliferation. The incidental finding of a solid nodular lesion with irregular margins adjacent to the visceral pleura in the reported case was highly suggestive of malignancy. The present report underscores the typical immunohistochemical findings and the benign course of nodular lymphoid hyperplasia. The current knowledge about disease aetiology and the value of different diagnostic tools to distinguish nodular lymphoid hyperplasia from other pulmonary lymphoid lesions are summarized by a review of the literature. Surgical resection is not only diagnostic but also curative with no evidence so far that NLH can regress without operation. The present case shows the spontaneous regression of NLH after CT-guided biopsy indicating that an alternative, less invasive diagnostic approach has curative potential.

The Hypertension Paradox: Survival Benefit After ST-Elevation Myocardial Infarction in Patients With History of Hypertension. A Prospective Cohort- and Risk-Analysis.

Background: Mortality after ST-elevation myocardial infarction (STEMI) is dependent from best-medical treatment after initial event. Objectives: Determining the impact of prescription of guideline-recommended therapy after STEMI in two cohorts, patients with and without history of arterial hypertension, on survival. Methods: 1,025 patients of the Cologne Infarction Model registry with invasively adjudicated STEMI were dichotomized according to their history of arterial hypertension. We recorded prescription rates and dosing of RAS-inhibitors, ß-blockers and statins in all patients. The primary outcome was all-cause death. Mean follow-up was 2.5 years. Results: Mean age was 64 ± 13 years, 246 (25%) were women. 749 (76%) patients had a history of hypertension. All-cause mortality was 24.2%, 30-day and 1-year mortality was 11.3% and 16.6%, respectively. History of hypertension correlated with lower mortality (hazard ratio [HR], @30 days: 0.41 [0.27-0.62], @1 year: 0.37 [0.26-0.53]). After adjusting for age, sex, Killip-class, diabetes mellitus, body-mass index, kidney function and statin prescription at discharge 1-year mortality HR was 0.24 (0.12-0.48). At discharge, prescription rates for RAS-inhibitors, ß-blockers and statins, as well as individual dosing and long-term persistence of RAS-inhibitors were higher in patients with history of hypertension. On the same lines, prescription rates for RAS-inhibitors, ß-blockers and statins at discharge correlated significantly with lower mortality regardless of history of hypertension. Conclusion: Patients with history of hypertension show higher penetration of guideline recommended drug therapy after STEMI, which may contribute to better survival. Better tolerance of ß-blockers and RAS-inhibitors in patients with history of hypertension, not hypertension itself, likely explains these differences in prescription and dosing.

Harmonised LUCAS in-situ land cover and use database for field surveys from 2006 to 2018 in the European Union.

Accurately characterizing land surface changes with Earth Observation requires geo-located ground truth. In the European Union (EU), a tri-annual surveyed sample of land cover and land use has been collected since 2006 under the Land Use/Cover Area frame Survey (LUCAS). A total of 1351293 observations at 651780 unique locations for 106 variables along with 5.4 million photos were collected during five LUCAS surveys. Until now, these data have never been harmonised into one database, limiting full exploitation of the information. This paper describes the LUCAS point sampling/surveying methodology, including collection of standard variables such as land cover, environmental parameters, and full resolution landscape and point photos, and then describes the harmonisation process. The resulting harmonised database is the most comprehensive in-situ dataset on land cover and use in the EU. The database is valuable for geo-spatial and statistical analysis of land use and land cover change. Furthermore, its potential to provide multi-temporal in-situ data will be enhanced by recent computational advances such as deep learning.

How long is long enough? Good neurologic outcome in out-of-hospital cardiac arrest survivors despite prolonged resuscitation: a retrospective cohort study.

BACKGROUND: Despite all efforts, mortality of out of hospital cardiac arrest (OHCA) remains high. Patients with OHCA due to a primary shockable rhythm typically have a better prognosis. However, outcome worsens if return of spontaneous circulation (ROSC) cannot be achieved quickly. There is insufficient evidence for maximum duration of resuscitation in these patients and it is unclear, which patients profit from transport under ongoing CPR. OBJECTIVE: Investigate predictors for favourable neurologic outcome in OHCA patients with presumed cardiac cause due to refractory shockable rhythm (rSR). METHODS: Retrospective analysis of OHCA patients that presented to a tertiary hospital due to a rSR. RESULTS: One hundred seventy-five OHCA patients with presumed cardiac cause due to rSR were included. Overall hospital mortality was 50% and 83% of initial survivors were discharged with a good neurologic outcome [cerebral performance category (CPC) 1-2]. In patients with a time from cardiac arrest to ROSC of > 45 min, 18% survived to CPC 1-2. Independent predictors for good neurologic outcome were age, lower no-flow time and lower serum lactate levels at hospital arrival. CONCLUSION: In an urban setting, a significant proportion of OHCA patients with rSR can survive to a good neurologic outcome, despite very long time to ROSC.

Baroreflex activation therapy reduces frequency and duration of hypertension-related hospitalizations in patients with resistant hypertension.

PURPOSE: Baroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints. METHODS: Patients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies. RESULTS: Records on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 ± 3.5/year before BAT and 2.2 ± 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 ± 1.6/year before BAT to 0.5 ± 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 ± 8.7 days/year before BAT to 1.8 ± 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 ± 27 mmHg over 102 ± 17 mmHg under 6.6 ± 2.0 antihypertensive drugs before BAT and 157 ± 32 mmHg over 91 ± 20 mmHg (both p < 0.01) under 5.9 ± 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 ± 21 mmHg over 91 ± 14 mmHg before BAT and 153 ± 21 mmHg (p = 0.03) over 89 ± 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 ± 16 bpm before BAT and 72 ± 12 bpm at latest follow-up (p = 0.35). CONCLUSIONS: Rate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies.

Malignant Arrhythmias During Induction of Target Temperature Management After Cardiac Arrest.

The aim of this study was to evaluate the incidence and determinants of malignant arrhythmias (MA) in patients with shock following out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management. Risk factors for the development of MA were prospectively analyzed in patients after OHCA. MA were defined as ventricular tachycardia or fibrillation with a duration >30 seconds, which had to be terminated by defibrillation. All patients were treated with therapeutic hypothermia for 24 hours. Demographics, OHCA details, interventions, and intensive care unit (ICU) treatment were recorded. A total of 55 patients were included, 11 (20%) of whom developed MA during the ICU stay. All MA occurred within the first 18 hours after admission. Patients who developed MA showed a stronger decrease in body temperature (Δ -2.4°C ± 0.8°C vs. Δ -1.3°C ± 1.3°C; p = 0.016) and in serum potassium levels (Δ -0.9 ± 1 mmol/L vs. Δ -0.3 ± 0.6 mmol/L; p = 0.037) during the cooling period compared with patients without MA. In the multivariable analysis, fast temperature decline as well as lower potassium levels were associated with MA. In addition, higher number of shocks during resuscitation and higher ICU epinephrine use were independent predictors of MA in patients with OHCA. The use of epinephrine as well as hypokalemia in context with intense cooling may increase the incidence of MA in patients with shock after cardiac arrest. Therefore, these therapeutic strategies should be applied with caution in this vulnerable group of patients.

Efficacy of Electrical Baroreflex Activation Is Independent of Peripheral Chemoreceptor Modulation.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end-tidal O2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO2 and O2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P<0.001), heart rate from 64±13 to 61±13 bpm (P=0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min (P=0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg (P=0.057), heart rate 10±6 bpm (P<0.001), muscle sympathetic nerve activity 7±7 bursts/min (P=0.031), and ventilation 10±7 L/min (P=0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg (P=0.938), heart rate: -2±3 versus -2±2 bpm (P=0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min (P=0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Status of hypertension in Europe.

PURPOSE OF REVIEW: Arterial hypertension is the leading preventable cause of cardiovascular disease worldwide. Effective European programs aiming to improve awareness, treatment, and control of hypertension are lacking. RECENT FINDINGS: Europe is heading the statistics for hypertension prevalence and cardiovascular disease. On the one hand this predominance reflects the increasing life expectancy in European population, whereas on the other hand, it can be attributed to the sedentary lifestyle and the nutritional habits of wealthy societies. Despite its economic power, Europe also ranges among the regions with the lowest rates of hypertension awareness and control worldwide. SUMMARY: The present study discusses the influence of medical inertia, insufficient patient education, contradictory recommendations from the European and independent national societies, the need for hypertension programs, as well as differences in health policies in Europe as potential factors that may contribute to this discrepancy.

What do we really know about supine hypertension in patients with orthostatic hypotension.

PURPOSE OF REVIEW: Patients with severe orthostatic hypotension due to autonomic failure may be hypertensive in the supine position. Until recently, there were no internationally recognized diagnostic criteria for supine hypertension. This review covers diagnostic criteria, mechanisms, and management of supine hypertension in autonomic failure patients. RECENT FINDINGS: Recently, an international consensus group defined supine hypertension in patients with neurogenic orthostatic hypotension as brachial SBP at least 140 mmHg and/or DBP at least 90 mmHg while supine. Using these criteria, a large proportion of patients with orthostatic hypotension is diagnosed with supine hypertension. Recent research supports the concept that the hypertension can be mediated through residual sympathetic nervous system function and independently from sympathetic activity, for example via mineralocorticoid receptor activation. SUMMARY: The clear definition of supine hypertension is an important step that will hopefully foster clinical research in this area. Supine hypertension promotes renal sodium excretion, thus, worsening orthostatic hypotension the next morning. Supine hypertension may promote cardiovascular and renal disease. Yet, long-term benefits of treating supine hypertension be it through non pharmacological or pharmacological means have not been proven by sufficiently large clinical trials.

Management of supine hypertension in patients with neurogenic orthostatic hypotension: scientific statement of the American Autonomic Society, European Federation of Autonomic Societies, and the European Society of Hypertension.

: Supine hypertension commonly occurs in patients with neurogenic orthostatic hypotension due to autonomic failure. Supine hypertension promotes nocturnal sodium excretion and orthostatic hypotension, thus, interfering with quality of life. Perusal of the literature on essential hypertension and smaller scale investigations in autonomic failure patients also suggest that supine hypertension may predispose to cardiovascular and renal disease. These reasons provide a rationale for treating supine hypertension. Yet, treatment of supine hypertension, be it through nonpharmacological or pharmacological approaches, may exacerbate orthostatic hypotension when patients get up during the night. Fall-related complications may occur. More research is needed to define the magnitude of the deleterious effects of supine hypertension on cardiovascular, cerebrovascular, and renal morbidity and mortality. Integration of more precise cardiovascular risk assessment, efficacy, and safety data, and the prognosis of the underlying condition causing autonomic failure is required for individualized management recommendations.

Reliable and easy-to-use LC-MS/MS-method for simultaneous determination of the antihypertensives metoprolol, amlodipine, canrenone and hydrochlorothiazide in patients with therapy-refractory arterial hypertension.

BACKGROUND: Therapy-refractory arterial hypertension is defined as a blood pressure (BP) in a subset of patients who fail to achieve BP control despite a three-drug regimen (including a diuretic). Various factors have impact on loss of therapy response. Drug-drug-interactions (DDIs) may cause altered pharmacokinetics (PK) of antihypertensive drugs. Upregulation of activity and expression of cytochrome P450 (CYP) enzymes can result in decreased plasma drug levels. Besides these PK considerations a significant problem could be nonadherence to drug therapy. In this regard Therapeutic Drug Monitoring (TDM) is a useful tool for detecting nonadherence. Therefore a LC-MS/MS-method for determination of Metoprolol (MET), Amlodipine (AML), Canrenone (CAN) and Hydrochlorothiazide (HCT) was developed. METHODS: An UHPLC-MS/MS method was developed and validated for simultaneous determination of MET, AML, CAN and HCT in plasma matrix. Extraction of serum samples consisted of simple protein precipitation using acetonitrile. Stable isotope labeled analogues for each antihypertensive were obtained for internal standardization and quantitative analysis ([2H7]-MET, ([13C6]-AML, [2H4]-CAN, [13C6]-HCT). Calibrators and quality controls were prepared in plasma matrix of normal individuals. Sample preparation: protein precipitation with acetonitrile and addition of internal standard-mix. RESULTS: All analytes were eluted within a runtime of 2.5 min. Linearity experiments were demonstrated in plasma over following concentration ranges: MET: 5-750 µg/l, AML: 1-50 µg/l, CAN: 10-500 µg/l, HCT: 5-500 µg/l (R2 > 0.993). Chromatographic separation was achieved using a C18 column (50 × 2.1 mm, 1.9 µm particle size) and an isocratic elution. LC-MS/MS analyses were performed on a triple quadrupole mass spectrometer using positive and negative electrospray ionization in selected reaction monitoring (SRM) mode. Ion transitions monitored for quantitation were m/z 268.2 → 74.1 for MET, m/z 409.1 → 238.0 for AML, m/z 341.2 → 91.0 for CAN and m/z 296.0 → 205.1 for HCT. For all analytes, inter- and intra-day precision (CV, %) varied between 1.7 and 14.0 and inter- and intra-day accuracy values ranged from -2.5 to 7.1%. The lower limits of detection and quantification were: 0.08 and 0.23; 0.05 and 0.15; 2.82 and 8.54; and 0.02 and 0.05 µg/l for MET, AML, CAN and HCT, respectively. Results of stability experiments were within the required range of +/- 15%. CONCLUSIONS: Although the level of recommendation of TDM of antihypertensive drugs in patients with refractory hypertension is not yet established, the present LC-MS/MS-method can serve as an effective tool for detection of PK-alterations/nonadherence and may help to monitor antihypertensive pharmacotherapy.