Respiratory stability time and heart failure severity.

BNP in Overweight and Obese Patients With Heart Failure: An Analysis Based on the BNP-LV Diastolic Wall Stress Relationship

This review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level. We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals. These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively. One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail. Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the high-altitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension. ### Circulation The major effects of acute hypoxia on the heart and lung are shown in Figure 1. Hypoxia directly affects the vascular tone of the pulmonary and systemic resistance vessels and increases ventilation and sympathetic activity via stimulation of the peripheral chemoreceptors.1 Interactions occur between the direct effects of hypoxia on blood vessels and the chemoreceptor-mediated responses in the systemic and pulmonary circulation. Figure 1. Effects of hypoxia on systemic and pulmonary circulation. Unraveling the underlying mechanisms of the hypoxic vasodilatation of systemic arterioles is an active area of research. Several mechanisms appear to regulate local oxygen delivery according to the needs of the tissues2,3; for instance, the release of ATP from red blood cells and the generation of NO by various ways appear to regulate local oxygen delivery according to the needs …

Recently, fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone, has been linked to the pathophysiology of heart failure (HF), thus encouraging us to examine which hemodynamic abnormalities of HF are linked to either serum FGF23 or plasma B-type natriuretic peptide (BNP) levels. We measured both the serum FGF23 and plasma BNP levels in 154 consecutive prospectively enrolled hospitalized HF patients, with an estimated glomerular filtration rate >40 ml min-1 1.73 m-2, who underwent heart catheterizations and an echocardiogram. The serum FGF23 levels correlated with the diameter of the inferior vena cava and its respiratory changes, whereas the plasma BNP levels did not. Both the plasma BNP and serum FGF23 levels were moderately correlated with the mean pulmonary artery (PA) pressure and pulmonary capillary wedge (PCW) pressure. Interestingly, in patients with an above-median right-atrial (RA) pressure (4 mm Hg), FGF23 levels were correlated with both PA and PCW pressures, but the levels were not correlated in patients with a below-median RA pressure. In contrast, the plasma BNP levels were correlated with both PA and PCW pressures. Finally, serum FGF23 levels, compared with the plasma BNP levels, were more strongly associated with the clinical outcomes in patients with above-median RA pressure. These findings suggested that serum FGF23 levels are predominantly correlated with clinical outcomes, may serve as a biomarker for HF in patients with higher RA pressure, may provide beneficial information for patients with right-sided HF and may represent different clinical information than that provided only by plasma BNP levels.

We aimed to study the relationships of loop diuretic dose with renal function and clinical outcomes in patients with chronic heart failure (HF). Loop diuretic dose at baseline was recorded in patients included in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). The relationship to change in estimated glomerular filtration rate (eGFR) over time and to the first occurrence of the composite outcome of cardiovascular (CV) death or hospitalization owing to HF was examined in propensity score matched cohorts. Of the 5011 patients, 2550, 745, and 449 were receiving >80 mg (high), 41-80 mg (medium) and ≤40 mg (low) of loop diuretics in furosemide equivalent daily dosages, respectively, which were used to assemble 229, 385, and 1045 pairs of propensity-matched high, medium, and low dose cohorts. Compared with matched no loop diuretic groups, eGFR declined 0.3 ± 0.2, 0.3 ± 0.3 and 1.2 ± 0.5 mL/min/1.73 m(2) /year in the low-, medium-, and high-dose groups, respectively. Compared with matched no loop diuretic groups, hazard ratios (HR) (95% confidence intervals) for outcome associated with low-, medium- and high-dose groups were 1.71 (1.41-2.06), 1.99 (1.50-2.64), and 2.94 (1.95-4.41), respectively. Higher loop diuretic dose was particularly associated with increased risk for hospitalization owing to HF: HR 4.80 (2.75-8.37), P < 0.001. The use of loop diuretics was associated with a slightly greater rate of decline in eGFR, which did not vary significantly by diuretic dose.Loop diuretic dose was associated with higher risks of (CV) mortality and predominantly hospitalization owing to HF, which appeared to be higher among those receiving higher daily doses.

For decades the pulmonary circulation was not considered as important as the systemic ("greater") circulation. However, pulmonary hypertension can arise because of many diseases of the heart and lung. Therefore, increasing efforts in research have been undertaken leading to a profound increase in understanding pulmonary vascular physiology and pathophysiology. This review discusses basic physiology, clinical concepts, and treatment options for pulmonary hypertension and the related right ventricular heart failure focusing on secondary pulmonary hypertension in patients during anesthetic procedures. Physiology of Pulmonary Circulation The pulmonary vascular bed is a high-flow, low-pressure circulation system. Pulmonary vessels have less resistance in comparison to the systemic circulation under normal conditions because of higher compliance of pulmonary precapillary arterioles with a thinner media and less smooth muscle cells (SMCs) compared with the corresponding systemic arterioles. In addition, the cross-sectional area of the pulmonary vascular bed is large and highly distensible with recruitable vessels available to accommodate increase in flow resulting in low pressure and low resistance. In contrast to the systemic arteries, pulmonary vessels constrict with hypoxia (Euler-Liljestrand reflex) and relax in the presence of hyperoxia. Furthermore, changes in cardiac output (CO), airway pressure, and gravity affect the pulmonary more than the systemic circulation. Increases in CO distend open vessels and recruit previously closed vessels. Therefore, the cross-sectional area of pulmonary circulation enlarges and results in a decrease in pulmonary vascular resistance (PVR). An increase in CO has very little effect on pulmonary arterial pressure (PAP) because of the recruitment and distension of pulmonary vessels. An increased PAP or left atrial pressure (LAP) may also distend and recruit pulmonary vessels. Clinically, this means that enhanced CO caused by the administration of inotropic drugs or enlarged blood volume will passively decrease PVR. The contribution of intra- and extraalveolar vessels accounts for the unique U-shaped relationship between lung volume and PVR, which is minimal at functional residual capacity and increased at large and small lung volumes (Fig. 1). Clinically, this may be observed when hyperinflation of the lungs greatly increases PVR.Figure 1: Relationship between lung volume and pulmonary vascular resistance (PVR) (123). RV = residual volume, FRC = functional residual capacity, TLC = total lung capacity.Gravity influences the distribution of blood flow in the pulmonary circulation. Blood flow as well as ventilation increases in the dependent areas of the lung. The relationship between alveolar and hydrostatic pressure implies important clinical consequences. Patients with unilateral lung disease should be positioned with the diseased side up as was already shown by Remolina et al. (1). Lying with the sick lung dependent resulted in the worst gas exchange and the lowest arterial oxygen pressure (1). Application of high levels of positive end-expiratory pressure (PEEP) will narrow the capillaries in the well-ventilated lung areas and divert flow to less well-ventilated or nonventilated areas. Therefore, a decrease in PaO2 is the consequence. Constantly changing hemodynamics, mechanical forces, and hormonal environment influence the vascular endothelium and the underlying SMCs. Under normal circumstances, the interaction between endothelium and SMCs results in a low vascular resistance in the pulmonary circulation. An increasing number of molecules seem to be involved in these biochemical transductions: L-arginine-nitric oxide (NO)-cyclic-3′-5′guanosine monophosphate (cGMP) pathway seems to have a predominant role (2). Physiological agonists such as bradykinin and acetylcholine as well as mechanical stress derived from pulmonary blood flow can activate endothelial cells. This results in oxidation of the guanidino-nitrogen atom of the amino acid L-arginine by the constitutive NO synthase to form and release NO. NO diffuses from endothelial cells to the SMCs, and produces relaxation by activating guanylate cyclase with increasing intracellular cGMP (2). Pulmonary endothelial cells (surface area of 200 m2 in the adult) have a very strategic location: they are exposed to the entire CO, link the pulmonary and systemic circulation, and also regulate SMC tone by signaling to the vascular wall. Endothelial cells both seem to sense local shear stress and to initiate a response (e.g., production of NO) in order to accommodate rapid changes of blood flow. NO and prostacyclin (PGI2) support oxygenation and lung inflation in dilating the pulmonary vasculature after birth, keeping a key regulatory role in the lung because of its prompt, local powerful action compared with a brief half-life time (3). Pathophysiology of Pulmonary Hypertension It is now understood that the balance between vasoconstrictors and vasodilators and mitogenic and antimitogenic factors derived from the endothelium is disturbed in situations with an increase in PAP (4, 5). Endothelial dysfunction is promoted by hypoxia, acidosis, free radicals (6), inflammatory mediators, shear stress caused by increased pulmonary blood flow from left-to-right intracardiac shunt (7), and fibrin from thromboembolism (8). There is no widely accepted range for normal PAP. However, mean PAP >25 mm Hg (normal 15 mm Hg) at rest or >30 mm Hg with exercise is generally accepted as indicative for pulmonary hypertension (9). The enhanced pressure in the pulmonary circulation is associated with an increase in PVR and results in a progressive inability of the right ventricle (RV) to sustain its output leading to RV hypertrophy and RV failure depending from acute or chronic changes (4). In a study by Vizza et al. (10), prevalence of RV dysfunction (defined as RV ejection fraction [RVEF] <45%) was significantly higher in patients with pulmonary hypertension compared with all other groups with end-stage pulmonary disease. Determination of PVR is difficult in clinical settings even if the respective variables such as LAP, mean PAP, pulmonary capillary wedge pressure (PCWP), and thermodilution CO are measured directly because of their intrinsic inaccuracies. Therefore, indirect estimations use the equation: Normal PVR is approximately 1.1–1. 4 Wood units or about 90–120 dynes · s · cm−5, and a PVR >300 dynes · s · cm−5 is indicative of pulmonary hypertension. Pulmonary blood flow and volume are not always equal to or correlated with CO, because of intracardiac or other shunts. Vascular Remodeling Chronic pulmonary hypertension leads to structural alterations of the pulmonary vasculature and to a progression of histological changes known as "vascular remodeling" (11). Under physiological conditions, pulmonary arterioles are thin-walled vessels with the media occupying only 7% of the vessel thickness. The major finding in remodeled vessels caused by a chronic stimulus like hypoxia is the increase in SMCs in already muscularized arteries and extension of SMCs into vessels that are normally thin and nonmuscular (12) and thickening of the adventitial layer (13). Thickening of the adventitial layer is the result of marked proliferation of the fibroblasts, which has been shown to be modulated by protein kinase C and mitogen-activated protein kinase (14). After the proliferative response, there is an increase in adventitial connective tissue including a switch in SMC phenotype to a more synthetic cell that is responsible for deposition of increased connective tissue (12). This deposition of most notably collagen is probably a protective mechanism strengthening the vascular wall against the increase in intravascular pressure (15). Additionally, damage to intimal endothelium as well as intimal hyperplasia and fibrosis can be detected (5). The central regulatory function of the pulmonary endothelium is underlined by the fact that a dysfunctional endothelium can influence the development of pulmonary hypertension at the levels of coagulation control, vasomotor tone, and pulmonary vascular remodeling (16). The major stimulus for remodeling is hypoxia (17). The increase in PVR is predominantly caused by the hypoxic pulmonary vasoconstriction (HPV), which resides primarily distal to lobar arteries and proximal to the capillaries and occurs in resistance arterioles 30–300 μm in diameter (18). Pulmonary arteriolar SMC oxygen-sensitive voltage-dependent potassium channels seem to have an important role for initiating HPV (19). Inhibition of these channels by decreased PO2 inhibits outward potassium current, causing membrane depolarization and calcium entry through voltage-dependent calcium channels (19). The main determinant of HPV is alveolar PO2, but mixed venous PO2 contributes to approximately 20% of the response (19). HPV is inhibited by substances such as substance P, atrial natriuretic peptides, by mediators such as PGI2 and NO, by increased LAP, by increased alveolar pressure, and by alkalosis. Enhanced HPV, however, could be observed with acidosis, by using epidural anesthesia and by inhibition of cyclooxygenase or NO synthase (19). Subsequent increases in PAP are predominantly caused by vascular remodeling as well as secondary polycythemia. Proliferation and differentiation of pericytes and intermediate cells to SMCs are a consequence of chronic exposure to hypoxia followed by elastin and collagen synthesis and deposition (20). In addition, vasomotor function may be altered in these remodeled vessels (20). Among the candidates of biochemical mediators of hypoxia-induced pulmonary hypertension are voltage-gated potassium channels, mitochondrial oxygen sensing, and an imbalance in vasoactive factors (see below) (21). Remodeling also happens in inflammation secondary to sepsis (22) and in patients with chronic lung disease (23) and adult respiratory distress syndrome (ARDS) (24). The inflammation process and increased blood flow lead to vascular remodeling by damaging endothelial cells and disturbs the sensitive balance of pulmonary tone. Under physiological conditions, these cells eliminate factors that initiate SMC proliferation such as angiotensin II, endothelin, thromboxane A2, prostaglandin H2 and O2−(25). Alternatively, damaged endothelial cells may fail to produce inhibitory factors, possible heparin-like substances, which normally decrease SMC proliferation. Removal of the inciting stimulus can lead to reversal of structural changes. Etiology of Pulmonary Hypertension Pulmonary hypertension is caused by a variety of acute and chronic pulmonary diseases with an increase in PAP (Table 1). In contrast to secondary pulmonary hypertension, primary pulmonary hypertension (PPH) is not related to a known underlying disease.Table 1: World Health Organization Diagnostic Classification of Pulmonary Hypertension (1998) (21)PPH PPH is rare (1–2 per million in the general population), affects more women than men (1.7:1), sometimes has a familial link (6% of all cases), and has a poor prognosis (median survival 2–3 yr after diagnosis). PAP usually is >60 mm Hg in these patients (9, 26). PPH is a diagnosis of exclusion, because it is idiopathic. Hypoxemia and increased PVR resulting in an increased PAP can lead to RV failure and death. Altered vasoreactivity alone is not responsible for PPH. Vascular remodeling contributes to the vasculopathic process. However, regression of extensive changes caused by hypertension can occur. Secondary Pulmonary Hypertension Secondary pulmonary hypertension is more common, the increases in PAP are generally less severe (mean PAP <40 mm Hg) (26), and it is also more frequently seen in the perioperative period. Therefore, in this review, we have focused on secondary forms of pulmonary hypertension. Most cases of pulmonary hypertension are secondary to cardiac or pulmonary disease (Table 1) and may be reversible in some cases. Clinical manifestations might be overshadowed by the symptoms of the underlying disease (Table 2). Blood vessel changes are not confined to PPH but are also found in many forms of secondary pulmonary hypertension. Congenital cardiac disease with an atrial or ventricular septal defect causes an increase in pulmonary blood flow. Over time, in response to the increased blood flow, the PVR is increased and eventually will exceed systemic vascular resistance (SVR). Under these conditions, blood flow is shunted from right to left, often referred to as Eisenmenger syndrome. In contrast, high-pressure shunts such as those associated with truncus arteriosus, ventricular septal defects, or patent ductus arteriosus (28) cause pulmonary hypertension much earlier and it is often more severe.Table 2: Common Symptoms and Signs of Pulmonary Hypertension (27)The relevance of pulmonary hypertension in the perioperative period was shown in a study by Reich et al. (29). In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB), the development of pulmonary hypertension was a significant predictor of increased mortality and perioperative myocardial infarction (29). The severity of the observed vasoconstriction correlates with the extent of CPB-induced endothelial injury (30). Levels of thromboxane A2(31) and endothelin (32) were increased after CPB, whereas PGI2 and NO levels were reduced (33). For a long time, it was thought that CPB did not cause any pulmonary endothelial injury due to ischemia-reperfusion because of the protection via the vasa vasorum of the bronchial circulation. It has been shown, however, that total CPB may cause complete cessation and reestablishment of pulmonary artery flow, with inadequate pulmonary endothelial blood supply by the vasa vasorum, resulting in an ischemia-reperfusion injury (34). The intraoperative injury and postoperative endothelial dysfunction of the pulmonary endothelium is promoted by the following factors (2): Preoperative status of the pulmonary vascular bed, i.e., pulmonary hypertension, valvular pathology; chronic obstructive pulmonary disease, pulmonary thromboembolism, and shear stress caused by increases in pulmonary blood flow and pressure of left-right intracardiac shunt. Bando et al. (35) demonstrated in patients with congenital heart disease that preoperative pulmonary hypertension, absence of mixed venous saturation monitoring, and absence of prophylactic α-blockade significantly increased postoperative pulmonary hypertension. Intraoperative vasospastic stimuli, such as hypoxia, hypercarbia, acidosis, duration of total CPB, ischemia-reperfusion injury, free radical formation, inflammatory mediators, pulmonary leukosequestration, excess thromboxane or endothelin production, and microemboli. Postoperative factors such as adrenergic tone, atelectasis, and HPV. Other examples of pulmonary hypertension during anesthesia are shown in Table 3.Table 3: Occurrence of Pulmonary Hypertension During Anesthesia (36)Symptoms and Diagnosis of Pulmonary Hypertension The most common clinical signs of pulmonary hypertension are dyspnea and fatigue (9) (see also Table 2). These major symptoms might be explained through the associated decrease in CO; however, an exact etiology is still missing. On physical examination, a prominent P2 heart sound, a tricuspid regurgitation murmur, an atrial (S3), or ventricular (S4) heart sound might be heard. The chest radiograph can display an enlarged main pulmonary artery and enlarged hilar vessels, whereas the electrocardiogram shows a right axis deviation suggesting right ventricular hypertrophy. However, the validity of acute changes in the electrocardiogram attributed to right heart insufficiency in the intraoperative period is limited. Transesophageal echocardiography (TEE) as a more advanced technique diagnoses pulmonary hypertension indirectly attributed to RV enlargement, paradoxical interatrial and interventricular movement, partial systolic closure of pulmonary valve, tricuspid regurgitation, and an increased RV systolic pressure (Fig. 2). There are two approaches to obtaining hemodynamic measurements using TEE. By using spatial imaging methods, cardiac chamber volumes can be estimated to obtain both preload and stroke volume. In addition, Doppler-based methods can be used to estimate both right ventricular filling and CO (37). Because of the inherent difficulty in developing a simple geometric model of the RV, regression equations may inaccurately predict ventricular volumes. In addition, TEE measurements are further altered by changing loading conditions, which alter both the size and geometry of the RV. Although TEE evaluation of RV volume can be difficult to determine in adults, high-quality images are routinely obtained in pediatric patients. One of the main limitations on further use of TEE is the availability of equipment as well as costs of echocardiography machines and probes, and expertise (37). The definitive diagnosis is obtained by right heart catheterization with direct measurement of PAP, right atrial pressure (RAP), PCWP, and CO.Figure 2: Transesophageal echocardiography for diagnosis of pulmonary hypertension. Dilated right ventricle (RV) in the midesophageal four chamber view. The figure shows the classical septal (S) interventricular shift to the left side. RA = right atrium, LA = left atrium, LV = left ventricle.RV and Pulmonary Hypertension Like the pulmonary circulation, the RV was not considered as important as the left ventricle (LV) in maintaining normal hemodynamics and counted for a long time as a "quantite negliable" (38). Today it is recognized that RV and LV are interdependent and both have vitally important functions. The RV is a thin-walled, highly compliant, but poorly contractile chamber. Under normal loading conditions and when function is not compromised, RV ejects blood against 25% of the afterload of the LV, resulting in a smaller RV wall thickness (39). The RV is bound by the RV free wall and the interventricular septum. Failure of the septum (e.g., because of ischemia) to contract normally will decrease RV systolic function. Blood supply for the RV and the septum depends mostly on whether a right or left dominant, or a "balanced" coronary circulation is present. Usually the right and the left anterior descending coronary artery supply the septum and parts of the free wall of the RV. The continuous pressure gradient between the aorta and the RV (coronary perfusion pressure) is responsible for the coronary blood flow to the RV free wall throughout systole and diastole (40). Therefore, the RV blood/oxygen supply is proportional to the systemic pressure but inversely proportional to the RV pressure. Systemic hypotension or increased RV pressure results in a decreased RV coronary perfusion pressure (41). Vlahakes et al. (42) previously showed that right heart performance is directly related to systemic pressure during pulmonary hypertension. RV function is very sensitive to increased RV preload or afterload, septic shock, coexistent LV dysfunction, or right coronary artery occlusive disease (43, 44). In a fundamental study, Urabe et al. (45) demonstrated that an increase in the afterload of the RV resulted in a rightward shift of the relationship between perfusion pressure and regional shortening. Also, end-diastolic segment lengths increased significantly after banding of the pulmonary artery. In contrast to LV performance, RV function is relatively sensitive to increases in afterload. Acute increase in mean PAP above approximately 40 mm Hg results in a significant decrease in RVEF even in the presence of a normal RV contractility. However, gradual increases in afterload are well tolerated, because the RV has time to assemble new sarcomeres in parallel to increase wall thickness (39). In the presence of decreased RV contractility, the RV is even more susceptible to acute increases in afterload. The decrease in RVEF results from a disproportionate increase in end-systolic volume compared with end-diastolic volume (41). The RV is less preload-responsive than the LV such that a given increase in preload results in a smaller increase in stroke work. Therefore, attempts at volume loading may be less effective in increasing RV output compared with volume loading of the In addition, volume loading may even the of RV oxygen (41). Vlahakes that two important in the of right heart RV afterload be reduced and systemic pressure be or Normal and are for maintaining normal RV function The of is as important for RV as it is for LV RV performance is by both intrinsic factors of the RV as well as factors afterload, of the pressure, right coronary artery perfusion pressure, LV performance, and the contractile of the interventricular of the LV function like coronary artery disease, heart valvular heart disease, or systemic hypertension influence RV function by ventricular Also, a RV and right can shift the interatrial and interventricular septum and the left and LV end-diastolic volume. venous pressure not on RV filling pressure and volume because it is dependent on the compliance of the RV in the tricuspid methods, and imaging are and more in the RV RV dysfunction caused by increased PAP was demonstrated in patients with chronic pulmonary disease and in patients ventilation can also RV the interventricular septum paradoxical resulting in right heart and decreased LV chamber size In postoperative a decrease in RVEF is observed at levels because of of alveolar vessels and increase in RV afterload significant was between RVEF and increasing of airway pressure by ventilation of the underlying disease has Because symptoms often arise in pulmonary hypertension, the after of signs of RV insufficiency is yr in for lung disease, as well as systemic for chronic lung are of of pulmonary hypertension. of which causes and and for can also definitive of congenital heart diseases can and mortality from postoperative pulmonary hypertension common clinical is the of the right heart because of chronic left heart In this of the LV has of the right heart by means of coronary or coronary artery bypass treatment and should PVR, which can be with the following and factors the pulmonary oxygenation with oxygen of respiratory acidosis, mm Hg) of a to of respiratory of the lung of release caused by stress and of options for RV dysfunction with increased PVR whereas positive inotropic drugs are the treatment of in RV dysfunction with normal PVR. of RV of RV preload should be considered if central venous pressure is mm Hg It is however, that preload of the RV should be estimated by a simple volume in an increase in mean arterial blood pressure and can increase RVEF with volume if RV is normal and PAP is increased only However, administration of volume also can have in patients with right heart treatment in for (defined as patients no increase in to the with central venous pressure mm of RV of the of the pulmonary circulation of CO and RV failure previously or vasodilators should be keeping in to a significant decrease in the decrease in the in RV stroke volume, systemic hypotension can be the consequence. is thought to produce by calcium channels has other such as the to NO synthase activate and release in both endothelial and SMCs. of SMCs is by both release of NO and direct of SMCs has a half-life it is relatively for the pulmonary circulation. It has been shown to be a and of other drugs to produce pulmonary in of patients with PPH a but there are no observed because of the small In contrast to treatment with that to reduced PAP and PVR in patients with secondary pulmonary hypertension treatment did not any This might be explained by the fact that on their to vascular remodeling The angiotensin reduced PAP and PVR in patients with secondary pulmonary hypertension 4 after have been shown to be effective in the treatment of pulmonary hypertension secondary to connective tissue vascular disease but not in patients with treatment was because of the on venous The of with calcium in secondary pulmonary hypertension seems to on the of PAP, i.e., the higher the of PAP, the less effective the of to the of on PAP in patients with pulmonary showed that a in PAP in of The in PAP in patients with the and the in PAP with clinical Although these drugs have shown their they have severe if used it is that calcium treatment should be to to Patients with pulmonary hypertension and severe clinical right heart failure (mean mm CO should be from treatment with calcium because of the inotropic of these by or more responsible for the of monophosphate leading to an increased of these with increased LV and pulmonary given have been used in patients with pulmonary hypertension after cardiac was shown for cardiac patients with increased PVR to pulmonary systemic It also seems to have an pulmonary effect to The PGI2 was in to PAP in PPH It is by the vascular endothelium and via prostaglandin to cyclase with following increase of PGI2 production is in patients with pulmonary hypertension of PGI2 may in to these are an inhibition of both and SMC proliferation from treatment of PGI2 or its also PAP in pulmonary hypertension of the pulmonary hypertension after heart in or pulmonary hypertension secondary to connective tissue diseases in a

BackgroundPulmonary hypertension (PH) is most commonly caused by left-sided heart disease and may negatively affect the long-term prognosis and quality of life of patients with chronic heart failure (CHF). CardioMEMS (Micro-Electro-Mechanical-System) allows physicians to monitor pulmonary artery (PA) pressures remotely and optimize heart failure treatment based on haemodynamic parameters, which provides further insight into the effect of valvular interventions.Case summaryWe present a case of a 61-year-old male patient with an ischaemic cardiomyopathy, poor LV function, moderate to severe mitral regurgitation, and severe aortic valve regurgitation in refractory heart failure. Right heart catheterization and CardioMEMS monitoring revealed severe pulmonary hypertension with mean PA pressures of 55 mmHg and a mean pulmonary capillary wedge pressure of 21 mmHg despite up titration of heart failure medication and sildenafil. Pulmonary and systemic causes of pulmonary hypertension were excluded. After heart team consensus, the patient underwent transcatheter aortic valve implantation (TAVI) which resulted in normalization of PA pressures and a significant improvement of functional performance.DiscussionTo the best of our knowledge, this is the first case report describing the direct effects of TAVI on continuous PA pressures in a patient with poor LV function and severe aortic regurgitation. Elective TAVI appeared to be safe and very effective in reverting severe pulmonary hypertension. Most strikingly, drug interventions could not affect the elevated pulmonary pressures, but TAVI corrected the aortic valve insufficiency with normalization of left-sided pulmonary hypertension.

Background: Guideline-directed medical therapy in patients with systolic heart failure (HF) has demonstrated improvement in morbidity and mortality rates. The FDA approved sacubitril/valsartan in 2015 to reduce the risk of cardiovascular death and hospitalization for HF.Objective: The purpose of this study was to evaluate the change in loop diuretic dose and the clinical outcomes of angiotensin receptor-neprilysin inhibitor (ARNI) therapy within a 90-day follow-up period.Methods: A retrospective chart review of 110 HF patients on concomitant ARNI and loop diuretic therapy at New York University Langone Health was conducted. The primary endpoint was a change in loop diuretic dose. Six secondary endpoints, including dose conversion from ACEi or ARB to ARNI therapy, were assessed.Results: Of the 110 HF patients, 72 did not receive diuretic dose adjustments, yet 40 (55.56%) experienced laboratory-dependent dehydration. Fifty-six percent of patients experienced an improvement in systolic blood pressure, and 52 percent experienced a decrease in diastolic blood pressure. Sixty percent of patients experienced an improvement in EF, with a median increase of 10.00% over a 90-day follow-up. A significant negative correlation between patients’ age and absolute change in EF was identified (r= -0.28; p < 0.05), indicating that the increase in EF was stronger for younger patients. Eighteen hospitalizations occurred within a 90-day follow-up, with only 4 patients being admitted for heart failure exacerbation.Conclusion and Relevance: This study examines the real-world effects of ARNI therapy in patients with systolic heart failure. Optimization of HF medications, including ARNI therapy, remains an important factor for achieving the maximum benefits in heart failure management. ARNI therapy requires careful monitoring to ensure effective diuresis in symptomatic heart failure patients while avoiding adverse events. Future studies should address diuretic dose adjustment in conjunction with the administration of ARNI and sodium-glucose cotransporter-2 inhibitors.

Application of health data analytics in pharmacy: An innovative approach to developing a heart failure dashboard.

Heart failure has been suggested to increase the risk of developing diabetes. We investigated the relation between heart failure severity, defined by loop-diuretic dosage, and the risk of developing diabetes in a nationwide cohort of patients with heart failure. We followed all Danish patients discharged from hospitalisation for first-time heart failure in 1997-2010, without prior use of hypoglycaemic agents, until a claimed prescription for hypoglycaemic agents, death or 31 December 2010. The association of loop-diuretic dosage (furosemide equivalents) 90days after discharge (study baseline) with risk of diabetes was estimated by multivariate Cox regression models. In total, 99,362 patients were included and divided into five loop-diuretic dose groups: 30,838 (31%) used no loop diuretics; 24,389 (25%) used >0-40mg/day; 17,355 (17%) used >40-80mg/day; 11,973 (12%) used >80-159mg/day; and 14,807 (15%) used ≥160mg/day. A total of 7,958 patients (8%) developed diabetes. Loop-diuretic dosages were associated with an increased risk of developing diabetes in a dose-dependent manner. Concomitant use of renin-angiotensin system inhibitors (RASis) attenuated the risk (p value for interaction <0.0001). Compared with patients using no loop diuretics (group 1), the adjusted HRs (95% CI) for developing diabetes for groups 2-5 respectively were 1.16 (1.07, 1.26), 1.35 (1.24, 1.46), 1.48 (1.35, 1.62) and 1.76 (1.61, 1.92) with RASi treatment, and 2.06 (1.83, 2.32), 2.28 (2.01, 2.59), 2.88 (2.52, 3.30) and 3.02 (2.66, 3.43) without RASi treatment. In a nationwide cohort of patients with heart failure, severity of heart failure was associated with a stepwise increased risk of developing diabetes. Increased awareness of risk of diabetes associated with severe heart failure is warranted.

Background: Diuretic resistance is commonly reported in acute heart failure (AHF), especially in patients presenting with impaired kidney function. Effective treatment strategies for promoting decongestion in this population remain unclear. Methods: A systematic review using MEDLINE/Cochrane databases was performed from inception to January 2024, identifying randomized clinical trials (RCTs) including patients with diuretic resistance or at risk of diuretic resistance based on the presence of kidney dysfunction at study enrollment. Trials testing different pharmacological or invasive modalities compared to standard of care, placebo or an active comparator were considered. Data on decongestion-related outcomes, safety outcomes, and clinical outcomes up to 90 days were collected. Results: Among the 22 RCTs included, 6 trials involved 529 patients with established diuretic resistance, while 16 trials enrolled 1,913 patients at risk of diuretic resistance. Diuretic resistance was differently defined across studies and most trials focused on interventions targeting different sites of action along the renal tubules. The different treatment strategies demonstrated efficacy in promoting decongestion while being associated with a mild increase in creatinine and cystatin C. The use of appropriately high doses of intravenous loop diuretics was able to promote decongestion across the spectrum of kidney dysfunction. The presence of baseline kidney dysfunction did not identify a population resistant to standard decongestive strategies. Conclusions: Diuretic resistance is not accurately defined in AHF but is uncommon in patients treated with appropriately high doses of intravenous loop diuretics. The main therapeutic goal in the acute setting should focus on promoting decongestion instead of overemphasizing on mild changes in kidney-related biomarkers.

Rescuing the right ventricle: A conceptual framework to target new interventions for patients receiving a durable left ventricular assist device

AimsTo assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial.Methods and resultsOverall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post‐randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on‐treatment analysis.ConclusionTreatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

Plasma B-type natriuretic peptide (BNP) is an established prognostic indicator in patients with left ventricular systolic heart failure (LHF). However, no efficient data exist regarding the differences in plasma BNP activity between patients with biventricular heart failure and those with right heart failure (RHF) due to chronic obstructive pulmonary disease (COPD). This study investigates BNP in RHF due to COPD in comparison to RHF due to LHF, and estimates the relation of BNP levels with clinical and echocardiographic parameters. We evaluated plasma BNP in 88 patients admitted to hospital with acutely decompensated chronic heart failure (31 with RHF due to LHF, 30 with RHF due to COPD without left heart disease, and 27 with LHF without right ventricular involvement). All patients underwent echocardiography examination and blood samples were collected to determine BNP and routine blood chemistry measurements. Plasma BNP levels were significantly higher in RHF due to LHF compared with RHF due to COPD (P <0.001). Plasma BNP did not appear to differ between RHF due to LHF and LHF alone (P = 0.802). In multiple linear regression analysis, tissue Doppler imaging e(LV) (B: -0.053, P = 0.002) and e(RV) (B: -0.079, P = 0.007) had an independent negative association with BNP, whereas logUrea (B: 0.635, P < 0.001) and hematocrit (B: 0.014, P = 0.005) showed an independent positive association with BNP levels in the group of RHF due to COPD. BNP levels were significantly lower in RHF due to COPD compared with RHF due to LHF and were independently predicted by indices of left ventricular and right ventricular diastolic function, renal function, and anemia.

Recurrent orthostatic syncope due to left atrial and left ventricular collapse after a continuous-flow left ventricular assist device implantation

A New Classification of Pulmonary Hypertension