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At least 19 recordsLinked to original sources
PubMed2025

Angiotensin-Neprilysin Inhibition and Left Ventricular Assist Device Therapy: Primary Results of the ENVAD-HF Trial.

BACKGROUND: The role of heart failure-specific therapies in left ventricular assist device (LVAD) recipients is unclear, and observational data suggest improved outcomes with neurohormonal blockers. OBJECTIVES: ENVAD-HF (Multicenter, Randomized, Open-Label, Parallel Group, Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients) sought to evaluate the safety and tolerability of the angiotensin-neprilysin inhibitor sacubitril/valsartan vs standard of care (SOC) for managing blood pressure (BP) in HeartMate 3 LVAD recipients. METHODS: ENVAD-HF was a prospective multicenter, randomized, open-label study of sacubitril/valsartan vs SOC for managing BP (mean arterial pressure goal: 75-90 mm Hg) in stable LVAD recipients with 12-month follow-up. The composite primary endpoint was time to death, deterioration in renal function, hyperkalemia, or symptomatic hypotension leading to drug withdrawal. Exploratory endpoints included clinical and biomarker assessments and patient-reported outcomes. RESULTS: In 60 randomized patients (30 in each arm), sacubitril/valsartan compared with SOC demonstrated an HR of 0.42 (95% CI: 0.08-2.18; P = 0.30) for the primary endpoint at 12 months. Two primary endpoints were reached in the sacubitril/valsartan group (1 death and 1 symptomatic hypotension event) compared with 5 in the SOC group (2 deaths, 2 worsening renal function events, and 1 symptomatic hypotension event). Numerical trends in favor of sacubitril/valsartan were noted for other exploratory endpoints, including a reduced number of BP medications (difference: -1.09 [95% CI: -1.52 to -0.66]; P < 0.0001) and a significantly better Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (improvement: +10.6 [95% CI: 2.6-18.7]; P = 0.011). CONCLUSIONS: ENVAD-HF, a prospective randomized controlled trial of angiotensin-neprilysin inhibition in stable HeartMate 3 LVAD recipients, demonstrated the safety and tolerability of this therapy in this unique population. The trial forms the basis for a pivotal trial to investigate the usefulness of HF-specific therapies in the LVAD population. (Sacubitril/Valsartan in Left Ventricular Assist Device Recipients [ENVAD-HF], NCT04103554; A multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients, 2019-003888-22).

Humans↗
PubMed2005

[Combined therapy with quinapril, an ACE inhibitor, and valsartan, a type 1 angiotensin II receptors blocker, for moderate chronic cardiac failure may raise the degree of neurohormonal block and improve 24-h heart rate variability compared to the effect of monotherapy (data from the trial SADKO-CHF)].

AIM: To compare effects of various regimens of long-term monotherapy with quinapril (an ACE inhibitor) and valsartan (a type 1 angiotensin II receptors blocker) and combined therapy with these drugs on the activity of heurohormonal systems and 24-h heart rate variability (HRV) in patients with stable moderate chronic cardiac failure (CCF). MATERIAL AND METHODS: A total of 80 patients with FC II-III CCF secondary to coronary heart disease (CHD), delated cardiomyopathy (DCMP) and decompensated hypertensive heart (49%/47%/4%) were randomized into 3 groups. Group 1 patients (n = 28) received quinapril, group 2 (n = 26)--valsartan, group 3 (n = 26)--quinapril + valsartan. The levels of norepinephrine (NE), angiotensin II (AT II), activity of plasmic renin (PR), aldosteron (AS), plasmic cerebral sodiumuretic peptide (CSUP) were measured and ECG with determination of HRV and heart rate disturbances was made before and 3, 6 months after the treatment. RESULTS: NE concentration lowered most significantly in group 1 (from 630 to 405 pg/ml) vs groups 2 and 3 (from 525 to 490 pg/ml and from 525 to 480 pg/ml, respectively). A 6-month treatment induced significant changes neither in concentrations of AT II nor AC. ATII concentrations rose 2-fold in group III (from 11.9 to 24.3 pg/ml) under a parallel rise of PR activity from 0.7 to 2.5 ng/ml/h and a fall in AS level from 132 to 83 pg/ml. In group 2 AS diminished also (from 165 to 126 pg/ml). CSUP decreased in all the groups, but significantly only in groups II and III (from 350 to 237 and 322 to 204 pg/ml after 6 months of treatment, respectively). Significant changes of 24-h HRV (both spectral and temporary) were observed in group 1 after 3 months of treatment. These changes lost significance to the end of the treatment. In groups 2 and 3 the changes were less pronounced. CONCLUSION: Quinapril is more potent than valsartan and quinapril + valsartan combination in relation to activity of sympathico-adrenal system and HRV in patients with moderate stable CCF. Long-term therapy with valsartan does not improve parameters of HRV in moderate CCF. If CCF patients take quinapril for a long time, they develop the effect of disappearing block of AS synthesis and reactivation of A TII production. The best mechanism of long-term control over the activity of renin-angiotensin-aldosteron system in patients with moderate CCF is combination of quinapril with valsartan.

Adult↗
PubMed2004

Neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy.

OBJECTIVES: Activation of the neuroendocrine axis in congestive heart failure is of prognostic significance, and neurohumoral blocking therapy prolongs survival. The hypothesis that surgical reduction of left ventricular size and function decreases neuroendocrine activation is less established. We evaluated the neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy. METHODS: Norepinephrine, plasma renin activity, and angiotensin II were measured in 10 patients before and 12 months after left ventricular reconstruction. In an additional 5 patients, brain natriuretric peptide was measured before and 3 months postoperatively. Three-dimensional cardiovascular imaging was used to assess ejection fraction and left ventricular end-diastolic volume index. RESULTS: Concurrent with improvements of New York Heart Association functional class (2.9 +/- 0.5 preoperatively vs 2.0 +/- 0.4 postoperatively, P <.001), ejection fraction (23.9% +/- 6.6% vs 36.2% +/- 6.2%, P <.01), and left ventricular end-diastolic volume index (140.8 +/- 33.8 mL/m(2) vs 90.6 +/- 18.3 mL/m(2), P <.01), considerable reductions were observed for median plasma profiles of norepinephrine (562.0 pg/mL vs 319.0 pg/mL, P <.05), plasma renin activity (5.75 microg/L/h vs 3.45 microg/L/h, P <.05), angiotensin II (41.0 ng/mL vs 23.0 ng/mL, P =.051), and brain natriuretric peptide (771.0 pg/mL vs 266.0 pg/mL, P <.05). The more plasma renin activity or angiotensin II decreased after left ventricular reconstruction, the higher was the increase in ejection fraction (R = -.745, P <.05 [plasma renin activity]; R = -.808, P <.05 [angiotensin II]). CONCLUSIONS: Surgical improvements of ejection fraction and left ventricular end-diastolic volume index by left ventricular reconstruction were accompanied by improvement of both the neuroendocrine activity and the functional status in patients with congestive heart failure. Whether this favorable neurohormonal response is predictive of an improved survival requires further evaluation.

Aged↗
PubMed1993

Pathophysiologic and pharmacologic rationales for clinical management of chronic heart failure with beta-blocking agents.

An understanding of the important role of neurohormonal compensatory mechanisms in heart failure has been translated into therapeutic options that can improve cardiac function, alter disease progression, and improve survival. Angiotensin-converting enzyme inhibitors are of proven benefit in this regard, and beta-adrenergic receptor antagonists are potentially another such class of agents. By inhibiting the myocardial effects of chronic adrenergic activation, beta blocking agents may improve left ventricular function or delay its deterioration in patients with heart failure. Aside from blocking beta-adrenergic receptors, other ancillary properties inherent in third-generation beta-blocking agents (such as vasodilation) may exert additional favorable effects. Clinical data generated in subjects with heart failure indicate that beta-antagonist therapy exerts its physiologic and clinical effects through neurohormonal antagonism, generally analogous to angiotensin-converting enzyme inhibitors. Virtually all controlled long-term studies show that beta-blocking agents improve cardiac function and hemodynamics in patients with chronic heart failure, but large-scale trials are needed to ascertain a favorable effect on the natural history of heart failure.

Adrenergic beta-Antagonists↗
PubMed1994

Left ventricular function and prognosis after myocardial infarction: rationale for therapeutic strategies.

Prognosis after acute myocardial infarction is strongly associated with left ventricular dysfunction. However, asynergy does not necessarily imply loss of viability and myocardial necrosis. In fact, two different patterns of contractile dysfunction, possibly coexisting, have been shown after acute myocardial infarction: Stunning and hibernation represent distinct patterns of contractile dysfunction that share the character of reversibility. It is noteworthy, then, to identify the presence of these two conditions at the bedside and to develop medical treatment to effect recovery of myocardial dysfunction. This strategy has the potential to ameliorate the outcome of patients after acute myocardial infarction by improving left ventricular function. Beta-blocker therapy significantly reduces mortality and the incidence of reinfarction after an acute myocardial infarction: These benefits result from the prevention of sudden death, the reduction of the extent of myocardial injury during the acute phase, and a further antiischemic action. Nevertheless, beta-blocker therapy increases left ventricular dilatation. Recent experimental and clinical data show that ACE inhibitors confer positive therapeutic effects after myocardial infarction by reducing the extent of left ventricular dilation, by reducing mortality, and by improving the clinical outcome. Not all patients, however, can be subjected to this therapeutical approach because of the possible detrimental effects produced by hypotension and by block of neurohormonal activation, sometimes truly compensatory in the early phase. Therefore, it would be interesting to suggest a combination therapy of a beta-blocker with a vasodilator agent (ACE inhibitor or calcium-channel blocker.

Clinical Trials as Topic↗
PubMed2000

Beta-blockers and spironolactone in heart failure.

Neurohormonal antagonism is now recognized as an essential treatment modality for heart failure. As a prime example, the benefits of blocking the renin-angiotensin system with angiotensin converting enzyme inhibitors are clearly established for all four New York Heart Association classes. In this clinical trials review, we discuss two other therapies with neurohormonal targets: beta-blockers and the sympathetic nervous system, and the aldosterone antagonist spironolactone.

Adrenergic beta-Antagonists↗
PubMed1998

Innovations in the pharmacologic management of heart failure.

Improved understanding of the pathophysiologic course of heart failure has led to many advances in pharmacologic therapy. Angiotensin-converting enzyme inhibitors represent the first effort at targeting neurohormonal activation in chronic heart failure. More recently, beta-adrenergic receptor antagonists have been shown effective in blocking chronic sympathetic nervous system activation. The roles of digoxin and the newer, vasoselective calcium channel blockers in heart failure have been better defined. Other agents targeting the neurohormonal system are under investigation. These include angiotensin-receptor antagonists, aldosterone inhibitors, and endothelin antagonists. Experience with phosphodiesterase inhibitors and adrenergic agents has confirmed the importance of neurohormonal activation in progression of heart failure. Despite angiotensin-converting enzyme inhibitor, diuretic, and digoxin therapy, mortality in heart failure remains high. Careful manipulation of the neurohormonal response to heart failure holds promise for altering the course of the disease.

Adrenergic beta-Antagonists↗
PubMed2003

Vasopressin receptor antagonists. Therapeutic potential in the management of acute and chronic heart failure.

Despite the use of ACE inhibitors and beta-blockers, the morbidity and mortality of patients with chronic heart failure remains quite high. This has stimulated the development of new therapies, many based on the neurohormonal hypothesis. There are now multiple agents being developed for the treatment of heart failure designed to block many of the neurohormones that are increased in these patients. One of the hormones that is increased in chronic heart failure is vasopressin. Vasopressin reduces free water secretion and at high concentrations, causes vasoconstriction in the peripheral vasculature. Antagonists to vasopressin will promote free water excretion (aquaresis) and vasodilatation with a subsequent reduction in afterload. In theory, these agents would be beneficial for both acute exacerbations of heart failure (free water excretion) and chronic heart failure (neurohormonal blockade). We review the potential uses of these antagonists for these two conditions and the promising results of small, hemodynamic trials with the new vasopressin antagonists that have already been performed.

Acute Disease↗
PubMed2005

Emerging trends in the management of heart failure: Beta blocker therapy.

There is overwhelming evidence that beta blocker therapy in the form of metoprolol, bisoprolol, and carvedilol can have positive outcomes on morbidity, mortality, and quality of life in patients who have been diagnosed with mild to severe heart failure. Barring contraindications, beta blockers should be considered a cornerstone of therapy for these patients along with ACE inhibitors and diuretics. Beta blocking drugs are effective in modifying the cascade of events that occur as a result of the neurohormonal response that leads to the devastating effects evident during heart failure. Long-term effects of beta blockade include an increase in cardiac output, an increase in exercise tolerance, a decrease in the number of hospitalizations, and an overall improvement in symptoms.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Congestive heart failure: potential role of arginine vasopressin antagonists in the therapy of heart failure.

Neurohormonal imbalances clearly contribute to the pathophysiology of chronic congestive heart failure. Agents that interfere with the generation or effects of angiotensin II and aldosterone, or which block the effects of excess sympathetic drive, all favorably affect mortality. Arginine vasopressin, through its V(1A) and V(2) receptor-mediated effects, could theoretically also contribute to progression of left ventricular dysfunction and heart failure by aggravating systolic and diastolic wall stress, and by directly stimulating myocardial hypertrophy. Arginine vasopressin levels are increased in congestive heart failure patients; acutely, both V(1A) and V(2) antagonists produce beneficial hemodynamic responses in both clinical and experimental congestive heart failure. Experimental studies also indicate beneficial effects of V(1A) and V(2) antagonists (alone or in combination) on hemodynamics and possibly ventricular remodeling after myocardial injury. Currently, there are no long-term studies of any type of arginine vasopressin antagonist in human heart failure, but both the theoretical rationale and preclinical data would appear to justify such efforts.

Animals↗
PubMed2000

Neurohormonal factors in heart failure.

Currently there are 4 to 5 million people with congestive heart failure in the United States. They consume greater than 7% of the total health care dollar of which a significant portion is directly related to hospitalization expenses alone. Most patients with chronic congestive heart failure can be managed efficiently outside the hospital setting by the proper use of nonpharmacologic therapies. Neurohormonal pathways have a significant impact on the progression of congestive heart failure. Medications, which include alpha-blockers, beta-blockers, digoxin, spironolactone, and diuretics, now can block, modify, or manage most of these neurohormonal effects, and therefore, have a stabilizing effect on the patient with congestive heart failure. Understanding the physiology and medications involved for optimal treatment of congestive heart failure is a must to ensure the quality of life that these patients deserve.

Aldosterone↗
PubMed1996

Beta-adrenoceptor blocking agents for the treatment of heart failure.

Congestive heart failure is associated with high morbidity and mortality. Modification of neurohormonal activation by use of angiotensin converting enzyme inhibitors has been shown to decrease symptoms and prolong survival. More recent evidence has suggested that beta-adrenoceptor blocking agent therapy may be also beneficial in patients with congestive heart failure, possibly by down-regulating the activation of the adrenergic system. A large number of randomized trials of beta-adrenoceptor blocking agents in heart failure have been performed. These studies demonstrated improvement in symptoms of congestive heart failure, functional classification, and reduction in the number of patients requiring cardiac transplantation. beta-adrenoceptor blocking agents have not been shown to decrease mortality, however, the current trials have been too small to be conclusive in this regard.

Adrenergic beta-Antagonists↗
PubMed1998

Neurohumoral activation and progression of heart failure: hypothetical and clinical considerations.

The model for heart failure has changed radically over the past 20 years. No longer a simple hemodynamic paradigm of pump dysfunction, heart failure is now characterized as a complex clinical syndrome with release of many neurohormones and cytokines, which are believed to be most responsible for progression of disease. This change in our understanding of the pathophysiology of heart failure has important therapeutic implications. Drugs designed to influence the myocardial contractile state have been found over the past few decades to have either a neutral or an adverse effect on long-term survival, whereas agents designed to block the renin-angiotensin-aldosterone and other neurohormonal systems have proved to be remarkably effective treatment. Recently, drugs designed to block excessive sympathetic nervous system activity have been demonstrated in well-controlled studies to be safe and effective forms of therapy for heart failure. Carvedilol, a nonselective beta-adrenergic blocker with alpha1-blocking and antioxidant properties, is associated with prevention of progression of heart failure as manifested by improvement in left ventricular (LV) function, reduction in heart size, and improved survival in patients with New York Heart Association functional Class II and III symptoms. This improvement is observed equally in patients with ischemic and non-ischemic heart failure. It is tempting to speculate that beta-adrenergic blockers prevent the progression of heart failure by reducing LV mass and LV chamber size. In essence, carvedilol, and perhaps other beta-adrenergic blockers, appear to abrogate relentless LV remodeling which is typically associated with progression of heart failure. The combination of angiotensin-converting enzyme inhibitors and beta-adrenergic blockers may be particularly effective in this regard, although more data on beta-adrenergic blockers in patients with advanced heart failure are needed. Data from experimental heart failure animal models also suggest that endothelin (ET) subtype A (ET(A)) receptor blockers have the potential to lessen the pace of progressive LV remodeling. As our understanding of the neuroendocrine response to diminished cardiac performance improves, novel and even more imaginative neurohormonal and cytokine antagonists are likely to emerge as important new treatments for both hypertension and heart failure.

Adrenergic beta-Antagonists↗
PubMed1986

[Stimulation or blocking of the periurethral region--an expansion of conservative therapeutic measures in irritable bladder and urge incontinence].

In an open study we report about the therapeutic influence of neural therapy in the periurethral region in patients with urgency. We treated 50 patients with neurohormonal urgency three times in 2-weeks interval by periurethral injections of 10 ml 0.25% Bupivacaine. Success was controlled in 46 patients with clinical and urodynamical methods. 10% of the least one time treated patients had the same complaints after therapy, 60% were improved by therapy and 30% were free of symptoms. We registered with urodynamic measurements a significant increase of the bladder volume up to the first sensation to void and a significant reduction of the bladder compliance. In a second randomized study the influence of a single acute maximum functional electrostimulation (AMFES) by vaginal electrode was tested. 10 patients with anamnestic urge incontinence in each case with uninhibited detrusor contractions and 10 patients without detrusor contractions was treated. The subjective statements yielded in urge incontinence without detrusor contractions a higher percentage of improvement than in motoric urge incontinence. The urodynamic diagnostic evaluation showed a relation between the unchanged objective conditions and the symptoms of complaint four weeks after treatment in patients with motoric urge incontinence. We recommend the use both of the neural therapy and functional electrostimulation as additional methods besides the dominant medicamentous treatment of the urgency and the urge incontinence.

Autonomic Nerve Block↗
PubMed2003

Limitations of current medical therapies for the treatment of heart failure.

The medical treatment of heart failure has evolved over the past 40 years, from the primary use of diuretics and digitalis in the 1960s to the use of inotropic agents and vasodilators in the 1970s. More recently, the focus has been on the neurohormonal system, specifically the renin-angiotensin-aldosterone system and the sympathetic nervous system. Drugs that inhibit or block these systems (eg, angiotensin-converting enzyme inhibitors and beta-blocking drugs) are the primary agents recommended in recent heart failure guidelines. However, the actual percent reduction in mortality associated with the use of these agents has been relatively modest. This article will review the results and limitations of medical therapy for heart failure. Our understanding of the pathogenesis of heart failure may be incomplete, and alternative strategies, including mechanical devices, may play an increasing role in the treatment of heart failure in the future.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Medical therapy of acute myocardial infarction: Part II. The role of adjunctive medical therapy.

The second part of this review summarizes the role of other classes of pharmacological therapy in treatment of acute myocardial infarction (MI). The goals of pharmacological therapy are to alleviate symptoms, to stabilize hemodynamic status, and to prevent arrhythmias. These agents have been utilized primarily because of their ability to limit infarct size. Other beneficial properties may include their effects on neurohormonal activation, hemodynamics, and arrhythmias. In an individual patient, age, associated medical conditions, and hemodynamic status are important considerations in choosing a specific class of drug therapy. The beta-adrenergic blocking agents have modest effects on mortality, and they are useful when used alone and in combination with thrombolytic agents. Calcium antagonists have a limited role in acute MI. Diltiazem reduces the incidence of reinfarction in patients with non-Q MI. Oral nitrate therapy has not been shown to reduce mortality. Data from recent trials suggest that prophylactic administration of antiarrhthymic therapy is also not useful in acute MI. The role of angiotensin-converting enzyme inhibitors when administered in the acute phase of MI needs to be evaluated further. These agents are safe and well tolerated, and they offer greatest benefit when given in patients with left ventricular dysfunction.

Acute Disease↗
PubMed2005

Rationale for the use of angiotensin II receptor blockers in patients with left ventricular dysfunction (part I of II).

Almost 5 million individuals in the United States are diagnosed with chronic heart failure (HF), and the prevalence is increasing. Angiotensin-converting enzyme (ACE) inhibitors and beta blockers, neurohormonal antagonists that block the renin-angiotensin system (RAS) and the sympathetic nervous system, respectively, have been shown in clinical trials to reduce morbidity and mortality in patients with HF, and these therapies are now integral components of standard HF treatment. Yet, morbidity and mortality rates in HF remain unacceptably high, and the limitations of current standard therapies are becoming increasingly apparent. About 10% of patients with HF are unable to tolerate ACE inhibitors, often because of cough. In addition, ACE inhibition may not completely block the RAS because angiotensin II, the main end product of the RAS, can be generated via non-ACE enzymatic pathways. Angiotensin II receptor blockers (ARBs) may exert more complete RAS blockade than ACE inhibitors by interfering with the binding of angiotensin II at the receptor level, regardless of the enzymatic pathway of production. They are also better tolerated than ACE inhibitors and have been shown to improve symptoms and function in clinical trials in patients with HF. These factors provide a strong rationale for the study of the clinical effects of ARBs in patients with HF.

Aged↗
PubMed1993

Neurohormonal response to ventricular failure: pharmacologic management.

Ventricular failure is accompanied by a series of neurohormonal responses that result in vasoconstriction. Vasoconstriction develops and is mediated by norepinephrine, angiotensin II, and vasopressin. Vasoconstriction maintains blood pressure but contributes to deterioration in ventricular function. Baroreceptor dysfunction contributes to the syndrome by failing to ameliorate the sympathetic overstimulation. Drug therapy has historically included positive inotropes until recent data suggested that these drugs contributed to worsened survival. The role of digitalis glycosides in patients with ventricular failure who are in normal sinus rhythm remains a subject of scrutiny. Thus far, no long-term oral positive inotrope has replaced digoxin. Vasodilator therapy and interference with the neurohormonal response have become the major approaches to pharmacologic management of ventricular failure. Angiotensin-converting enzyme inhibitors have shown convincingly that they improve survival, slow the course of disease progression, and block the neurohormonal response to ventricular failure. New treatments for ventricular failure must be directed at long-term gain rather than short-term hemodynamic results.

Angiotensin II↗