Significant Variation In Clinical Practice Research Articles

Child-to-adult transition: a survey of current practices within the European Reference Network for Rare Neurological Diseases (ERN-RND).

Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.

Diagnosis of Nocturnal Hypoventilation in Pediatric Neuromuscular Disorders: A Survey of Clinical Practice in Australia and New Zealand

Objectives: Nocturnal hypoventilation is a complication of neuromuscular disorders. There are various recommendations for measuring pCO<sub>2</sub> during polysomnography and numerous national and international definitions of hypoventilation that could contribute to significant variations in clinical practice. We therefore aimed to determine clinical practices implemented by Australasian pediatric sleep physicians.Methods: Pediatric sleep physicians completed an electronic survey for information regarding pCO<sub>2</sub> measurements and definitions of hypoventilation that are followed for children with neuromuscular disorders.Results: It was found that transcutaneous measurement of pCO<sub>2</sub> was performed in all centers, with 25% of the centers simultaneously performing capnography. Twelve definitions of hypoventilation were used, including published definitions from the American Academy of Sleep Medicine (AASM) manual and recommendations of the pediatric Australasian Sleep Association/Australasian Sleep Technologists Association. The most commonly used definition of hypoventilation (9/17, 53%) was the 2012 pediatric AASM definition (pCO<sub>2</sub> >50 mmHg for >25% of the total sleep time). There was a discrepancy between centers and individuals within the same center when defining hypoventilation. Answers stating the use of the Australasian definitions (rise in pCO<sub>2</sub> ≥10 mmHg from wake to sleep, average rise in pCO<sub>2</sub> ≥3 mmHg from non rapid eye movement to rapid eye movement sleep) were more frequent when asked specifically via a checkbox (yes/no) compared to free text.Conclusions: These results confirm the heterogeneity and lack of standardization of clinical practice within Australasia when measuring pCO<sub>2</sub> during polysomnography and defining hypoventilation. The Australasian definitions were not used as frequently as anticipated.

P137 Diagnosis of nocturnal hypoventilation in children with neuromuscular disorders by polysomnography – a survey of clinical practice in Australia and New Zealand

Abstract Background Diagnosis of nocturnal hypoventilation requires measurement of pCO2 during sleep, which can occur via exhaled gas (capnography) or transcutaneous methods. Different national and international definitions of hypoventilation exist, which may contribute to significant variation in clinical practice. Methods An electronic survey was completed by pediatric sleep physicians in Australia and New Zealand to determine how pCO2 was measured during polysomnography, what pCO2 data was available to reporting physicians/included in the report and which definitions of hypoventilation physicians use. Results More than two thirds (70%) of physicians indicated that in their centre pCO2 was collected via transcutaneous measurement only and 30% by both transcutaneous and end-tidal measurement. Twelve definitions of hypoventilation were used, including published definitions from the American Academy of Sleep Medicine manual and the pediatric Australasian Sleep Association/Australasian Sleep Technologists Association recommendations. The most commonly used definition was an increase in pCO2 >50mmHg for >25% total sleep time. The percentage of total sleep time with pCO2 >50mmHg was routinely included in the report and/or easily available in the raw data for 70% of physicians. Discussion There was significant variation and lack of standardisation within Australia and New Zealand when measuring and reporting pCO2 during polysomnography as well as definitions of hypoventilation used by pediatric sleep physicians. The Australasian Sleep Association/Australasian Sleep Technologists Association recommendations were not frequently used, possibly due to relevant information not being available to reporting physicians, recommendations being irrelevant and/or outdated and excessive cognitive load associated with remembering multiple definitions.

Variation in paediatric 24-h ambulatory blood pressure monitoring interpretation by Canadian and UK physicians.

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is widely accepted as a more accurate method for measurement of blood pressure (BP) compared to a single office-based measurement of BP. However, it is unclear how physicians interpret ABPM and make management decisions. This study's goal is to investigate variation in ABPM interpretation among paediatric nephrologists (Canada and UK) and paediatric cardiologists (Canada only) via an online survey. The survey content included baseline demographics, questions on the use and indications for ABPM, interpretation of results, and subsequent management decisions in various clinical scenarios. The survey was sent to 196 Canadian physicians, with 69 (35.2%) total responses. Thirty-five UK clinicians also completed the survey. Most respondents were >44 years old, were in practice for at least 11 years, and were university-based. There were substantial differences among clinicians in ABPM interpretation for isolated systolic, diastolic, and night-time hypertension. For example, only 53.1% of physicians would initiate or modify treatment in those with diastolic HTN in CKD. Further, even for the same abnormal ABPM parameter, the decision to start or alter treatment was influenced by the underlying medical condition. There is significant variation in clinical practice among physicians for interpretation and management of hypertension when using ABPM. Differences in guidelines among various jurisdictions, as well as knowledge gaps in the research on which guidelines are based, create ambiguity regarding ABPM interpretation and management decisions. A more protocolized approach and further insight into the reasoning behind the variation in physicians' interpretation may help to standardise practice.

Large Variation in Heart Transplant Selection Practices During the COVID-19 Pandemic

PurposeA growing proportion of transplant donors and recipients have a history of COVID infection. Transplant societies issued guidelines to support decisions regarding donor selection and recipient activation after COVID infection, but outcome data are still limited. This study sought to characterize heterogeneity in current clinical practice and opinions regarding cardiac donation after recipient or donor COVID infection.MethodsAn online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and October 18, 2021.Results204 healthcare professionals from diverse geographic regions (North and South America, Europe, Middle East, Asia and Australia) completed the survey, including 143 (70%) transplant cardiologists, 42 (21%) cardiac surgeons and 19 (9%) other heart transplant clinicians. 80% of clinicians felt COVID vaccine should be mandatory before transplant. There was significant variation in clinical practice for donor acceptance and recipient management, including several scenarios directly addressed by society guidelines - see Figure 1 for a sample of responses.ConclusionThere is significant variation in the clinical approach to common scenarios following donor or recipient COVID infection. This reflects continued uncertainty with post-transplant outcomes impacted by pre-transplant COVID infection. Granular outcome data are needed to better inform clinical decisions.

EP.FRI.537 Post-operative antibiotics for cutaneous abscess after incision and drainage: Variations in Clinical Practice or lack of guidelines

Abstract Aims Acute cutaneous abscess is a common surgical condition which mostly require incision and drainage. Despite this, there is no standardised national or international guidance on the post-operative antibiotics prescription. Traditionally, antibiotics are not indicated unless complications and/or risk factors such as immunocompromisation, diabetes or cellulitis exist. We aimed to study the local practice of the post-operative antibiotics prescription for cutaneous abscesses in a University teaching hospital in London. Methods A retrospective data collection of emergency general surgical admissions for a period of six months from July to December 2020 was carried out. All patients with superficial skin abscess were included in this analysis. Scrotal, breast and limb abscesses were excluded. Patients’ demographics, Co-morbidities, local and systemic complications were studied. Results A total of 149 patients presented during this period. Mean age was 40 (54% were male). Most common site of abscess was perianal (24%), followed by pilonidal, axilla, back, gluteal, neck, abdominal wall and groin. At total of 108 (72.5%) were managed surgically with incision and drainage, 70 (65%) got antibiotics and only 23 (33%) had indications for it (i.e. diabetic, immunocompromised, sepsis, cellulitis, MRSA carriage) = (χ2[1] =22.03, p<.0001). Co-amoxiclav was the most common post-operative empirical antibiotic prescribed in 61% of the patients. Conclusions This study has identified significant variation in clinical practice regarding post-operative antibiotic usage in superficial abscesses. Further research is required in cooperation with microbiologists to develop standardised evidence-based treatment protocol for management of such common surgical condition.

Monitoring, Delivery and Outcome in Early Onset Fetal Growth Restriction

Early fetal growth restriction (FGR) remains a challenging entity associated with an increased risk of perinatal morbidity and mortality as well as maternal complications. Significant variations in clinical practice have historically characterized the management of early FGR fetuses. Nevertheless, insights into diagnosis and management options have more recently emerged. The aim of this review is to summarize the available evidence on monitoring, delivery and outcome in early-onset FGR.

Management of recurrent implantation failure: British Fertility Society policy and practice guideline

Recurrent implantation failure (RIF) is defined as the absence of a positive pregnancy test after three consecutive transfers of good quality embryos. There remains significant variation in clinical practice in the management of RIF. This British Fertility Society (BFS) Policy and Practice guideline analyses the evidence for investigations and therapies that are employed in RIF and provides recommendations for clinical practice and for further research. Evidence for investigations of sperm and egg quality, uterine and adnexal factors, immunological factors and thrombophilia, endocrine conditions and genetic factors and for associated therapies have been evaluated. This guideline has been devised to assist reproductive medicine specialists and patients in making shared decisions concerning management of RIF. Finally, suggestions for research towards improving understanding and management of RIF have also been provided.

The Use of Coronectomy to Manage Symptomatic Mandibular Third Molars: Techniques, Pitfalls and Suggested Guidelines

Coronectomy is a valuable technique in the management of symptomatic mandibular third molars at high risk of inferior alveolar nerve injury. When applied appropriately, the technique may reduce the incidence of inferior alveolar nerve injury in comparison to full surgical removal. Currently, no definitive guidelines exist on when to opt for coronectomy versus full surgical removal, and therefore significant variation in clinical practice exists. This article summarizes the surgical stages involved in the coronectomy procedure, reviews the indications and hazards of the technique, and finally provides suggested guidelines to assist the practitioner in the decision-making process of when to opt for coronectomy versus full surgical removal in the management of symptomatic mandibular third molars. CPD/Clinical Relevance: To review the coronectomy technique and highlight potential hazards with inappropriate application of the technique.

An Evaluation of the Use of Aggressive Fluid Resuscitation in the Early Treatment of Sepsis Patients.

IntroductionFluid resuscitation is a critical aspect of the sepsis protocol with the usual initial dose being 30 mL per kilogram. Although this dose is well accepted in patients with normal cardiac function, there is some significant variation in clinical practice concerning the optimal fluid resuscitation in septic patients with underlying congestive heart failure (CHF). Many different approaches have been tried to best treat these patients by using lesser volumes of fluid. The purpose of this retrospective study is to attempt to better define optimal fluid resuscitation in congestive heart failure patients and whether standard fluid resuscitation exacerbates CHF in these cases.MethodsThis was a retrospective study involving patients admitted to the Emergency Department (ED) during the time period of September of 2016 through March of 2019 with a primary diagnosis of sepsis and pre-existing CHF. Data collected from the data warehouse and patient charts included demographics, total amount of fluid received in the ED and outcome data. Evidence of fluid overload (chest X-ray [CXR] evidence, rising B-type natriuretic peptide [BNP], or use of diuretics), was evaluated with respect to in-hospital mortality, white blood cell (WBC) count and comorbidities (chronic obstructive pulmonary disease [COPD], hypertension and coronary artery disease).ResultsThere were 422 patients included in the cohort. Of the 422, 113 (26.8%) patients showed evidence of fluid overload on CXR during hospital stay and received diuretics and therefore considered in the CHF exacerbation group. The patients that experienced CHF exacerbation were significantly older (mean ± SD, 70.9 ± 11.8 years versus 67.4 ± 15.1 years, p=0.014). Patients with exacerbation also received more fluid (median and interquartile range, 3.0, 2:5.5 L versus 2.0, 1:4.3 L, p=0.017). The receiver operating characteristic curve analysis for fluid to predict exacerbation resulted in an area under the curve of 0.59 with a 95% confidence interval (CI) of 0.52 to 0.65, p=0.012. The Youden Index was used to determine an optimal cutoff value of 2.6 L. The percentage of patients in the exacerbation group above the threshold was significantly higher (57.3%) than those without exacerbation (43.3%), p=0.019. Following multivariate analysis, age greater than 60 (odds ratio [OR]: 2.5; CI: 1.4-4.6, p=0.003) and fluid cutoff of 2.6 L (OR: 1.9; CI: 1.2-3.1, p=0.007) were both found to be independent predictors of CHF exacerbation. There was no significant difference in mortality based on the total fluid received in the ED.ConclusionThe findings of this study showed that septic patients with pre-existing CHF who received more than 2.6 L of fluid in the ED were 90% more likely to develop symptoms of CHF exacerbation with no evidence of lowering mortality compared to the group that received less than 2.6 L. Our data supports the practice of limiting total fluid resuscitation in CHF to 2.6 L and reconfirms the idea that fluid resuscitation for patients with CHF needs to be individualized.

Intrathecal catheter use after accidental dural puncture in obstetric patients: literature review and clinical management recommendations.

If an accidental dural puncture occurs, one option is to insert a catheter and use it as an intrathecal catheter. This avoids the need for a further injection and can rapidly provide labour analgesia and anaesthesia for caesarean section. However, there are no recommendations for managing intrathecal catheters and, therefore, significant variation in clinical practice exists. Mismanagement of the intrathecal catheter can lead to increased motor block, high spinal anaesthesia, drug error, hypotension and fetal bradycardia. Care must be taken with an intrathecal catheter to adhere to strict aseptic technique, meticulous labelling, cautious administration of medications and good communication with the patient and other staff. Every institution considering the use of intrathecal catheters should establish a protocol. For labour analgesia, we recommend the use of dilute local anaesthetic agents and opioids. For caesarean section anaesthesia, gradual titration to the level of the fourth thoracic dermatome, with full monitoring, in a facility equipped to manage complications, should be performed using local anaesthetics combined with lipophilic opioids and morphine or diamorphine. Although evidence of the presence and duration of intrathecal catheters on the development of post-dural puncture headache and need for epidural blood patch is limited, we suggest considering leaving the intrathecal catheter in for 24 hours to reduce the chance of developing a post-dural puncture headache while maintaining precautions to avoid drug error and cerebrospinal fluid leakage. Injection of sterile normal saline into the intrathecal catheter may reduce post-dural puncture headache. The level of evidence for these recommendations was low.

Pros and cons of hemi-thyroidectomy for low-risk differentiated thyroid cancer.

The debate regarding the surgical management of low-risk differentiated thyroid cancer (DTC) is ongoing. The recommended extent of surgery in DTC is based on an assessment of the predicted risk of recurrence and recent guidelines reflect an evolving philosophy of de-escalation of surgical management, informed by a growing understanding of the determinants of tumour biology and important prognostic factors. However, our current clinical and pathological risk stratification processes are imperfect and hence there is significant variation in clinical practice. Surgeons face the challenge of finding the balance between avoiding overtreatment, minimizing complications and providing adequate oncological management. This article discusses the nuances of the current management guidelines as well as the important considerations in preoperative decision making.

Infection prophylaxis patterns following pediatric autologous hematopoietic stem cell transplantation: A survey of Pediatric Transplant and Cell Therapy Consortium centers.

No standardized guidelines exist for infectious prophylaxis following pediatric auto-HSCT. We hypothesized significant variation in clinical practice. Thirty-three Pediatric Transplant and Cell Therapy Consortium centers completed a survey to assess institutional management. The majority utilize viral (91%) and fungal prophylaxis (94%), but duration varies. Bacterial prophylaxis during neutropenia is instituted by 42%. Our study demonstrates marked practice variability in infectious prophylaxis across centers. Additional research is needed to address patterns of infectious complications and to develop meaningful clinical practice guidelines for pediatric auto-HSCT.

Controversies in the surgical management of sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) represents a wide spectrum of tumours with differing biology, behaviour and natural history. The only current available curative treatment is surgery in the form of thyroidectomy with or without ipsilateral or bilateral neck dissection. There is a lack of consensus in the available published guidelines on the optimum extent of initial surgery, and there is significant variation in clinical practice. This review focuses on the most recently published evidence. Many patients with limited disease do not receive total thyroidectomy and central neck compartment dissection as recommended by international guidelines. Despite this, 5-year disease-specific survival is over 90% in those without distant metastases at presentation. Over 20% of patients may harbour occult lateral compartment nodal metastases, and baseline calcitonin alone (>1000 pg/ml) is not a good predictor of nodal metastasis. Although delayed lateral neck compartment dissection results in similar survival outcomes to prophylactic neck dissection for clinically node-negative patients, there is an underappreciated psychological effect of having biochemical evidence of persistent disease following limited surgery. No single currently available prognostic indicator is sufficient to predict disease behaviour and evidence of occult nodal metastases. In clinically ad radiologically node-negative patients, the extent of neck dissection at initial operation, therefore, needs to be planned and executed on an individual patient basis.

Gray areas and evidence gaps in the management of rectal cancer as revealed by the comparison of recommendations from national and international clinical guidelines.

74 Background: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. Methods: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e., identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e., substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence according to the Oxford CEBM Levels of Evidence guidelines by using the χ2 statistic test. Results: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 2/10 cases (20%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 4.4726, p = 0.034). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. Conclusions: Substantial variation exists across national and international clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.

National Variation in Radiation Oncology Procedures

Significant variation in clinical practice exists in the US healthcare system, particularly with regard to well-reimbursed procedures. Predictors of radiotherapy (RT) procedures and technologies, however, remain poorly characterized. We hypothesized that provider gender, practice rurality, practice region, and length of experience would predict for the use of specific RT procedures in the Medicare population. The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File (POSPUF), which includes all Healthcare Common Procedure Coding System (HCPCS) codes reimbursed by Medicare for individual physicians in 2016, was linked to the CMS Physician Compare database by National Provider Identifier (NPI). Entries that could not be linked or lacked our variables of interest were excluded. Covariates for multivariable regression analysis included provider gender (male vs female), practice rurality (metro vs non-metro), practice region (Midwest vs South vs West vs Northeast), and years since graduation. Treatment delivery HCPCS codes for 3D-conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic radiosurgery (SRS), stereotactic body RT (SBRT), low dose rate brachytherapy (LDR), and high dose rate brachytherapy (HDR) were evaluated as response variables. All fits were obtained via logistic regression. 1,802 physicians were available for analysis: 1,383 (76.7%) were male and 419 (23.3%) were female. 119 (6.6%) practiced in rural areas while 1683 (93.4%) practiced in metro areas. 378 (21.0%) providers practiced in the Midwest, 290 (16.1%) in the Northeast, 743 (41.2%) in the South, and 391 (21.7%) in the West. Mean time from medical school graduation was 26.56 years (SD 11.14). On multivariable regression analysis, male gender predicted for LDR use (OR 8.19, p<0.001), but not the use of other technologies, while metro practice predicted for greater utilization of HDR (OR 12.95, p=0.01). Use of 3DCRT was more likely in the South (OR 1.33, p<0.01) and the West (OR 1.38, p<0.01) than the Northeast whereas SRS was less common in the Midwest (OR 0.71, p<0.01), South (OR 0.49, p<0.001), and West (OR 0.43, p<0.001) relative to the Northeast. SBRT, on the other hand, was more commonly utilized in the Midwest (OR 2.63, p=0.03), South (OR 3.44, p<0.01), and West (OR 4.87, p<0.001) compared to the Northeast. HDR use was also greater in the Midwest (OR 1.97, p=0.02) and West (OR 1.87, p=0.03) compared to the Northeast. Longer practice experience was related to lower SBRT use (OR 0.98, p<0.001) and higher utilization of LDR (OR 1.02, p=0.02). Aside from LDR, gender does not influence procedure use, though adopting newer technology appears to be inversely related with experience. Substantial geographic variation in the use of specific RT technologies was identified. The degree to which this variation reflects effective care, preference-sensitive care, or supply-sensitive care warrants further investigation.

Quality indicators for Barrett’s endotherapy (QBET): UK consensus statements for patients undergoing endoscopic therapy for Barrett’s neoplasia

IntroductionEndoscopic therapy for the management of patients with Barrett’s oesophagus (BE) neoplasia has significantly developed in the past decade; however, significant variation in clinical practice exists. The aim of this...

Impact of Drain Placement and Duration on Outcomes After Pancreaticoduodenectomy: A National Surgical Quality Improvement Program Analysis

BackgroundThe decisions to routinely place a drain after pancreaticoduodenectomy and how long to leave the drain remain controversial due to conflicting evidence and significant variations in clinical practice. This study aims to address those questions by using a large national database and a rigorous analytical model. MethodsThe American College of Surgeons National Surgical Quality Improvement Program 2015-2016 Pancreatectomy Participant Use Data Files were used to identify patients who had undergone pancreaticoduodenectomy (n = 7583). Univariable and multivariable binomial regression analyses were performed to control for potential confounders and various preoperative risk factors. Cox regression with drain as a time-dependent covariate, conditional on having a drain placed, was used to examine the association between the drain remaining in place and morbidities. ResultsOf 7583 patients, drains were placed in 6666 (87.9%). Drain placement decreased the risk of developing serious morbidity (relative risk [RR] 0.73, 95% confidence interval [CI] 0.65-0.82), overall morbidity (RR 0.79, 95% CI 0.72-0.87), and organ space surgical site infection (RR 0.72, 95% CI 0.61-0.85). Drain placement did not change the risk of developing a clinically relevant postoperative pancreatic fistula (RR 0.96, 95% CI 0.78-1.19). However, for those with drains placed, length of drainage was independently associated with serious morbidity (hazard ratio [HR] 3.06, 95% CI 2.65-3.53), overall morbidity (HR 2.48, 95% CI 2.20-2.80), and organ space surgical site infection (HR 1.47, 95% CI 1.23-1.74). ConclusionsRoutine drain placement following pancreaticoduodenectomy may decrease postoperative complications, including serious morbidity, overall morbidity, and organ space surgical site infections; however, length of drainage was associated with increased risk of the previously-named complications. These results support the routine placement and early removal of intraoperative surgical drains in pancreaticoduodenectomy.

Controversies on the endoscopic and surgical management of pain in patients with chronic pancreatitis: pros and cons!

Pain is the dominating symptom of chronic pancreatitis (CP) causing impairment of quality of life, decreased activity, unemployment and major healthcare costs.1 Opinions differ on the best strategy to treat...

REGIONAL VARIATION IN CHRONIC INOTROPE INFUSION IN ADVANCED HEART FAILURE

Chronic inotrope infusion is utilized as a therapeutic or palliative strategy in chronic advanced heart failure for a variety of clinical goals. Due to the paucity of evidence available to guide usage, there is a significant variation in clinical practice. Their mechanism of action, specifically