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1.
Neuropsychiatr Dis Treat ; 20: 439-447, 2024.
Article in English | MEDLINE | ID: mdl-38439945

ABSTRACT

Purpose: This study aimed to validate a proposed association model previously published to determine the clinical relevance of pre-operative determinants in the development of PND after Cesarean delivery (CD). Patients and Methods: Parturients undergoing elective CD under neuraxial anesthesia were recruited for a prospective cohort study between Oct 2021 and Oct 2022 at KK Women's and Children's Hospital, Singapore. Predelivery pain, psychological and mechanical temporal summation, and demographic data were recorded. A follow-up survey was conducted at 6 to 10 weeks after CD. The primary outcome was the incidence of PND, defined as an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10. Results: A total of 180 patients were recruited for validation. PND 6 to 10 weeks post-delivery occurred in 18.9% of recruited parturients. Multivariate regression analyses showed that higher pre-operative CSI scores (p=0.0156), higher anxiety levels about upcoming surgery (p=0.0429), increased pre-operative pain scores on movement (p=0.0110), and higher pre-operative HADS subscale scores on anxiety (p=0.0041) were independently associated with the development of PND weeks post-CD. Lower anticipation of pain medication needs (p=0.0038) was independently associated with the development of PND post-CD. The area under curve (AUC) of this multivariable model (training cohort), internal cross validation (training cohort) and external cross validation (validation cohort) were 0.818 (95% CI, 0.746 to 0.889), 0.785 (95% CI, 0.707 to 0.864) and 0.604 (95% CI, 0.497 to 0.710) respectively. Conclusion: The proposed model performed well in a local population. Further refinement is necessary to test the proposed model in populations with social and cultural differences.

2.
Clin Transplant ; 38(2): e15252, 2024 02.
Article in English | MEDLINE | ID: mdl-38341767

ABSTRACT

Heart transplantation (HT) is the definitive treatment for eligible patients with end-stage heart disease. A major complication of HT is allograft rejection which can lead to graft dysfunction and death. The guiding principle of chronic immunosuppression therapy is to prevent rejection of the transplanted organ while avoiding oversuppression of the immune system, which can cause opportunistic infections and malignancy. The purpose of this review is to describe immunosuppressive management of the HT recipient-including agent-specific pharmacology and pharmacokinetics, outcomes data, adverse effects, clinical considerations, and recent guideline updates. We will also provide recommendations for medical prophylaxis of immunosuppressed patients based on the most recent clinical guidelines. Additionally, we highlight the importance of medical therapy adherence and the effect of social determinants of health on the long-term management of HT. HT recipients are a complex and high-risk population. The objective of this review is to describe basic pharmacotherapy in HT and implications for nurses and pharmacists.


Subject(s)
Heart Transplantation , Nurse Clinicians , Humans , Pharmacists , Immunosuppressive Agents , Heart Transplantation/adverse effects , Immunosuppression Therapy , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/prevention & control
3.
Circulation ; 149(6): 430-449, 2024 02 06.
Article in English | MEDLINE | ID: mdl-37947085

ABSTRACT

BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD. METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets. RESULTS: Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P=0.01). CONCLUSIONS: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Heart Failure , Adult , Humans , Male , Female , Middle Aged , Aged , Creatinine , Glycated Hemoglobin , American Heart Association , Risk Factors , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Heart Failure/diagnosis , Heart Failure/epidemiology , Albumins , Risk Assessment
4.
Circulation ; 148(24): 1982-2004, 2023 12 12.
Article in English | MEDLINE | ID: mdl-37947094

ABSTRACT

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Heart Failure , Male , Adult , Female , United States/epidemiology , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , American Heart Association , Risk Assessment , Kidney , Risk Factors
5.
Circulation ; 148(20): 1636-1664, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37807920

ABSTRACT

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.


Subject(s)
Cardiovascular Diseases , Metabolic Syndrome , Renal Insufficiency, Chronic , United States/epidemiology , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/therapy , American Heart Association , Risk Factors , Kidney , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy
6.
Circulation ; 148(20): 1606-1635, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37807924

ABSTRACT

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.


Subject(s)
Cardiovascular Diseases , Cardiovascular System , Metabolic Syndrome , United States/epidemiology , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/therapy , American Heart Association , Risk Factors , Kidney
8.
Circulation ; 148(7): 622-636, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37439224

ABSTRACT

Although heart transplantation is the preferred therapy for appropriate patients with advanced heart failure, the presence of concomitant renal or hepatic dysfunction can pose a barrier to isolated heart transplantation. Because donor organ supply limits the availability of organ transplantation, appropriate allocation of this scarce resource is essential; thus, clear guidance for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation is urgently required. The purposes of this scientific statement are (1) to describe the impact of pretransplantation renal and hepatic dysfunction on posttransplantation outcomes; (2) to discuss the assessment of pretransplantation renal and hepatic dysfunction; (3) to provide an approach to patient selection for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation and posttransplantation management; and (4) to explore the ethics of multiorgan transplantation.

9.
J Sex Med ; 20(7): 1004-1009, 2023 06 28.
Article in English | MEDLINE | ID: mdl-37147929

ABSTRACT

BACKGROUND: Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment. AIM: The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more "user-friendly pharmacokinetics" as compared with oral tablet administration. METHODS: This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed. OUTCOMES: Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability. RESULTS: Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10 vs 58 minutes, P < .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted. CLINICAL IMPLICATIONS: Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions. STRENGTHS AND LIMITATIONS: The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations. CONCLUSION: Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.


Subject(s)
Erectile Dysfunction , Male , Humans , Aged , Vardenafil Dihydrochloride , Administration, Intranasal , Cross-Over Studies , Biological Availability , Area Under Curve , Tablets , Administration, Oral
10.
Circulation ; 147(2): e4-e30, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36475715

ABSTRACT

Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed.


Subject(s)
Complementary Therapies , Heart Failure , United States , Humans , American Heart Association , Heart Failure/therapy
11.
Circulation ; 144(13): e218-e232, 2021 09 28.
Article in English | MEDLINE | ID: mdl-34407637

ABSTRACT

The misuse of opioids continues to be epidemic, resulting in dependency and a recent upsurge in drug overdoses that have contributed to a significant decrease in life expectancy in the United States. Moreover, recent data suggest that commonly used opioids for the management of pain may produce undesirable pharmacological actions and interfere with critical medications commonly used in cardiovascular disease and stroke; however, the impact on outcomes remains controversial. The American Heart Association developed an advisory statement for health care professionals and researchers in the setting of cardiovascular and brain health to synthesize the current literature, to provide approaches for identifying patients with opioid use disorder, and to address pain management and overdose. A literature and internet search spanning from January 1, 2012, to February 15, 2021, and limited to epidemiology studies, reviews, consensus statements, and guidelines in human subjects was conducted. Suggestions and considerations listed in this document are based primarily on published evidence from this review whenever possible, as well as expert opinion. Several federal and institutional consensus documents and clinical resources are currently available to both patients and clinicians; however, none have specifically addressed cardiovascular disease and brain health. Although strategic tools and therapeutic approaches for recognition of opioid use disorder and safe opioid use are available for health care professionals who manage patients with cardiovascular disease and stroke, high-quality evidence does not currently exist. Therefore, there is an urgent need for more research to identify the most effective approaches to improve care for these patients.


Subject(s)
Analgesics, Opioid/therapeutic use , Brain/drug effects , Cardiovascular Diseases/drug therapy , Adult , Analgesics, Opioid/pharmacology , Female , Humans , Male , Middle Aged
12.
Expert Rev Cardiovasc Ther ; 16(7): 515-526, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29902387

ABSTRACT

INTRODUCTION: This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (If) in the sinoatrial node, thereby reducing heart rate without directly affecting cardiac contraction and relaxation. Clinical data from a phase III trial demonstrated that ivabradine reduced the composite end point of cardiovascular death or hospital admission for worsening systolic HF, while maintaining an acceptable safety profile in patients receiving standard of care therapy. These data, in addition to more recently published guidelines, suggest ivabradine as a promising new treatment option for lowering heart rate after optimizing standard therapy in select patients with chronic HF.


Subject(s)
Benzazepines/therapeutic use , Heart Failure/drug therapy , Heart Rate/drug effects , Adrenergic beta-Antagonists/therapeutic use , Cardiovascular Agents/therapeutic use , Chronic Disease , Heart Failure/physiopathology , Heart Failure, Systolic/drug therapy , Hospitalization , Humans , Ivabradine , Treatment Outcome , Ventricular Dysfunction, Left/drug therapy
13.
Postgrad Med ; 130(3): 299-307, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29596012

ABSTRACT

Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use of NT-proBNP measurement has been suggested in the context of ARNI therapy because its concentrations are not affected by neprilysin inhibition. As biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the effects of individual patient characteristics, such as renal function and age, on biomarker concentrations should be reassessed.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Heart Failure/drug therapy , Heart Failure/physiopathology , Natriuretic Peptide, Brain/drug effects , Natriuretic Peptide, Brain/metabolism , Neprilysin/therapeutic use , Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/pharmacology , Biomarkers , Biphenyl Compounds , Drug Combinations , Drug Therapy, Combination , Humans , Natriuretic Peptide, Brain/blood , Neprilysin/administration & dosage , Neprilysin/pharmacology , Peptide Fragments/blood , Peptide Fragments/drug effects , Randomized Controlled Trials as Topic , Tetrazoles/therapeutic use , Valsartan
14.
Circulation ; 135(22): e1054-e1091, 2017 May 30.
Article in English | MEDLINE | ID: mdl-28446515

ABSTRACT

BACKGROUND AND PURPOSE: Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers. METHODS: The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through December 2016. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or contemporary clinical practice recommendations. RESULTS: A number of biomarkers associated with HF are well recognized, and measuring their concentrations in circulation can be a convenient and noninvasive approach to provide important information about disease severity and helps in the detection, diagnosis, prognosis, and management of HF. These include natriuretic peptides, soluble suppressor of tumorgenicity 2, highly sensitive troponin, galectin-3, midregional proadrenomedullin, cystatin-C, interleukin-6, procalcitonin, and others. There is a need to further evaluate existing and novel markers for guiding therapy and to summarize their data in a standardized format to improve communication among researchers and practitioners. CONCLUSIONS: HF is a complex syndrome involving diverse pathways and pathological processes that can manifest in circulation as biomarkers. A number of such biomarkers are now clinically available, and monitoring their concentrations in blood not only can provide the clinician information about the diagnosis and severity of HF but also can improve prognostication and treatment strategies.


Subject(s)
American Heart Association , Disease Management , Heart Failure/blood , Heart Failure/prevention & control , Inflammation Mediators/blood , Biomarkers/blood , Clinical Trials as Topic/methods , Heart Failure/therapy , Humans , Risk Factors , United States
15.
J Card Fail ; 23(1): 20-28, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27317843

ABSTRACT

BACKGROUND: The prognostic merit of insulin-like growth factor-binding protein 7 (IGFBP7) is unknown in heart failure and preserved ejection fraction (HFpEF). METHODS AND RESULTS: Baseline IGFBP7 (BL-IGFBP7; n = 302) and 6-month change (Δ; n = 293) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years; secondary outcomes included HF events. Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age (R2 = 0.13; P < .0001), amino-terminal pro-B-type NP (R2 = 0.22; P < .0001), and estimated glomerular filtration rate (eGFR; R2 = 0.14; P < .0001), but not with signs/symptoms of HFpEF. BL-IGFBP7 was significantly associated with the primary outcome (hazard ratio [HR] = 1.007 per ng/mL; P < .001), all-cause mortality (HR = 1.008 per ng/mL; P < .001), and HF events (HR = 1.007 per ng/mL; P < .001). IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro-B-type NP and eGFR but not all variables in the I-PRESERVE prediction model. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was significantly associated with decrease in eGFR in patients randomized to irbesartan (R2 = 0.09; P = .002). ΔIGFBP7 was not independently associated with outcome. CONCLUSIONS: Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events, but after multivariable adjustment this association was no longer present. Further studies of IGFBP7 are needed to elucidate its mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00095238.


Subject(s)
Biphenyl Compounds/therapeutic use , Heart Failure/blood , Insulin-Like Growth Factor Binding Proteins/blood , Stroke Volume/physiology , Tetrazoles/therapeutic use , Aged , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Cause of Death/trends , Female , Follow-Up Studies , Heart Failure/drug therapy , Heart Failure/mortality , Hospitalization/statistics & numerical data , Humans , Irbesartan , Male , Prognosis , Risk Factors , Survival Rate/trends , Time Factors , United States/epidemiology
16.
J Cardiovasc Transl Res ; 8(9): 545-53, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26589601

ABSTRACT

Natriuretic peptides (NPs) represent a critical pathway in heart failure (HF). We explored genetic determinants of pharmacodynamic effects of B-type NP (BNP) and changes in plasma cyclic guanosine monophosphate (cGMP) and blood pressure (BP). HF patients (n = 135) received recombinant human BNP (nesiritide) at standard doses, and plasma cGMP levels were measured at baseline and during infusion. We tested the association of 119 single nucleotide polymorphisms (SNPs) in 4 candidate genes (NPR1, NPR2, NPR3, and membrane metallo-endopeptidase (MME)) with the change in cGMP and BP. Gene-based testing for association of genetic variation with endpoints was significant only for MME. Upon individual SNP testing, two loci in MME were associated with ΔcGMP; another (rs16824656) showed association with BP change. In summary, the pharmacodynamic effects of BNP vary substantially in HF patients and are associated with genetic variation in MME. MME genetic variation may be an important determinant of NP-mediated effects in humans.


Subject(s)
Genetic Variation , Guanosine Monophosphate/metabolism , Heart Failure/drug therapy , Natriuretic Peptide, Brain/genetics , Neprilysin/genetics , Aged , Aged, 80 and over , Blood Pressure/drug effects , Cohort Studies , Female , Genotype , Heart Failure/genetics , Heart Failure/physiopathology , Humans , Male , Middle Aged , Neprilysin/administration & dosage , Pharmacogenetics , Sensitivity and Specificity , Severity of Illness Index , Treatment Outcome
17.
Expert Rev Cardiovasc Ther ; 13(7): 743-51, 2015.
Article in English | MEDLINE | ID: mdl-26028173

ABSTRACT

Nesiritide, a recombinant form of B-type natriuretic peptide, is a vasodilator and currently recommended as an additive therapy for patients with acute decompensated heart failure (ADHF) who have been optimized on loop diuretics. With hospitalizations for ADHF rising, appropriate selection of therapy becomes even more important to optimize efficacy and reduce adverse events. Nesiritide has many properties that antagonize the pathophysiologic processes of heart failure and has demonstrated a comparative benefit in previous reports; however, controversy still remains with respect to its efficacy and safety. Based on results from recent clinical trials, nesiritide has been shown to be safe at currently approved doses and strongly considered for the treatment of ADHF in patients who remain symptomatic despite optimal doses of intravenous loop divertics.


Subject(s)
Heart Failure/drug therapy , Natriuretic Agents/therapeutic use , Natriuretic Peptide, Brain/physiology , Acute Disease , Heart Failure/physiopathology , Humans , Natriuretic Agents/physiology , Natriuretic Peptide, Brain/therapeutic use , Natriuretic Peptides/physiology , Natriuretic Peptides/therapeutic use , Randomized Controlled Trials as Topic , Vasodilator Agents/therapeutic use
18.
Expert Rev Cardiovasc Ther ; 13(2): 153-61, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25578159

ABSTRACT

Heart failure continues to be a major public health burden in the USA. With markedly high rates of morbidity and mortality upon diagnosis, effective treatment and prognosis are critical in the management of chronic heart failure. Growing evidence now supports the hypothesis that inflammation plays a key role in the progression and worsening of heart failure. Of the various inflammatory mediators identified, C-reactive protein, an acute phase inflammatory marker, has been associated with poor prognosis in patients with heart failure. Several interventional studies have been investigated to explore C-reactive protein modulation and potential treatment options and health outcomes; however, further studies are warranted before C-reactive protein-targeted therapy may be recommended in the management of heart failure.


Subject(s)
Biomarkers/blood , C-Reactive Protein/metabolism , Cytokines/metabolism , Heart Failure/diagnosis , Inflammation/diagnosis , Animals , Humans , Inflammation/blood , Prognosis
19.
J Card Fail ; 20(9): 662-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24983826

ABSTRACT

BACKGROUND: Natriuretic peptides (NPs) represent a critical pathway in heart failure (HF). However, there is wide individual variability in NP system activity, which could be partly genetic in origin. We explored genetic and nongenetic contributions to B-type natriuretic peptide (BNP) inactivation. METHODS: Chronic HF patients (n = 95) received recombinant human BNP (nesiritide) at standard doses, and BNP levels were measured at baseline, after 2 hours of infusion, and 30 minutes after discontinuation. Genomic DNA was genotyped for 91 single-nucleotide polymorphisms (SNP) in 2 candidate genes. We tested the association of patient characteristics and genotype with 5 pharmacokinetics (PK) parameters: elimination rate constant, ΔBNP, BNP clearance, adjusted BNP clearance, and half-life. Linear regression with pleiotropic analysis was used to test genotype associations with PK. RESULTS: Participants' mean age was 63 years, 44% were female, and 46% were African American. PK parameters varied widely, some >10-fold. HF type (preserved vs reduced) was associated with PK (P < .01), whereas renal function, demographics, and body mass index and were not. Two SNPs in MME (rs989692, rs6798179) and 2 in NPR3 (rs6880564, rs2062708) also had associations with PK (P < .05). CONCLUSIONS: The pharmacokinetics of BNP varies greatly in HF patients, differs by HF type, and possibly by MME or NPR3 genotype. Additional study is warranted.


Subject(s)
Heart Failure/drug therapy , Natriuretic Agents/pharmacokinetics , Natriuretic Peptide, Brain/pharmacokinetics , Neprilysin/genetics , Polymorphism, Single Nucleotide , Receptors, Atrial Natriuretic Factor/genetics , Female , Genotype , Humans , Male , Middle Aged , Prospective Studies , Recombinant Proteins/pharmacokinetics , Stroke Volume
20.
Pharmacotherapy ; 33(5): 529-48, 2013 May.
Article in English | MEDLINE | ID: mdl-23649813

ABSTRACT

Heart failure (HF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a "perfect storm" of factors that predispose patients to medication errors. The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary HF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e.g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause readmissions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams.

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