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1.
BMC Cardiovasc Disord ; 24(1): 247, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38730379

ABSTRACT

BACKGROUND: Despite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking. METHODS: A survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4-5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest. RESULTS: Cardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07-3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18-4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01-3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48-4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine. CONCLUSIONS: Our results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.


Subject(s)
Cardiologists , Cardiovascular Agents , Guideline Adherence , Health Care Surveys , Heart Failure , Practice Guidelines as Topic , Practice Patterns, Physicians' , Stroke Volume , Ventricular Function, Left , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Heart Failure/diagnosis , Practice Patterns, Physicians'/standards , Stroke Volume/drug effects , Guideline Adherence/standards , Male , Female , Cardiovascular Agents/therapeutic use , Cardiovascular Agents/adverse effects , Ventricular Function, Left/drug effects , Middle Aged , Treatment Outcome , Clinical Decision-Making , Healthcare Disparities , Internal Medicine , General Practitioners , Aged , United States
4.
JAMA Cardiol ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630494

ABSTRACT

Importance: Although the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status. Objective: To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status. Design, Setting, and Participants: This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024. Interventions: Atrial shunt device or sham control. Main Outcome Measures: Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure. Results: The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, -5.65 mL; P <.001), left atrial (LA) minimal volume (mean difference, -2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P <.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P <.001) and right atrial (RA; mean difference, 9.71 mL; P <.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P <.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs -1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading. Conclusions and Relevance: In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03088033.

5.
J Card Fail ; 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38211934

ABSTRACT

OBJECTIVE: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. METHODS: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. RESULTS: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION: NCT04592445.

6.
Eur J Heart Fail ; 26(1): 177-189, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37989800

ABSTRACT

AIMS: Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. METHODS AND RESULTS: The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2 . As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e' were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. CONCLUSIONS: Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.


Subject(s)
Flavins , Heart Failure , Luciferases , Humans , Stroke Volume , Cardiac Catheterization , Ventricular Remodeling , Quality of Life , Heart Atria , Obesity/complications , Ventricular Function, Left
7.
J Am Geriatr Soc ; 71(11): 3367-3375, 2023 11.
Article in English | MEDLINE | ID: mdl-37706670

ABSTRACT

BACKGROUND: Malnutrition may be an important geriatric condition in adults with heart failure with preserved ejection fraction (HFpEF), but studies on its prevalence and associated clinical outcomes are limited. The aim of this study was to determine if malnutrition is associated with short-term morbidity and mortality in ambulatory patients with HFpEF. METHODS: We examined 231 patients with a clinical diagnosis of HFpEF seen at two dedicated academic HFpEF programs (Weill Cornell Medicine and Michigan Medicine) from June 2018 to April 2022. Malnutrition was defined by Mini-Nutritional Assessment Short Form (MNA-SF) scores ≤11. The primary endpoint was a 6-month composite of all-cause mortality and all-cause hospitalization. A Cox proportional-hazard models was used to examine the association between malnutrition and the primary endpoint, adjusting for race, prior hospitalization history, and the validated Meta-Analysis Global Group in Chronic (MAGGIC) heart failure prognostic risk score. RESULTS: The median age of the cohort was 73 years (interquartile range 64-81). The most common comorbid conditions included hypertension (prevalence 81%), atrial fibrillation (43%), and obesity (63%). The prevalence of malnutrition was 42% (n = 97), and MNA-SF scores did not significantly correlate with body mass index (R = -0.02, p = 0.71). At the 6-month follow-up, 62 patients (26.8%) were hospitalized and four patients died (1.7%). In a fully-adjusted analysis, malnutrition was independently associated with the composite outcome of all-cause mortality and all-cause hospitalization (HR 1.94 [95% CI: 1.17-3.20], p = 0.01). CONCLUSION: Despite a high prevalence of obesity, two out of five ambulatory adults with HFpEF are malnourished. Malnutrition was independently associated with adverse outcomes at 6 months. Future work is necessary to develop interventions that can address malnutrition.


Subject(s)
Heart Failure , Malnutrition , Aged , Humans , Heart Failure/complications , Heart Failure/epidemiology , Heart Failure/diagnosis , Hospitalization , Malnutrition/complications , Malnutrition/epidemiology , Obesity/complications , Prognosis , Stroke Volume , Ventricular Function, Left , Middle Aged , Aged, 80 and over
8.
JACC Adv ; 2(5)2023 Jul.
Article in English | MEDLINE | ID: mdl-37575202

ABSTRACT

We review a comprehensive risk assessment approach for percutaneous coronary interventions in older adults and highlight the relevance of geriatric syndromes within that broader perspective to optimize patient-centered outcomes in interventional cardiology practice. Reflecting the influence of geriatric principles in older adults undergoing percutaneous coronary interventions, we propose a "geriatric" heart team to incorporate the expertise of geriatric specialists in addition to the traditional heart team members, facilitate uptake of the geriatric risk assessment into the preprocedural risk assessment, and address ways to mitigate these geriatric risks. We also address goals of care in older adults, highlighting common priorities that can impact shared decision making among older patients, as well as frequently encountered pharmacotherapeutic considerations in the older adult population. Finally, we clarify gaps in current knowledge and describe crucial areas for future investigation.

9.
JACC Adv ; 2(4)2023 Jun.
Article in English | MEDLINE | ID: mdl-37584013

ABSTRACT

As the population ages, older adults represent an increasing proportion of patients referred to the cardiac catheterization laboratory. Older adults are the highest-risk group for morbidity and mortality, particularly after complex, high-risk percutaneous coronary interventions. Structured risk assessment plays a key role in differentiating patients who are likely to derive net benefit vs those who have disproportionate risks for harm. Conventional risk assessment tools from national cardiovascular societies typically rely on 3 pillars: 1) cardiovascular risk; 2) physiologic and hemodynamic risk; and 3) anatomic and procedural risks. We propose adding a fourth pillar: geriatric syndromes, as geriatric domains can supersede all other aspects of risk.

11.
Am J Cardiol ; 193: 70-74, 2023 04 15.
Article in English | MEDLINE | ID: mdl-36878055

ABSTRACT

ß-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for ß-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding ß-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for ß-blocker initiation, agreement regarding initiation and/or continuation of ß-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n = 231). Among respondents, 68.2% reported initiating ß-blockers in patients with HFpEF. The most common reason for initiating a ß-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a ß-blocker without an evidence-based indication. When a ß-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a ß-blocker when the physician felt that a ß-blocker was unnecessary was the concern about interfering with another physicians' treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing ß-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe ß-blockers in these scenarios.


Subject(s)
Cardiologists , Heart Failure , Humans , Heart Failure/drug therapy , Stroke Volume/physiology , Adrenergic beta-Antagonists/therapeutic use , Drug Prescriptions
12.
Obesity (Silver Spring) ; 31(5): 1347-1361, 2023 05.
Article in English | MEDLINE | ID: mdl-36988872

ABSTRACT

OBJECTIVE: The aims of this study were: 1) to assess relationships among insulin-mediated glucose uptake with standard clinical outcomes and deep-phenotyping measures (including fatty acid [FA] rate of appearance [FA Ra] into the systemic circulation); and 2) to examine the contribution of adipocyte size, fibrosis, and proteomic profile to FA Ra regulation. METHODS: A total of 66 adults with obesity (BMI = 34 [SD 3] kg/m2 ) were assessed for insulin sensitivity (hyperinsulinemic-euglycemic clamp), and stable isotope dilution methods quantified glucose, FA, and glycerol kinetics in vivo. Abdominal subcutaneous adipose tissue (aSAT) and skeletal muscle biopsies were collected, and magnetic resonance imaging quantified liver and visceral fat content. RESULTS: Insulin-mediated FA Ra suppression associated with insulin-mediated glucose uptake (r = 0.51; p < 0.01) and negatively correlated with liver (r = -0.36; p < 0.01) and visceral fat (r = -0.42; p < 0.01). aSAT proteomics from subcohorts of participants with low FA Ra suppression (n = 8) versus high FA Ra suppression (n = 8) demonstrated greater extracellular matrix collagen protein in low versus high FA Ra suppression. Skeletal muscle lipidomics (n = 18) revealed inverse correlations of FA Ra suppression with acyl-chain length of acylcarnitine (r = -0.42; p = 0.02) and triacylglycerol (r = -0.51; p < 0.01), in addition to insulin-mediated glucose uptake (acylcarnitine: r = -0.49; p < 0.01, triacylglycerol: r = -0.40; p < 0.01). CONCLUSIONS: Insulin's ability to suppress FA release from aSAT in obesity is related to enhanced insulin-mediated glucose uptake and metabolic health in peripheral tissues.


Subject(s)
Insulin Resistance , Insulin , Adult , Humans , Insulin/metabolism , Fatty Acids/metabolism , Proteomics , Obesity/complications , Adipose Tissue/metabolism , Insulin Resistance/physiology , Triglycerides/metabolism , Glucose/metabolism , Glucose Clamp Technique
13.
JACC Heart Fail ; 11(8 Pt 2): 1103-1117, 2023 08.
Article in English | MEDLINE | ID: mdl-36939661

ABSTRACT

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).


Subject(s)
Atrial Fibrillation , Heart Failure , Hypertension , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/therapy , Cardiac Catheterization , Heart Failure/complications , Heart Failure/therapy , Heart Failure/diagnosis , Stroke Volume/physiology , Ventricular Function, Left
14.
Eur J Heart Fail ; 25(6): 806-814, 2023 06.
Article in English | MEDLINE | ID: mdl-36847073

ABSTRACT

AIMS: Elevated left atrial (LA) pressure is a pathophysiologic hallmark of heart failure with preserved ejection fraction (HFpEF). Chronically elevated LA pressure leads to LA enlargement, which may impair LA function and increase pulmonary pressures. We sought to evaluate the relationship between LA volume and pulmonary arterial haemodynamics in patients with HFpEF. METHODS AND RESULTS: Data from 85 patients (aged 69 ± 8 years) who underwent exercise right heart catheterization and echocardiography were retrospectively analysed. All had symptoms of heart failure, left ventricular ejection fraction ≥50% and haemodynamic features of HFpEF. Patients were divided into LA volume index-based tertiles (≤34 ml/m2 , >34 to ≤45 ml/m2 , >45 ml/m2 ). A subgroup analysis was performed in patients with recorded LA global reservoir strain (n = 60), with reduced strain defined as ≤24%. Age, sex, body surface area and left ventricular ejection fraction were similar between volume groups. LA volume was associated with blunted increases in cardiac output with exercise (padjusted <0.001), higher resting mean pulmonary artery pressure (padjusted  = 0.003), with similar wedge pressure (padjusted  = 1). Pulmonary vascular resistance (PVR) increased with increasing LA volume (padjusted <0.001). Larger LA volumes featured reduced LA strain (padjusted <0.001), with reduced strain associated with reduced PVR-compliance time (0.34 [0.28-0.40] vs. 0.38 [0.33-0.43], p = 0.03). CONCLUSION: Increasing LA volume may be associated with more advanced pulmonary vascular disease in HFpEF, featuring higher PVR and pulmonary pressures. Reduced LA function, worse at increasing LA volumes, is associated with a disrupted PVR-compliance relationship, further augmenting impaired pulmonary haemodynamics.


Subject(s)
Atrial Fibrillation , Heart Failure , Vascular Diseases , Humans , Stroke Volume/physiology , Ventricular Function, Left , Retrospective Studies
15.
Future Cardiol ; 19(1): 7-17, 2023 01.
Article in English | MEDLINE | ID: mdl-36715498

ABSTRACT

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study and ATTR-ACT have a type of heart disease known as transthyretin amyloid cardiomyopathy (ATTR-CM for short), which causes heart failure and death. In ATTR-ACT, people took either a medicine called tafamidis or a placebo (a pill that looks like the study drug but does not contain any active ingredients) for up to 2½ years. So far, in the long-term extension study, people have continued taking tafamidis, or switched from taking a placebo to tafamidis, for another 2½ years. Researchers looked at how many people died in ATTR-ACT and the extension study. The long-term extension study is expected to end in 2027, so these are interim (not final) results. WHAT DID RESEARCHERS FIND OUT?: In the extension study of ATTR-ACT, the risk of dying was lower in people who took tafamidis continuously throughout ATTR-ACT and the extension study than in people who took placebo in ATTR-ACT and switched to tafamidis in the extension study. WHAT DO THE RESULTS MEAN?: Taking tafamidis increases how long people with ATTR-CM live. People with ATTR-CM who take tafamidis early and continuously are more likely to live longer than those who do not. These results highlight the importance of early detection and treatment in people with ATTR-CM. Clinical Trial Registration: NCT01994889 (ClinicalTrials.gov) Clinical Trial Registration: NCT02791230 (ClinicalTrials.gov).


Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Humans , Amyloid Neuropathies, Familial/drug therapy , Prealbumin/therapeutic use , Benzoxazoles/therapeutic use
16.
Cardiovasc Drugs Ther ; 37(2): 307-313, 2023 04.
Article in English | MEDLINE | ID: mdl-34792686

ABSTRACT

PURPOSE: Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19). Although our understanding of the pathogenesis of COVID-19 has rapidly evolved, much of the focus has been on the immune mechanisms underlying COVID-19. In addition to immune dysfunction, vascular injury is also associated with COVID-19 and is a major driver of clinical deterioration in SARS-CoV-2 infections. The glycocalyx (GAC), a sugar-based shell that surrounds all mammalian cells, is an important regulator of vascular and immune responses. In sepsis, vascular dysfunction contributes to acute respiratory distress syndrome (ARDS) by altering vessel integrity, promoting thrombosis, and accelerating inflammation, all of which are also present in COVID-19. Observational studies in sepsis have found an association between levels of circulating GAC degradation products with both organ dysfunction and mortality. Although vascular dysfunction is a hallmark of COVID-19, it remains unclear whether GAC disruption occurs in COVID-19 and if GAC disruption contributes to the clinical progression of COVID-19. METHODS: In this prospective cohort study, we measured the GAC components syndecan-1 (SDC1) and hyaluronan (Hyal) along with inflammatory cytokines in 12 hospitalized COVID-19 patients and 8 healthy controls (HC). RESULTS: In agreement with other studies, we found that inflammatory cytokines are elevated in hospitalized COVID-19 patients compared with HC [median (IQR), all units picograms per milliliter: IL-6 4.65 (3.32-9.16) vs 0.69 (0.55-0.89), p < 0.001; TNFα 4.49 (1.87-8.03) vs 0.04 (0.04-0.84), p < 0.001]. Additionally, we found that the GAC components SDC1 and Hyal are also elevated in COVID-19 patients [median (IQR), all units picograms per milliliter: SDC1: 247.37 (101.43-458.26) vs 84.8 (52.88-123.59), p = 0.036; Hyal: 26.41 (16.4-35.1) vs 3.01 (1.66-4.61), p < 0.001]. CONCLUSION: We propose that GAC markers offer insights into the pathobiology of COVID-19, potentially guide therapeutic approaches, and could aid in early risk stratification that is particularly beneficial in phasic diseases such as COVID-19.


Subject(s)
COVID-19 , Sepsis , Animals , Humans , SARS-CoV-2 , Prospective Studies , Glycocalyx , Cytokines , Mammals
17.
J Am Heart Assoc ; 11(23): e025730, 2022 12 06.
Article in English | MEDLINE | ID: mdl-36382963

ABSTRACT

Background Descriptions of do not attempt resuscitation (DNAR) orders in heart failure (HF) are limited. We describe use of DNAR orders in HF hospitalizations relative to other common conditions, focusing on race. Methods and Results This was a retrospective study of all adult hospitalizations for HF, acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD), and pneumonia from 2010 to 2016 using the California State Inpatient Dataset. Using a hierarchical multivariable logistic regression model with random effects for the hospital, we identified factors associated with DNAR orders for each condition. For racial variation, hospitals were divided into quintiles based on proportion of Black patients cared for. Our cohort comprised 399 816 HF, 190 802 AMI, 192 640 COPD, and 269 262 pneumonia hospitalizations. DNAR orders were most prevalent in HF (11.9%), followed by pneumonia (11.1%), COPD (7.9%), and AMI (7.1%). Prevalence of DNAR orders did not change from 2010 to 2016 for each condition. For all conditions, DNAR orders were more common in elderly people, women, and White people with significant site-level variation across 472 hospitals. For HF and COPD, hospitalizations at sites that cared for a higher proportion of Black patients were less likely associated with DNAR orders. For AMI and pneumonia, conditions such as dementia and malignancy were strongly associated with DNAR orders. Conclusions DNAR orders were present in 12% of HF hospitalizations, similar to pneumonia but higher than AMI and COPD. For HF, we noted significant variability across sites when stratified by proportion of Black patients cared for, suggesting geographic and racial differences in end-of-life care.


Subject(s)
Heart Failure , Myocardial Infarction , Pneumonia , Pulmonary Disease, Chronic Obstructive , Humans , Female , Aged , Retrospective Studies , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/therapy , Myocardial Infarction/epidemiology , Myocardial Infarction/therapy , Pneumonia/epidemiology , Pneumonia/therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy
18.
Drugs Aging ; 39(11): 851-861, 2022 11.
Article in English | MEDLINE | ID: mdl-36227408

ABSTRACT

Medical management of heart failure (HF) has evolved and has achieved significant survival benefits, resulting in highly complex medication regimens. Complex medication regimens create challenges for older adults, including nonadherence and increased adverse drug events, especially associated with cognitive impairment, physical limitations, or lack of social support. However, the association between medication complexity and patients' health outcomes among older adults with HF is unclear. The purpose of this review is to address how the complexity of HF medications has been assessed in the literature and what clinical outcomes are associated with medication regimen complexity in HF. Further, we aimed to explore how older adults were represented in those studies. The Medication Regimen Complexity Index was the most commonly used tool for assessment of medication regimen complexity. Rehospitalization was most frequently assessed as the clinical outcome, and other studies used medication adherence, quality of life, healthcare utilization, healthcare cost, or side effect. However, the studies showed inconsistent results in the association between the medication regimen complexity and clinical outcomes. We also identified an extremely small number of studies that focused on older adults. Notably, current medication regimen complexity tools did not consider a complicated clinical condition of an older adult with multimorbidity, therapeutic competition, drug interactions, or altered tolerance to the usual dose strength of the medications. Furthermore, the outcomes that studies assessed were rarely comprehensive or patient centered. More studies are required to fill the knowledge gap identifying more comprehensive and accurate medication regimen complexity tools and more patient-centered outcome assessment.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Heart Failure , Humans , Aged , Quality of Life , Medication Adherence/psychology , Heart Failure/drug therapy
19.
Cardiol Clin ; 40(4): 397-413, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36210127

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is common and increasing in prevalence. Despite this, HFpEF is challenging to diagnose due in part to its shared clinical features with other comorbid conditions. HFpEF is now understood as a systemic syndrome, often driven by pro-inflammatory comorbidities, rather than solely a cardiac disease. This review summarizes the epidemiology, diagnostic criteria, and pathophysiology of HFpEF and proposes a clinical approach for patients suspected of having or diagnosed with HFpEF.


Subject(s)
Heart Failure , Comorbidity , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans , Prevalence , Stroke Volume/physiology , Ventricular Function, Left
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