Adrenocortical hypertension

Primary aldosteronism, congenital adrenal hyperplasia, Cushing’s syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also, new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing’s syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.     

Diagnosis and treatment of low-renin hypertension

Plasma renin levels can be used to classify hypertension. A significant proportion of hypertensive individuals display a low-renin profile and thus low-renin hypertension (LRH) requires appropriate diagnosis and treatment. LRH includes essential, secondary and genetic forms, the most common of which are low-renin essential hypertension and primary aldosteronism. Several studies have investigated the relationship between PRA status and clinical response to different antihypertensive therapies. The present review will discuss the differential diagnosis of LRH subtypes and the most appropriate treatment options based on the pathophysiological background of this condition.     

Pulmonale Hypertonie

Pulmonary hypertension (PH) is a devastating disease that, if untreated, is characterized by a poor prognosis. According to the current classification (Venice, 2003), pulmonary arterial hypertension (PAH) is distinguished from other forms of PH. Recent advances in drug therapy have led to a dramatic improvement in medical care, particularly in patients with PAH. Hence, early establishment of the diagnosis and a precise classification appear increasingly important. This review provides an overview on the definition, classification, pathophysiology, and clinical presentation of various forms of PH. Furthermore, it summarizes the recommended diagnostic work-up and current treatment options, particularly for PAH, with special emphasis on prostanoids, endothelin receptor antagonists (ERAs), and phosphopdiesterase type 5 (PDE5) inhibitors such as sildenafil. Finally, novel developments are discussed which currently represent an exciting field of basic and clinical research.     

Aldosterone Excess and Resistant Hypertension: Investigation and Treatment

Among patients with resistant hypertension, primary aldosteronism (PA) is worth detecting as it appears to be particularly common in this cohort. It is associated with excessive cardiovascular morbidity in relation to the degree of hypertension and reduced quality of life, both of which can be abrogated with specific surgical or medical treatment. Knowledge concerning factors (including medications) which can influence the results of screening by aldosterone/renin ratio (ARR) testing is expanding, and is important to appreciate, particularly in patients with resistant hypertension, in whom the need for multiple medications can render interpretation challenging. Advances in approaches to confirmatory testing, subtype differentiation and assay methodology are helping to improve feasibility and reliability of the diagnostic workup for PA and new treatment approaches are emerging. Major developments in understanding the genetic bases for PA hold promise towards further improvements and options in diagnosis and therapy.     

The adult patient with eisenmenger syndrome: a medical update after dana point part I: epidemiology, clinical aspects and diagnostic options

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on epidemiology, clinical aspects and specific diagnostic options.     

Diagnostik der pulmonalen Hypertonie

Chronic pulmonary hypertension (PH) is defined as a permanently increased mean pulmonary artery pressure ≥25 mmHg as assessed by right heart catheterisation and is associated with a poor prognosis without therapy. Depending on pathological, pathophysiological and therapeutic characteristics, clinical conditions with PH are classified into five groups. An exact diagnostic classification is necessary for application of the current treatment options for the different forms of PH. The first symptoms of PH are non-specific; therefore an early diagnosis is difficult. The current guidelines propose a new diagnostic algorithm to improve the precise diagnostic workup. In any case of suspected PH transthoracic echocardiography should be performed. If signs of PH are found, underlying left heart disease and lung diseases need to be searched for. In the case of exclusion or presence of “out of proportion PH”, which is not explained by underlying disease, a systematic evaluation is needed to clarify the specific aetiology and clinical group of PH and to quantify the functional and haemodynamic impairment.     

Pulmonary arterial hypertension (PAH) in connective tissue diseases

Pulmonary arterial hypertension (PAH) is characterized by progressive obliteration of the small pulmonary vascular bed as a result of vascular proliferation and remodelling of the vessel wall leading to permanently increased pulmonary vascular resistance and elevated pulmonary artery pressures, which result in right heart failure and premature death. Pathologic processes behind the complex vascular changes associated with PAH include vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and inflammation. Besides idiopathic PAH, it can also occur in association with portal hypertension, HIV infection, congenital cardiac left-to-right shunts and connective tissue diseases (CTD). Unfortunately, despite recent major improvements in PAH treatment, no current therapy can yet cure this devastating condition. This review will briefly highlight epidemiology, pathogenesis, and diagnostic and treatment options known so far for PAH occurring in connection with CTD.     

Genetic Factors in Hypertension - What is Known and What Does It Mean?

The cause of primary hypertension is unknown but the normal distribution of blood pressure in the population, of which hypertension represents the upper tail, suggests a multifactorial aetiology. Approximately 30%-60% of the blood pressure variation in the population is accounted for by genetic factors whereas environmental exposure explain the remaining part [1, 2]. Primary hypertension is likely to be the result of the net effect of various environmental factors and number of common variants in different genes, each of which will have a moderate effect on blood pressure [3]. Thus hypertension susceptibility genes will occur also in the normotensive segment of the population, although less frequently than in hypertensive patients. The exact genetic defects of a number of rare salt sensitive monogenic forms of hypertension have been described [4-6]. The causative mutations all lead to increased reabsorption of sodium in the renal tubules. These discoveries have highlighted the clinical relevance of searching for hypertension genes as they have allowed for early diagnosis, prevention with salt restriction and specific and effective pharmacological treatment of these monogenic forms of hypertension. The genetic background of primary hypertension is more complex and considerably harder to dissect as the number of genes and environmental factors involved are greater, resulting in a "non-Mendelian" inheritance pattern. However, thanks to the recent enormous development of molecular genetics [7], genetic statistics [8, 9] as well as of advances in clinical hypertension research, identification of primary hypertension susceptibility genes now seems feasible. This article reviews the strategies that can be used for hypertension susceptibility gene identification and gives an overview of the as yet most important findings in the field of genetics of hypertension. Finally, views on what we can expect from this research field in the future and what impact it will have on clinical medicine are put forward.     

Clinical insights into the diagnosis and management of atherosclerotic renal artery disease

Atherosclerotic renovascular disease (ARVD) is an increasingly common contributor to hypertension and renal failure. However, not all patients with an identified obstructive atherosclerotic renal artery stenosis will have clinical improvement, even after successful percutaneous intervention. As such, there remains extensive controversy regarding optimal diagnostic and treatment strategies. Part of this controversy is the result of a paucity of well-designed prospective, randomized clinical trials, but the complex nature of the disorder and the heterogeneity of patients presenting with possible ARVD make simple diagnostic and treatment paradigms difficult to develop. This narrative review describes the latest observations concerning the prevalence, pathogenesis, natural history, diagnostic studies, and treatment options for suspected ARVD. Hopefully, this knowledge will improve the ability of clinicians to weigh risks and benefits and determine the best strategy in individual patients.     

Overview and implications of obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a leading public health problem both in the developed and developing nations. However, awareness regarding diagnostic options, management and consequences of untreated OSA remains inadequate. In developing nations, the resources for adequate sleep medicine facilities are scarce. Therefore, there is a need for low cost, simple and accurate diagnostic and therapeutic modalities exists. Untreated OSA leads to excessive daytime sleepiness, diminished performance and an overall poor quality of life. The role of OSA in promoting insulin resistance, atherosclerosis, hypertension and a procoagulant state has now been established. Newer insights into the biochemical and genetic mediators of OSA have raised hopes regarding the development of a "cure". However, as of now, continuous positive airway pressure (CPAP) therapy remains the first-line treatment. Though its use improves the quality of life as well as metabolic derangements observed in OSA, patients' acceptance remains low. Its high cost and long-term use are also cumbersome. Newer modes of delivering CPAP, oral appliances and upper airway surgery are the other options available. It is hoped that their appropriate use to increase patients' compliance may improve the quality of life as well as provide a survival benefit.     

Diagnosis and management of renovascular hypertension

Renovascular hypertension caused by renal artery stenosis accounts for a small portion of overall hypertension but remains important as the most common potentially curable form of high blood pressure. Diagnosis depends on developing an index of suspicion for renovascular hypertension based on the history and physical exam, as well as judicious use of noninvasive and invasive testing. Determining which noninvasive diagnostic test to use remains a persistent dilemma. Treatment options include renal artery angioplasty, arterial stenting, surgery, and medical therapy. The goals of therapy are reduction of blood pressure and protection of renal function. This review discusses the pathophysiology and epidemiology of renovascular hypertension, various noninvasive tests used in diagnosis, and results offered by different treatment modalities. A diagnostic and therapeutic algorithm is offered based on a review of the literature and the experience at our institution.     

Genetic aspects of endocrine hypertensive disorders

Arterial hypertension is associated with high morbidity and mortality indices and constitutes a major health problem worldwide, specially due to its high prevalence and low rate of control with the standard treatment. This problem can be explained, at least in part, because we still use empiric measures when choosing treatment options, instead of a rational approach for each case. The determinants of the hypertension remain unknown in the majority of patients and is designated as essential or primary hypertension. Hypertension is a model of complex disease in which several genes may be affected and influenced by a variety of environmental interactions, such as diet, salt and obesity, among others. The use of molecular biology strategies is offering new opportunities for the understanding of complex biological phenomena, like hypertension. However, only in a minority of cases, arterial hypertension occurs by individual specific mutations, called mendelian forms of hypertension, involving distal nefron transporter gene products. These syndromes are of particular interest since they highlight the importance of cell pathways that can be affected in the more common forms of hypertension.     

The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on the medical treatment and corresponding study results.     

Sklerodermie

Scleroderma (synonyms: systemic sclerosis, systemic scleroderma) is a systemic disease which affects the skin as well as internal organs such as the lungs, gastrointestinal tract, kidneys, and the heart. Pathogenetically a distinction should be made between uncontrolled formation of extracellular matrix proteins (fibrosis) and vasculopathy. In addition to organ fibrosis, this leads to a clinical picture of vascular manifestations. These include fingertip ulcers, pulmonary arterial hypertension, and acute renal crisis. Localized forms of scleroderma, such as morphea, which do not involve organ complications, should be differentiated from systemic sclerosis. Due to its clinical heterogeneity and high rate of morbidity and mortality, systemic sclerosis poses an enormous diagnostic and therapeutic challenge in everyday clinical practice. This review article summarizes the current status of classification and epidemiology, pathogenesis, and the most important clinical manifestations such as interstitial fibrosis, pulmonary arterial hypertension, acute renal crisis, and peripheral vasculopathy and provides an overview of current and future treatment options.     

Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea

This article is aimed at addressing the current state of the art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnea (OSA) in cardiovascular (particularly hypertensive) patients, as well as for the management of cardiovascular diseases (particularly arterial hypertension) in OSA patients. The present document is the result of the work done by a panel of experts participating in the European Union COST (COoperation in Scientific and Technological research) ACTION B26 on OSA, with the endorsement of the European Respiratory Society (ERS) and the European Society of Hypertension (ESH). These recommendations are particularly aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are at the same time aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.     

Post–Gastric Bypass Hypoglycemia

Obesity is a major public health problem worldwide. Obesity-related illnesses, such as coronary heart disease, type 2 diabetes, hypertension, dyslipidemia, stroke, sleep apnea, and several forms of cancer (endometrial, breast, and colon), contribute to a significant number of deaths in the USA. Bariatric surgery, including the Roux-en-Y gastric bypass (RYGB) procedure, has demonstrated significant improvements in obesity and obesity-related co-morbidities and is becoming more popular as the number of obese individuals rises. Despite the reported benefits of bariatric surgery, there are potential complications that physicians need to be aware of as the number of patients undergoing these procedures continues to increase. One challenging and potentially life-threatening complication that to date is not well understood is post-RYGB surgery hypoglycemia (PGBH). In this review, we will present the definition, historical perspective, diagnostic approach, currently available treatment options, and anecdotal assessment and treatment algorithm for this disorder.     

Dilated Cardiomyopathies as a Cause of Congestive Heart Failure

DEFINITION AND CLASSIFICATION: Cardiomyopathies are disorders affecting the heart muscle that frequently result in congestive heart failure. Five major forms are recognized: dilated, hypertrophic, restrictive, right ventricular, and nonclassifiable cardiomyopathies with distinct hemodynamic properties. Furthermore, the new WHO/WHF definition also comprises inflammatory cardiomyopathy, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy is defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm2), the term viral cardiomyopathy or viral persistence in dilated cardiomyopathy should be applied. DIAGNOSIS AND TREATMENT: In recent years, there have been breakthroughs in understanding the molecular and genetic mechanisms involved in this group of conditions, enabling improvement of diagnostic strategies and introduction of new therapies. Ongoing evaluation of antiviral, immunoglobulin, and immunosuppressive therapies including the European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID), removal of antibodies by immunoadsorption, anticytokine and gene therapy, as well as the mechanical support devices may provide new treatment options.     

Around-the-clock Ambulatory Blood Pressure Monitoring is Required to Properly Diagnose Resistant Hypertension and Assess Associated Vascular Risk

Obesity is prevalent worldwide and associated with co-morbidities that result in increased cardiovascular risk. Hypertension is the most prevalent obesity comorbidity associated with increased cardiovascular risk. Obesity hypertension is a distinct subtype of essential hypertension. While endogenous Cushing’s syndrome is an uncommon cause of both obesity and hypertension, the recent recognition of other hypercortisolemic states has raised the profile of hypercortisolism as an important contributor in obesity hypertension. The high prevalence of exogenous, iatrogenic, pseudo, and subclinical Cushing’s syndromes makes hypercortisolism an important diagnostic consideration in the evaluation and management of patients with obesity hypertension who are resistant to conventional management. Available data suggest that the renin-angiotensin-aldosterone system modulating antihypertensives have the best efficacy in hypercortisolism-mediated obesity hypertension. Strategies aimed at reducing cortisol production and action also have utility. This review provides a comprehensive overview of the epidemiology, etiopathogenesis and management options available for glucocorticoid-mediated obesity hypertension.     

Pulmonary complications of hemoglobinopathies

Hemoglobinopathies are diseases caused by genetic mutations that result in abnormal, dysfunctional hemoglobin molecules or lower levels of normal hemoglobin molecules. The most common hemoglobinopathies are sickle cell disease (SCD) and the thalassemias. In SCD, an abnormal hemoglobin alters the erythrocyte, causing a chronic hemolytic anemia, which can lead to pulmonary parenchymal damage and impaired vascular function. Pulmonary complications of SCD include the acute chest syndrome (ACS), reactive airways disease, pulmonary hypertension (PH), and pulmonary fibrosis. Episodes of ACS and the development of PH both increase the risk of death in patients with SCD. Both α and β thalassemia are characterized by impaired production of hemoglobin subunits, and severity of disease varies widely. Although screening studies suggest that PH is a common complication for patients with thalassemia, its impact on survival is unknown. Understanding the pathogenesis, diagnostic options, and prevention and treatment strategies for such complications is critical for clinicians who care for these patients. In this review, we discuss the mechanisms and clinical presentation of pulmonary complications associated with hemoglobinopathies, with a focus on recent advances in pathogenesis and treatment.     

The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part III: Specific Management and Surgical Aspects

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on specific management and surgical aspects.