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Background: The objective of this study was to test whether baseline echocardiography in newly detected hypertension improves left ventricular mass index and blood pressure control. This is a randomized trial with primary care patients. Methods: After routine clinical work-up 177 consecutive patients with newly detected hypertension were randomized according to result of their echocardiogram (echo group and control group). Treating physicians were encouraged to prescribe angiotensin II receptor antagonist therapy for patients with evidence of hypertensive target organ damage. Mean blood pressure (BP) and echocardiographic left ventricular mass index were measured at baseline and after 6 months of therapy in both groups. Results: More patients with hypertensive target organ damage were identified in the echo group as compared to the control group (58 of 91 [64%] v 42 of 86 [49%] patients (difference 15%, 95% CI 1%–29%). In the echo group, 41 patients (45%) received angiotensin II receptor antagonist therapy as compared to 27 patients (31%) in the control group (difference 14%, 95% CI 0–28%). After 6 months, there were no differences in mean left ventricular mass index, mean diastolic 24-h ambulatory BP monitoring, or mean systolic and diastolic office BP between the two groups. Conclusions: In patients with newly detected hypertension, baseline echocardiography detects more patients with hypertensive target organ damage, but does not lead to a reduction in left ventricular mass index or improved BP control after 6 months of therapy. [Copyright &y& Elsevier]

Abstract: Background: Abnormalities of intracellular calcium handling are widely recognized as a common hallmark of heart failure in animal models and humans. Modifying the interaction of phospholamban (PLB) with the sarcoplasmic reticulum ATPase (SERCA) by PLB mutants improves cardiac function but may also lead to heart failure. In this study we describe the in vivo effects of a new approach to modify the PLB–SERCA interaction using a recombinant, intracellularly expressed chicken-antibody derived protein (PLADP) targeting the cytoplasmic domain of PLB in the cardiomyopathic BIO 14.6 hamster. Methods and results: In vivo gene transfer was performed in 12–14-week-old BIO 14.6 cardiomyopathic hamsters using intracoronary delivery of adenovirus containing the PLADP or the β-galactosidase (LacZ) gene (8×109 PFU per animal). A third group was injected with saline (Sham). Echocardiography was performed before and, together with hemodynamic measurements, repeated 4–5 days after gene transfer. Indo-1 calcium transients and myocyte contractility were measured in isolated cardiomyocytes from the BIO 14.6 hamster transfected with the PLADP. Gene expression (LacZ) was found in 54±15% of cells throughout the heart without any signs of myocardial inflammation. Echocardiographic and hemodynamic indices of left ventricular function were significantly increased after gene transfer with the PLADP, compared to controls. Measurements of myocyte contractility and calcium transients in isolated cardiac myocytes from BIO 14.6 hamsters revealed improved intracellular calcium handling and contractility. Conclusion: In vivo adenoviral gene transfer with the PLADP resulted in short-term intracellular expression of a PLADP, improving LV function and enhancing myocardial contractility in the failing cardiomyopathic hamster heart. The PLADP enhanced contractility and cardiac function by improving intracellular calcium handling. Expression of antibody-derived protein represents a new approach to modify protein–protein interactions at the cellular level. [Copyright &y& Elsevier]

Background: The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations. There are numerous reasons for the lack of disease control in asthma and COPD patients. It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient. This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence.Methods: For this cross-sectional analysis, 165 asthma and COPD patients were analyzed. Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type. QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT). Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).Results: Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02). Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02). While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (P = .04).Conclusions: Correct inhalation of prescribed medication is associated with improved health status and lung function. These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients' inhalation technique.Trial Registration: ClinicalTrials.gov: NCT0238672 , Registered 14 February 2014. [ABSTRACT FROM AUTHOR]

Background and Objective: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown., Method: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD., Results: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD., Conclusions: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Scientific advances and innovative targeted drugs, especially biologics, have revolutionised the treatment of many diseases. In oncology in particular, previously acute or lethal conditions have come to be considered chronic as new treatments have led to longer life expectancies and a lower rate of years lived with disability. These advances, however, come with rising costs in a resource-constrained environment. To achieve cost containment, reimbursement for in-vitro diagnostics (IVDs) is increasingly coming under pressure because they are perceived as a cost factor rather than as a tool to reduce expenditure in the long term. In this conceptual paper, we propose four possible interventions from an industry perspective that may contribute to increase effectiveness of IVD use to counteract increasing healthcare expenditures. These are: (1) fostering prevention, screening, early diagnosis and therapy; promoting (2) comprehensive and (3) stratified disease management; and (4) using targeted treatment alongside companion diagnostics. We conclude that the implementation of policies that promote a fee-for-outcome model rather than fee-for-service reimbursement can support sustainable healthcare.

Due to the high prevalence of cardiovascular diseases and the corresponding prescription of cardiac drugs, side effects and interactions may occur in a substantial number of patients. They can be explained by either pharmacokinetic or pharmaco-dynamic drug interactions which may be desired, but may also be life-threatening. Despite the fact that the novel oral anticoagulants are well tolerated, several factors restricting the use of these drugs, such as renal failure, have to be considered. The use of antihypertensive drugs may be limited by concomitant use of drugs that either induce of inhibit enzymatic metabolism, respectively inhibit renal drug, electrolyte, and/or water excretion. In this respect, the interaction between beta-blockers, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics with non-steroidal antiinflammatory drugs is especially important. Muscle disorders are frequent side effects in patients undergoing statin therapy and affect up to 5% of patients. They may manifest as mild myalgia, but also as life-threatening rhabdomyolysis.

European and North-American guidelines for the diagnosis and therapy of arterial hypertension refer to hypertensive crisis as an acute and critical increase of blood pressure>180/120 mmHg. Presence of acute hypertensive target organ damage, such as stroke, myocardial infarction or heart failure, in this situation defines a “hypertensive emergency”. In these patients, immediate lowering of blood pressure (about 25% within one to two hours) in an intensive care setting is mandatory to prevent further progression of target organ damage. In contrast to hypertensive emergencies, hypertensive urgencies are characterized by an acute and critical increase in blood pressure without signs or symptoms of acute hypertensive target organ damage. In these patients, blood pressure should be lowered within 24 to 48 hours in order to avoid hypertensive target organ damage. In general, hospitalization is not required, and oral antihypertensive therapy usually is sufficient. However, further and continuing outpatient care has to be ensured.

To improve the prevention of cardiovascular complications and events in hypertensive patients, it is of major importance to estimate the patient's individual risk for cardiovascular events. Antihypertensive treatment should not only be based on blood pressure values anymore, but also on the patient's comorbidities and risk profile. Risk stratification takes into account cardiovascular risk factors, diabetes, asymptomatic organ damage and established cardiovascular or renal disease. The most important markers for asymptomatic organ damage which should be searched for are microalbuminuria and LVH. Current guidelines emphasize the importance of the adaption and selection of treatment according to asymptomatic and established organ damage and provide assistance for treatment decisions. They focus also on the different non-pharmacological therapy options and lifestyle modifications. The goal of this article is to summarize the most important innovations and to point out the importance of simple tools for the implementation of cardiovascular risk stratification in hypertensive patients.

Arterial hypertension remains the most important risk factor for cardiovascular and renal diseases. In view of an increasing prevalence with older age and an increasingly aging population, the treatment of elderly patients with arterial hypertension will become increasingly important in daily practice. Arterial hypertension in the elderly differs in many aspects from arterial hypertension in younger patients. For example, isolated systolic hypertension is the predominant form of arterial hypertension in the elderly. In comparison to younger patients, treatment of hypertension in the elderly is less well investigated. However, available data suggest that lowering of blood pressure in the elderly and very elderly reduces the risk of heart failure, stroke, and even mortality. The best evidence for the treatment of hypertension in the elderly exists for diuretics and calcium antagonists. However, the primary choice of antihypertensive therapy should be guided by the presence of existing cardiovascular and/or renal comorbidities.

Therapy-resistant hypertension is a frequent finding in clinical practice. It is associated with a significantly increased risk for cardiovascular and renal events. Causes include but are not limited to erroneous blood pressure measurements, compliance issues, blood pressure increasing co-medication, and secondary hypertension. During the last years, several medical and interventional therapeutic approaches have been described and introduced into clinical practice. The goal of this paper is to summarize the clinically relevant diagnostic and therapeutic aspects related to therapy-resistant hypertension and to give an overview on the rational approach to this clinical problem.

The recommendations of international scientific societies for the treatment of hypertension in the geriatric population are different. Lack of outcome trials, non-standardised terminology as well as differing levels of evidence contribute to the inconsistencies in the guidelines. This review article compares six international guidelines (ESH-ESC 2007/2009, SHG 2009, DHL 2008, CHEP 2010, NICE 2011 and JNC7 2003) as well as the consensus document of the ACCF/AHA 2011 in terms of their recommendations of drug classes, target blood pressure values and the use of combination therapy. Generally, antihypertensive therapy appears to be clinically beneficial in geriatric patients. Target blood pressure values of <140-150/90 mm Hg and <140/90 mm Hg can be used as a general guideline for octogenarians (80-89 yrs) and septuagenarians (70-79 yrs) respectively. While angiotensin-II converting enzyme inhibitors and diuretics appear to be advantageous in treating combined systolic-diastolic hypertension, calcium-channel blockers and diuretics are to be recommended in the management of isolated systolic hypertension. Combination therapy often increases the efficacy of the treatment as well as patient medication adherence. Furthermore, by making the most of drug combination synergy, lower doses may be used resulting in fewer side-effects.

In coronary artery disease, cardiovascular risk factors are the main targets for primary and secondary prevention. Statins prevent cardiovascular events in patients at risk. However, despite the proven efficacy and safety of statins, relevant side effects exist and should be considered when treating patients.

Arterial hypertension continues to represent the leading cause of morbidity and mortality world-wide. Diagnosis and therapy of arterial hypertension require adequate blood pressure measurements. Blood pressure is affected by constitutional and environmental factors as well as the measurement procedure itself, inducing substantial uncertainty with regard to adequate diagnosis and control of arterial hypertension. Therefore, current guidelines recommend that the diagnosis of arterial hypertension should not be solely based on conventional blood pressure measurements in the physician's office or in the hospital, but also on out-of-office ambulatory or home blood pressure measurements using clinically validated semi-automated or automated blood pressure measurement devices. Despite the enormous progress in the field of arterial hypertension, many aspects of blood pressure measurement require further intensive investigation, for example blood pressure measurement in special populations and distinct clinical situations, as well as the applicability and validation of novel measurement approaches and devices. This article provides an overview of current methods and trends in the field of non-invasive blood pressure measurement, an update on current clinical guidelines and an overview of blood pressure measurement in special populations.

Diastolic heart failure, also termed as heart failure with normal or preserved ejection fraction has a high prevalence and mortality world wide. The clinical manifestation comprises typical symptoms and signs of heart failure along with normal or discretely reduced left ventricular ejection fraction. Though the etiology of diastolic heart failure is incompletely understood, functional and structural abnormalities of cardiomyocytes, the extracellular matrix, and the peripheral vasculature are assumed to contribute to the etiology of diastolic heart failure. The diagnosis requires typical symptoms and signs of heart failure, evidence of elevated natriuretic peptides and an impaired diastolic ventricular function, meanwhile left ventricular systolic function is normal or just slightly impaired. Catheter and MRI exams help to ensure the diagnosis. So far, no therapy has convincingly demonstrated a reduction of morbiditiy and mortality. Therefore, current guidelines emphasize the importance of an adequate treatment of risk factors and myocardial ischemia.

Background: In daily routine, physicians use history, physical examination and technology-based information such as laboratory tests and imaging studies to diagnose the patients' disease. We determined the diagnostic value of lung auscultation in patients admitted to the Medical emergency room with chest symptoms., Methods: Two-hundred-and forty-three consecutive patients (137 males), mean age 59.2 years were included. Internal Medicine registrars had to make a presumptive diagnosis, 1) after having taken the history and 2) after having auscultated the lungs. Thereafter, routine diagnostic procedures were performed. The estimated diagnosis was compared with the final diagnosis based on the written report to the Family Practitioner., Results: Two-hundred-eighty-seven diagnoses were made. Eighteen percent of patients suffered from left heart failure, 13% from unexplained chest pain, 10.5% from chest wall pain, and 10.5% from pneumonia. Forty-one percent of the diagnoses were already correct when based only on the patient's history. Lung auscultation improved the diagnostic yield only in 1% and worsened it in another 3%. By multiple logistic regression, normal lung auscultation (OR 0.12 [95CI% 0.053-0.29]) was the independent predictor for not having a lung or heart disease. However, elevation of B-type natiuretic peptide (BNP) (OR 1.16 per 100 pg/ml (95CI% 1.004-1.35), wheezing (OR 0.023 [0.002-0.33]) and pCO2 (OR 0.25 (0.10-0.621) were independent predictors for having a heart disease, whereas wheezing (OR 7.41 [3.26-16.83]) and CRP (OR 1.008 per 10 units [1.003-1.014]) were risk factors for having a lung disease., Conclusion: In contrast to history taking, abnormal lung auscultation does not appear to contribute considerably to the final diagnosis in patients presenting with chest symptoms in an emergency room setting. However, normal lung auscultation is a valuable predictor for not having a lung or heart disease, whereas wheezing is a predictor for having a lung disease and not having a heart disease.