sacubitril and Cardiomyopathies

Sacubitril/valsartan is an angiotensin receptor/neprilysin inhibitor that the Food and Drug Administration has indicated to reduce the risk of cardiovascular hospitalization and death in patients with left ventricular ejection fraction below normal and with no specified ejection-fraction cut-off. However, clinically significant patient groups were excluded or minimally represented in sacubitril/valsartan's pivotal clinical trials. Clinicians often encounter scenarios in which a sacubitril/valsartan off-label use may be beneficial, but limited resources are available to evaluate the efficacy and safety in these patients. This state-of-the-art review describes contemporary literature for sacubitril/valsartan Food and Drug Administration off-label indications to help clinicians assess its appropriateness in these selected, clinically important groups of patients: those with acute decompensated heart failure, acute coronary syndrome, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, adult congenital heart disease, cardiomyopathy in dialysis patients, right ventricular failure, or durable left ventricular assist device.

Topics: Adult; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiomyopathies; Drug Combinations; Heart Defects, Congenital; Heart Failure; Humans; Neprilysin; Off-Label Use; Stroke Volume; Tetrazoles; Valsartan; Ventricular Function, Left

In the year 2021, the universal definition and classification of heart failure (HF) was published that defines HF as a clinical syndrome with symptoms and/or signs caused by a cardiac abnormality and corroborated by elevated natriuretic peptide levels or objective evidence of cardiogenic congestion. This definition and the classification of HF with reduced ejection fraction (HFrEF), mildly reduced, and HF with preserved ejection fraction (HFpEF) is consistent with the 2021 ESC Guidelines on HF. Among several other new recommendations, these guidelines give a Class I indication for the use of the sodium-glucose co-transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin in HFrEF patients. As the first evidence-based treatment for HFpEF, in the EMPEROR-Preserved trial, empagliflozin reduced the composite endpoint of cardiovascular death and HF hospitalizations. Several reports in 2021 have provided novel and detailed analyses of device and medical therapy in HF, especially regarding sacubitril/valsartan, SGLT2 inhibitors, mineralocorticoid receptor antagonists, ferric carboxymaltose, soluble guanylate cyclase activators, and cardiac myosin activators. In patients hospitalized with COVID-19, acute HF and myocardial injury is quite frequent, whereas myocarditis and long-term damage to the heart are rather uncommon.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiomyopathies; COVID-19; Heart Failure; Humans; SARS-CoV-2; Stroke Volume

Cancer patients are at an increased risk of cardiovascular events. Both old-generation cytostatics/cytotoxics and new-generation "targeted" drugs can in fact damage cardiomyocytes, endothelial cells of veins and arteries, specialized cells of the conduction system, pericardium, and valves. A new discipline, cardio-oncology, has therefore developed with the aim of protecting cancer patients from cardiovascular events, while also providing them with the best possible oncologic treatment. Anthracyclines have long been known to elicit cardiotoxicity that, depending on treatment- or patient-related factors, may progress with a variable velocity toward cardiomyopathy and systolic heart failure. However, early compromise of diastolic function may precede systolic dysfunction, and a progression of early diastolic dysfunction to diastolic rather than systolic heart failure has been documented in long-term cancer survivors. This chapter first describes general notions about hypertension in the cancer patient and then moves on reviewing the pathophysiology and clinical trajectories of diastolic dysfunction, and the molecular mechanisms of anthracycline-induced diastolic dysfunction. Diastolic dysfunction can in fact be caused and/or aggravated by hypertension. Pharmacologic foundations and therapeutic opportunities to prevent or treat diastolic dysfunction before it progresses toward heart failure are also reviewed, with a special emphasis on the mechanisms of action of drugs that raised hopes to treat diastolic dysfunction in the general population (sacubitril/valsartan, guanylyl cyclase activators, phosphodiesterase inhibitors, ranolazine, inhibitors of type-2 sodium-glucose-inked transporter). Cardio-oncologists will be confronted with the risk:benefit ratio of using these drugs in the cancer patient.

Topics: Aminobutyrates; Anthracyclines; Antineoplastic Agents; Biphenyl Compounds; Cardiomyopathies; Endothelial Cells; Heart Failure, Systolic; Humans; Hypertension; Neoplasms

Arrhythmogenic right ventricular (RV) cardiomyopathy is an autosomal dominant inherited cardiomyopathy that is characterized by an increased risk of ventricular arrhythmias, sudden cardiac death and, less commonly, heart failure. The authors present the case of a 36-year-old woman with familial lamin cardiomyopathy with positive. The authors present the case of a 36-year-old woman who was found to have arrhythmogenic right ventricular cardiomyopathy, a rare inherited cardiomyopathy. This condition is caused by various mutations that lead to cardiac muscle cells being replaced with fibrofatty tissue and manifests as heart arrhythmias, sudden cardiac death or heart failure. The patient presented with symptoms of right heart failure. Imaging found a new reduction in right ventricular function, confirming the diagnosis of right heart failure. The patient was treated initially with diuretics. However, her symptoms persisted despite treatment and sacubitril–valsartan was started, after which she symptomatically improved. Repeat imaging showed improvement in right ventricular function with sacubitril–valsartan therapy.

Topics: Adult; Aminobutyrates; Arrhythmogenic Right Ventricular Dysplasia; Biphenyl Compounds; Cardiomyopathies; Contrast Media; Diuretics; Drug Combinations; Female; Gadolinium; Heart Failure; Humans; Valsartan

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiomyopathies; Catecholamines; Drug Combinations; Heart Failure; Humans; Paraganglioma; Stroke Volume; Tetrazoles; Valsartan

Although sacubitril/valsartan (Sac/Val) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF), gaps in care continue to exist for those with newer onset HFrEF vs those with longer durations of disease.. We categorized 794 persons with HFrEF (EF of ≤40%) according to a HF duration of less than 12 months, 12-24 months, 24-60 months, and more than> 60 months. After the initiation of Sac/Val, concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were measured, and Kansas City Cardiomyopathy Questionnaire 23 scores were obtained serially from baseline to 12 months. The left ventricular ejection fraction was measured by echocardiography. Significant decreases in the concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were observed regardless of HF duration (P < .001). Comparable gains in Kansas City Cardiomyopathy Questionnaire 23 scores were achieved in all HF duration categories. Moreover, consistent reverse cardiac remodeling in all HF duration categories occurred, with the absolute left ventricular ejection fraction improvement by 12 months across HF duration groups of 12.2%, 6.9%, 8.5%, and 8.6% for HF duration of less than 12 months, 12-24 months, 24-60 months, and more than 60 months, respectively.. The initiation of Sac/Val decreases prognostic biomarkers, improves health status, and reverses cardiac remodeling processes, regardless of HF duration.. We categorized 794 persons with heart failure owing to a low ejection fraction according to disease duration into 4 groups: less than 12 months, 12-24 months, 24-60 months, and more than 60 months. After the initiation of sacubitril/valsartan (Entresto), we found that regardless of the duration of heart failure significant improvements occurred in cardiac biomarkers, patients felt better with improved health status and on testing with cardiac ultrasound examination, improvement in heart size, and function occurred. These results suggest that, regardless of heart failure duration, patients with a reduced ejection fraction would benefit from use of sacubitril/valsartan for their care.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Cardiomyopathies; Drug Combinations; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Stroke Volume; Tetrazoles; Troponin T; Valsartan; Ventricular Function, Left; Ventricular Remodeling