Narrative review: the holy grail: update on pharmacotherapy for heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is the presence of clinical signs and/or symptoms of heart failure with a left ventricular ejection fraction (LVEF) ≥50%. Risk factors associated with this disease include hypertension, hyperlipidemia, atrial fibrillation (AF), obesity, diabetes and coronary artery disease (CAD). Despite the multiple risk factors identified for this condition, treatment and management remain challenging and a subject of ongoing research. Since a treatment approach that alters the natural course or lowers mortality for this disease has not been found, treating co-morbidities and symptom management is essential. From the comorbidities, hypertension is identified as the main risk factor for disease development. Thus, after congestive symptom control with diuretics, blood pressure (BP) management is considered one of the most important preventive measures and also a target for treatment. Amongst antihypertensives, angiotensin receptor blockers (ARBs) and aldosterone antagonists are the therapeutic agents used that have a role in reducing hospitalizations. Implantable monitoring devices have also been shown to reduce hospitalizations in comparison to standard heart failure therapies by allowing to tailor diuretic therapy based on ongoing hemodynamic data. In this manuscript we discuss pharmacologic strategies for HFpEF patients by risk factors, including those with and without a potential role.

Diuretic Resistance in Heart Failure.

Decompensated heart failure accounts for approximately 1 million hospitalizations in the United States annually, and this number is expected to increase significantly in the near future. Diuretics provide the initial management in most patients with fluid overload. However, the development of diuretic resistance remains a significant challenge in the treatment of heart failure. Due to the lack of a standard definition, the prevalence of this phenomenon remains difficult to determine, with some estimates suggesting that 25-30% of patients with heart failure have diuretic resistance. Certain characteristics, including low systolic blood pressures, renal impairment, and atherosclerotic disease, help predict the development of diuretic resistance. The underlying pathophysiology is likely multifactorial, with pharmacokinetic alterations, hormonal dysregulation, and the cardiorenal syndrome having significant roles. The therapeutic approach to this common problem typically involves increases in the diuretic dose and/or frequency, sequential nephron blockade, and mechanical fluid movement removal with ultrafiltration or peritoneal dialysis. Paracentesis is potentially useful in patients with intra-abdominal hypertension.

Swimming-induced pulmonary edema.

Swimming-induced pulmonary edema occurs when fluid accumulates in the lungs in the absence of water aspiration during swimming and produces acute shortness of breath and a cough with blood-tinged sputum. We report a case of a 58-year-old female athlete presenting with acute dyspnea during the swimming portion of a half-triathlon competition. She had complete resolution within 24 h of presentation.

A lymphoproliferative pericardial mass.

Castleman disease (CD) is a rare lymphoproliferative disorder with variable presentation and prognosis. Most CD cases are unicentric and correspond to the hyaline-vascular variant, a histopathological classification associated with better outcomes, which commonly presents as an enhancing hypervascular mediastinal mass. CD is often asymptomatic and surgically resectable. Nonetheless, surgical resection can be difficult when the lymphoid mass is causing compression of vital structures. We discuss a rare case of hyaline-vascular unicentric CD presenting as an incidental pericardial mass.

Cardiogenic Pulmonary Edema.

The initial events in cardiogenic pulmonary edema involve hemodynamic pulmonary congestion with high capillary pressures. This causes increased fluid transfer out of capillaries into the interstitium and alveolar spaces. High capillary pressures can also cause barrier disruption which increases permeability and fluid transfer into the interstitium and alveoli. Fluid in alveoli alters surfactant function and increases surface tension. This can lead to more edema formation and to atelectasis with impaired gas exchange. Patients with barrier disruption have increased levels of surfactant protein B in the circulation, and these levels often remain high after the initial clinical improvement. Routine clinical assessment may not identify patients with increased extravascular fluid in the lungs; pulmonary ultrasound can easily detect pulmonary edema in patients with acute decompensation and in patients at risk for decompensation. Studies using serial pulmonary ultrasound could help characterize patients with cardiogenic pulmonary edema and help identify subgroups who need alternative management. The conventional management of cardiogenic pulmonary edema usually involves diuresis, afterload reduction and in some cases noninvasive ventilation to reduce the work of breathing and improve oxygenation. Patients with persistent symptoms, abnormal chest x-rays and diuretic resistance might benefit from alternative approaches to management. These could include beta agonists and pentoxifylline which warrant more study in patients with cardiogenic pulmonary edema.

Lung morphology and surfactant function in cardiogenic pulmonary edema: a narrative review.

The conventional analysis of acute cardiogenic pulmonary edema involves the development of high pulmonary capillary pressures resulting in hydrostatic gradients for fluid flux out of capillaries into the interstitial space and alveolar spaces. However, some patients respond poorly to diuretic management. The PubMed database was searched to identify experimental studies on pulmonary edema in animals, experimental studies on surfactant function, including patients with pulmonary edema, and clinical studies reporting barrier dysfunction and/or injury in patients with acute pulmonary edema. Studies with animal models demonstrate that high capillary pressures can cause barrier disruption in alveolar capillary units which increases permeability and the transfer of fluid and protein into lung parenchyma. Fluid in alveolar spaces alters surfactant function which increases fluid flux out of capillaries into the lung parenchyma secondary to larger transcapillary hydrostatic gradients. Patients with acute cardiogenic pulmonary edema have increased levels of surfactant protein B in their plasma which reflect barrier disruption and increased levels of tumor necrosis factor alpha which reflect acute tissue injury. Increased surfactant protein B plasma levels are associated with abnormal gas exchange in patients with chronic heart failure. Patients with exercise-induced left ventricular dysfunction have increased levels of surfactant protein B after short periods of exercise. Pathology studies in patients with chronic heart failure have found increased connective tissue in alveolar capillary units and increased numbers of type II alveolar cells, and these changes represent an adaptive response in these patients. Clinicians need to consider the possibility of barrier dysfunction and disruption in patients with both acute and chronic pulmonary edema and understand that diuresis may have a limited effect on symptoms in some patients.

Oligomerization studies show that the kinase domain of the tomato pollen receptor kinase LePRK2 is necessary for interaction with LePRK1.

LePRK1 and LePRK2 are two pollen-specific receptor-like kinases from Solanum lycopersicum that are involved in signaling during pollen-pistil communication. Previously, we showed that both proteins interact in pollen and when expressed in yeast. We also showed that pollen tube length was regulated by phosphorylation of specific residues in the juxtamembrane domain of LePRK2. To determine the domains responsible for the interaction between LePRK1 and LePRK2, we constructed a series of deletions, expressed them in yeast and determined their association by co-immunoprecipitation assays. We show that deletions containing extracellular domains of LePRK1 and LePRK2 were glycosylated in yeast and were sufficient for interaction with the corresponding full-length receptor. The juxtamembrane domain of LePRK1 was sufficient for its interaction with LePRK2, whereas LePRK2 required its kinase domain for interaction with LePRK1. These findings suggest a role for the juxtamembrane domain of LePRK2 in mediating intracellular dimerization and thus receptor kinase phosphorylation.

Doença de Milroy-Meige-Nonne / Milroy-Meige-Nonne's disease

A doença de Milroy-Meige-Nonne é uma forma primária de edema linfático, geralmente localizada nos membros inferiores e bilateral. A moléstia é causada pela drenagem linfática inadequada, devido ao desenvolvimento anormal dos vasos linfáticos. Trata-se de condiçäo hereditária com transmissäo autossômica dominante. O caso apresentado é de linfedema congênito localizado no membro inferior esquerdo. Seis outros familiares da paciente em estudo também apresentaram linfedema congênito