Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF.

State-Level Social Vulnerability Index and Healthcare Access: The Behavioral Risk Factor Surveillance System Survey.

INTRODUCTION: Access to health care is affected by social determinants of health. The social vulnerability index encompasses multiple social determinants of health simultaneously and may therefore be associated with healthcare access. METHODS: Cross-sectional data were used from the 2016‒2019 Behavioral Risk Factor Surveillance System, a nationally representative U.S. telephone-based survey of adults aged ≥18 years. State-level social vulnerability index was derived using county-level social vulnerability index estimates from the Centers for Disease Control and Prevention Agency for Toxic Substances and Disease Registry. Analyses were performed in October 2021. Social vulnerability index was ranked according to percentiles, which were divided into tertiles: Tertile 1 (0.10-0.32), Tertile 2 (0.33-0.53), and Tertile 3 (0.54-0.90). RESULTS: In multivariable-adjusted models comparing U.S. states in Tertile 3 with those in Tertile 1 of social vulnerability index, there was a higher prevalence of absence of healthcare coverage (OR=1.39 [95% CI=1.22, 1.58]), absence of primary care provider (OR=1.34 [95% CI=1.22, 1.48]), >1-year duration since last routine checkup (OR=1.18 [95% CI=1.10, 1.27]), inability to see a doctor because of cost (OR=1.38 [95% CI=1.23, 1.54]), and the composite variable of any difficulty in accessing healthcare (OR=1.15 [95% CI=1.08, 1.22]). CONCLUSIONS: State-level social vulnerability is associated with several measures related to healthcare access. These results can help to identify targeted interventions to improve access to health care in U.S. states with high social vulnerability index burden.

Implementing a telemedicine curriculum for internal medicine residents during a pandemic: the Cleveland Clinic experience.

Telemedicine training was not a substantial element of most residency programmes prior to the COVID-19 pandemic. Social distancing measures changed this. The Cleveland Clinic Internal Medicine Residency Programme (IMRP) is one of the largest programmes in the USA, which made the task of implementing a telemedicine curriculum more complex. Here we describe our experience implementing an effective, expedited telemedicine curriculum for our ambulatory resident clinics. This study was started in April 2020 when we implemented a resident-led curriculum and training programme for providing ambulatory telemedicine care. The curriculum was finalised in less than 5 weeks. It entailed introducing a formal training programme for residents, creating a resource guide for different video communication tools and training preceptors to safely supervise care in this new paradigm. Residents were surveyed before the curriculum to assess prior experience with telemedicine, and then afterward to assess the curriculum's effectiveness. We also created a mini-CEX assessment for residents to solicit feedback on their performance during virtual appointments. Over 2000 virtual visits were performed by residents in a span of 10 weeks. Of 148 residents, 38% responded to the pre-participation survey. A majority had no prior telemedicine experience and expressed only slight comfort with the modality. Through collaboration with experienced residents and faculty, we expeditiously deployed an enhancement to our ambulatory care curriculum to teach residents how to provide virtual care and help faculty with supervision. We share our insights on this experience for other residency programmes to use.

A pulmonary embolism response team (PERT) approach: initial experience from the Cleveland Clinic.

Management of intermediate and high risk acute pulmonary embolism (PE) is challenging. The role of multidisciplinary teams for the care of these patients is emerging. Herein, we report our experience with a pulmonary embolism response team (PERT). We conducted a retrospective chart review on all patients admitted to the Cleveland Clinic main campus who required activation of the (PERT) from October 1, 2014 to September 1, 2016. We extracted data pertaining to clinical presentation, bleeding complications, and pre- and post-discharge imaging. Patients were classified as low, intermediate or high risk PE. Descriptive and continuous variables were collected and analyzed. There were 134 PERT activations. PE was confirmed by CT-PA in 118 patients. Fifteen (13%) patients were classified as low risk, 80 (68%) intermediate risk PE and 23 (19%) high risk PE. Fourteen (12%) patients were treated with catheter directed rtPA, 6 (5%) received full dose (100 mg rtPA), 16 (13%) received systemic half-dose (50 mg rtPA), 6 (5%) underwent a surgical embolectomy and 4 (3%) underwent mechanical thrombectomy. 65 (55%) patients received anticoagulation only, and 8 (7%) patients were managed conservatively without any anticoagulation or advanced therapy. 11 (9%) patients died while during the hospitalization. Fourteen patients had major bleeding events. There were no bleeding events among patients who received systemic low dose or full dose rtPA. A multidisciplinary approach to cases of intermediate risk and high risk PE can be implemented successfully. We saw a relatively low rate of bleeding events with use of rtPA.

Left atrial volumes and associated stroke subtypes.

BACKGROUND: Cardio embolism and cerebrovascular atherosclerosis are two major mechanisms of stroke. Studies investigating associations between advanced echocardiographic parameters and stroke mechanisms are limited. METHODS: This study is a standardized review of 633 patients admitted to the stroke service of a tertiary care hospital following a standardized stroke investigation and management pathway. Stroke subtypes were characterized using the Causative Classification System, using the hospitals online radiologic archival system with CCS certified stroke investigators. Patients with two mechanisms were excluded. RESULTS: Patients with cardioembolic stroke had a higher proportion of atrial fibrillation (p < 0.001), acute myocardial infarction (p < 0.001) and ischemic heart disease (p < 0.001). On electrocardiogram (ECG) and transthoracic Echo (TTE), patients with cardioembolic stroke had a greater atrial fibrillation (p < .00), left ventricular thrombus (p < .00), left ventricular ejection fraction <30% (p < .00) and global hypokinesia (p < .00) Patients with cardioembolic stroke had higher mean left atrial volume indices (LAVi) (p < 0.001), mean left ventricular mass indices (LVMi) (p < 0.05) and mean left atrial diameters (LAD) (p < 0.05). At LAVi of 29-33 ml/m2, the risk of atherothrombotic stroke increased. The risk of cardioembolic stroke increased with LAVi of 34 ml/m2 and above. CONCLUSION: Left atrial volume indices may be linked to specific stroke phenotype. At mild increases in left atrial dimensions, the risks of atherosclerotic stroke are high, and probably reflect hypertension as the unifying mechanism. Further increases in left atrial dimensions shifts the risk towards cardioembolic stroke.