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1.
J Card Fail ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880247

ABSTRACT

BACKGROUND: Quantitative methods have shown clinically significant heterogeneity in blood volume (BV) profiles in patients with chronic heart failure (HF). How patients' sex might impact this volume heterogeneity and its relationship to cardiac hemodynamics remains to be defined. METHODS: Retrospective analysis of clinical and quantitative BV, plasma volume (PV) and red blood cell (RBC) mass data was undertaken across 3 medical centers. BV was quantitated using nuclear medicine I-131-labeled plasma albumin indicator-dilution methodology with cardiac hemodynamics obtained within 24 hours. RESULTS: In an analysis of 149 males and 106 females, absolute BV was greater, on average, in males (6.9 ± 1.7 vs 5.0 ± 1.2 liters; P < 0.001); however, a wide range in BVs was demonstrated in both sexes (2.9-14.5 liters). Male sex was associated with higher prevalence of large (+ 25% of normal) BV and PV expansions (36% vs 15% and 51% vs 21%, respectively; both P < 0.001). In contrast, female sex was associated with higher prevalence of normal total BV (44% vs 27%; P = 0.005), PV (54% vs 27%; P < 0.001), hypovolemia (23% vs 11%; P = 0.005), and true anemia (42% vs 26%; P < 0.001). Cardiac hemodynamics differed by sex, but only modest associations were demonstrated between volume profiles and cardiac filling pressures. CONCLUSIONS: Findings support unique intravascular volume profiles reflecting sex-specific differences in the prevalence and distributions of total BV, PV and RBC mass profiles in patients with chronic HF. This underscores the importance of recognizing patients' sex as a significant factor influencing volume homeostasis, which needs to be taken into account to individualize volume-management strategies effectively.

2.
Am Heart J ; 271: 178-181, 2024 May.
Article in English | MEDLINE | ID: mdl-38658075

ABSTRACT

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.


Subject(s)
Blood Volume , Heart Failure , Humans , Heart Failure/physiopathology , Heart Failure/mortality , Heart Failure/diagnosis , Prognosis , Blood Volume/physiology , Stroke Volume/physiology , Male , Female , Blood Volume Determination/methods , Aged , Middle Aged
3.
ASAIO J ; 70(2): 93-98, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37862687

ABSTRACT

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.


Subject(s)
Heart-Assist Devices , Thromboembolism , Humans , Warfarin/therapeutic use , Heart-Assist Devices/adverse effects , Anticoagulants/therapeutic use , Thromboembolism/etiology , Thromboembolism/prevention & control , Hemorrhage/etiology , International Normalized Ratio , Retrospective Studies
5.
J Cardiovasc Transl Res ; 16(3): 751-753, 2023 06.
Article in English | MEDLINE | ID: mdl-36515809

ABSTRACT

Studies have shown poor correlation between intra-cardiac pressures and blood volume (BV) measurements including HF. The impact of sex and left ventricular ejection fraction (LVEF) on this relationship has not been studied. We obtained pressure (pulmonary artery diastolic pressure (PADP)) and volume (total blood volume (TBV) and estimated stress blood volume (eSBV)) measurements from HF patients at the time of CardioMEMS implantation. A total of 20 patients were included. There was no significant difference between PADP, TBV, and eSBV between sexes. There was only a moderate correlation between PADP and eSBV in men but not in women or with TBV in both sexes. HFrEF had higher PADP and eSBV than HFpEF. There was a consistent lack of correlation between PADP and both TBV and eSBV. Further studies evaluating mid- to long-term implications of pressure-volume profiles as well as changes following decongestion therapy are warranted to better understand the pressure-volume interplay and determine appropriate decongestion strategy for each pressure-volume phenotype.


Subject(s)
Heart Failure , Male , Female , Humans , Heart Failure/diagnosis , Heart Failure/therapy , Stroke Volume , Ventricular Function, Left , Blood Volume , Prognosis
7.
Article in English | MEDLINE | ID: mdl-33637605

ABSTRACT

INTRODUCTION: Current dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7-14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion. RESULTS: D-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002). CONCLUSIONS: This is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose. TRIAL REGISTRATION NUMBER: NCT02714413.


Subject(s)
Insulin , Sucrose , Blood Glucose , Cross-Over Studies , Fructose , Glucose , Humans , Prospective Studies
8.
J Card Fail ; 27(7): 777-785, 2021 07.
Article in English | MEDLINE | ID: mdl-33640481

ABSTRACT

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Pulmonary Artery/diagnostic imaging , Retrospective Studies , Risk Assessment , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology
10.
Thromb Haemost ; 120(1): 83-93, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31470444

ABSTRACT

In patients requiring dual antiplatelet therapy (DAPT) who also have an indication to be treated with oral anticoagulant (OAC) drugs, aspirin withdrawal reduces the risk of bleeding. There is limited data on the pharmacodynamic effects associated with adding a nonvitamin K antagonist OAC on a background of aspirin and a P2Y12 inhibitor as well as dropping aspirin. Seventy-five patients on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60 mg once daily, Group A), DAPT plus low-dose edoxaban (30 mg once daily, Group B), or DAPT only (Group C) for 10 ± 2 days (Phase I). Afterwards, Groups A and B interrupted aspirin and maintained clopidogrel plus edoxaban for 10 ± 2 days, while patients in Group C maintained DAPT (Phase II). Platelet aggregation and clot kinetics were assessed at baseline, end of Phase I, and end of Phase II using thrombelastography (TEG), light transmittance aggregometry (LTA), VerifyNow P2Y12, and serum thromboxane-B2. The primary endpoint was the comparison of maximum amplitude (MA) measured by TEG, a measure of clot strength, between patients on DAPT plus high-dose edoxaban and patients on DAPT only. Edoxaban prolonged in a dose-dependent manner speed of thrombin generation (TEG R; Group A: 7.7 [6.8-8.7] vs. Group B: 7.4 [6.4-8.5] vs. Group C: 6.3 [5.7-7.0]; p = 0.05) but did not affect other markers of clot kinetics, including TEG MA (Group A: 63 [61-64] vs. Group B: 65 [63-67] vs. Group C: 64 [63-65]; p = 0.10). After aspirin discontinuation, platelet reactivity assessed by LTA using thrombin receptor activating peptide as agonist increased to a greater extent with low-dose edoxaban. Stopping aspirin did not affect markers of P2Y12 reactivity and had no or marginal effects on clot kinetics, but increased markers sensitive to cyclooxygenase-1 blockade.


Subject(s)
Anticoagulants/therapeutic use , Aspirin/therapeutic use , Clopidogrel/therapeutic use , Coronary Artery Disease/drug therapy , Dual Anti-Platelet Therapy/methods , Pyridines/therapeutic use , Thiazoles/therapeutic use , Aged , Blood Coagulation , Coronary Artery Disease/mortality , Cyclooxygenase 1/metabolism , Drug Interactions , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Receptors, Purinergic P2Y12/metabolism , Survival Analysis
12.
JACC Cardiovasc Interv ; 12(16): 1538-1549, 2019 08 26.
Article in English | MEDLINE | ID: mdl-31377269

ABSTRACT

OBJECTIVES: The aim of this study was to assess if intravenous methylnaltrexone can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor. BACKGROUND: Morphine delays the onset of action of oral P2Y12 receptor inhibitors, including ticagrelor, by inhibiting gastric emptying and leading to delayed drug absorption. Methylnaltrexone is a peripheral opioid receptor antagonist that has the potential to prevent opioid-induced peripherally mediated side effects (e.g., gastric emptying inhibition) without affecting analgesia. METHODS: In this prospective, randomized, double-blind, placebo-controlled, crossover study, aspirin-treated patients with stable coronary artery disease (n = 30) were randomized to receive methylnaltrexone (0.3 mg/kg intravenous) or matching placebo. After methylnaltrexone or placebo administration, all patients received morphine (5 mg intravenous). This was followed 15 min later by a 180-mg loading dose of ticagrelor. Patients crossed over to the alternative study treatment after 7 ± 2 days of washout. PK and PD assessments were performed at 12 time points (6 pre- and 6 post-crossover). PK analysis included measurement of plasma levels of ticagrelor and its major active metabolite (AR-C124910XX). PD assessments included VerifyNow P2Y12, light transmittance aggregometry, and vasodilator-stimulated phosphoprotein. RESULTS: Only marginal changes in plasma levels of ticagrelor (and its major active metabolite) were observed with ticagrelor: maximum plasma concentration and area under the plasma concentration versus time curve from time 0 to the last measurable concentration were 38% and 30% higher, respectively, in patients receiving methylnaltrexone compared with those receiving placebo, but no differences in time to maximum plasma concentration were observed. There were no differences in P2Y12 reaction units by VerifyNow P2Y12 between groups at each time point, including 2 h (the primary endpoint; p = 0.261). Similarly, there were no differences in PD markers assessed by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. CONCLUSIONS: In patients with coronary artery disease receiving morphine, intravenous administration of the peripheral opioid receptor antagonist methylnaltrexone leads to only marginal changes in plasma levels of ticagrelor and its major metabolite, without affecting levels of platelet reactivity. (Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine; NCT02403830).


Subject(s)
Analgesics, Opioid/administration & dosage , Blood Platelets/drug effects , Coronary Artery Disease/drug therapy , Morphine/administration & dosage , Naltrexone/analogs & derivatives , Narcotic Antagonists/administration & dosage , Platelet Aggregation Inhibitors/pharmacokinetics , Ticagrelor/pharmacokinetics , Administration, Intravenous , Administration, Oral , Aged , Analgesics, Opioid/adverse effects , Blood Platelets/metabolism , Cell Adhesion Molecules/blood , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Cross-Over Studies , Double-Blind Method , Drug Interactions , Female , Florida , Gastric Emptying/drug effects , Gastrointestinal Absorption/drug effects , Humans , Male , Microfilament Proteins/blood , Middle Aged , Morphine/adverse effects , Naltrexone/administration & dosage , Naltrexone/adverse effects , Narcotic Antagonists/adverse effects , Phosphoproteins/blood , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Quaternary Ammonium Compounds/administration & dosage , Quaternary Ammonium Compounds/adverse effects , Ticagrelor/administration & dosage , Ticagrelor/adverse effects , Treatment Outcome
13.
J Am Heart Assoc ; 8(14): e011813, 2019 07 16.
Article in English | MEDLINE | ID: mdl-31280637

ABSTRACT

Background The effect of implantable cardioverter defibrillators ( ICD ) in patients with continuous flow left ventricular assist devices ( LVAD s) on outcomes has not been evaluated in a randomized clinical trial. Methods and Results This is a retrospective single-center study that included patients who underwent continuous flow LVAD implantation at the Cleveland Clinic between October 2004 and March 2017. Patients were evaluated according to the presence or absence of ICD at the time of LVAD insertion. Among 486 patients in the study cohort, 387 (79.6%) had an ICD before LVAD insertion. Patients with ICD before LVAD were older and had lower use of pre- LVAD inotropes, extracorporeal membrane oxygenation, and mechanical ventilation. There were 81 patients (21.4% of patients with ICD ) who required 93 procedures after LVAD : 74 generator exchanges, 12 lead revisions, and 7 complete system removals because of infection. Of the 99 patients without ICD , 52 (53%) underwent ICD implantation: 29 for primary prevention and 23 for secondary prevention. Patients were followed for a median of 401 (interquartile range 150-966) days. The presence of a pre- LVAD ICD was not associated with mortality in a multivariable model (hazard ratio 1.19, 95% CI 0.73-1.93, P=0.492), nor was the presence of an ICD at any point when analyzed as a time-varying covariate (hazard ratio 1.05, 95% CI 0.50-2.20, P=0.907). Conclusions There is no apparent mortality benefit associated with an ICD in a contemporary cohort of patients with continuous flow LVAD s to balance considerable morbidity involving ICD -related procedures and complications.


Subject(s)
Defibrillators, Implantable/statistics & numerical data , Heart Failure/therapy , Heart-Assist Devices/statistics & numerical data , Mortality , Postoperative Complications/epidemiology , Prosthesis Implantation/statistics & numerical data , Prosthesis-Related Infections/epidemiology , Adult , Aged , Cardiotonic Agents/therapeutic use , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Humans , Male , Middle Aged , Postoperative Complications/surgery , Primary Prevention , Proportional Hazards Models , Prosthesis-Related Infections/surgery , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Secondary Prevention
16.
Minerva Cardioangiol ; 64(6): 595-602, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27119370

ABSTRACT

BACKGROUND: Galectin-3 is a recently developed biomarker of fibrosis, which may play a role in cardiac remodeling and associated with both the progression and severity of heart failure (HF). METHODS: A prospective cohort study of 190 patients with documented prior myocardial infarction and chronic HF (NYHA class II-IV) was conducted. Patients were divided into 3 groups based on their NYHA functional class. Levels of galectin-3, NT-proBNP, CRP, IL-6, oxidized-LDL, extracellular superoxide dismutase (EC-SOD), 3-nitrotyrosine, SH-groups, cystatin-C were determined. Follow-up period was 26 months, and all-cause mortality was determined as the primary endpoint. Statistical analysis was performed and statistical significance was set at P<0.05. RESULTS: The cytokines hs-CRP, IL-6 and markers of oxidative stress had significant positive correlation with plasma galectin-3 levels in all groups of patients. The level of galectin-3 was significantly different between the groups (P<0.05). Galectin-3 was found to be the most sensitive and specific value in determination of 26 months mortality in patients with chronic HF. Logistic regression analysis showed that age, galectin-3 and cystatin-C were associated with death during the follow up period. CONCLUSIONS: Galectin-3 levels are elevated in patients with chronic HF across all NYHA functional classes. Galectin-3 shows positive correlation with markers of oxidative stress, inflammation and kidney dysfunction. Galectin-3 levels and cystatin-C levels are independent predictors of 26-month mortality in patients with chronic HF. Patients with cystatin-C level >2800 pg/mL carry a worse prognosis. Galectin-3 level >21 ng/mL associated with increased mortality.


Subject(s)
Galectin 3/blood , Heart Failure/blood , Inflammation/blood , Kidney Diseases/blood , Oxidative Stress , Aged , Biomarkers/blood , Blood Proteins , Cohort Studies , Cytokines/blood , Female , Galectins , Heart Failure/complications , Humans , Kidney Diseases/complications , Male , Middle Aged , Myocardial Infarction/blood , Prognosis , Prospective Studies
17.
Case Rep Cardiol ; 2015: 291079, 2015.
Article in English | MEDLINE | ID: mdl-26146571

ABSTRACT

Infective endocarditis (IE) is an infection of the endocardium that involves valves and adjacent mural endocardium or a septal defect. Local complications include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses. If left untreated, IE is generally fatal. Diagnosing IE can be straightforward in patients with the typical oslerian manifestations such as bacteremia, evidence of active valvulitis, peripheral emboli, and immunologic vascular phenomena. In the acute course, however, the classic peripheral stigmata may be few or absent, particularly among intravenous drug abuse (IVDA) patients in whom IE is often due to a S. aureus infection of right-sided heart valves. We present a complicated case of a very aggressive native aortic valve MSSA (methicillin sensitive Staphylococcus aureus) IE in a young adult male with a past medical history of bicuspid aortic valve and IV drug abuse. His clinical course was complicated by aortic valve destruction and development of third-degree AV block, as well as an aorto-left atrial fistula requiring emergent operation for AV replacement and patch repair. The patient required two reoperations for recurrent endocarditis and its complications.

18.
Am J Cardiol ; 115(4): 461-5, 2015 Feb 15.
Article in English | MEDLINE | ID: mdl-25529543

ABSTRACT

Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke that is not included in the usual cardioembolic risk assessments for patients with atrial fibrillation (AF). The aim of this study was to investigate the impact of OSA on stroke rate in patients with AF. Patients with AF and new diagnoses of OSA were identified from retrospective chart review. Those with histories of stroke at the time of the sleep study were excluded. The primary outcome was the incidence of stroke, determined by a physician investigator blinded to the results of polysomnography. Subgroup analysis was performed among different CHADS2 and CHA2DS2-VASc scores. Of 5,138 patients screened for OSA, 402 (7.7%) had AF and 332 (6.4%) met the inclusion criteria. Among the study population, the occurrence of first-time stroke was 22.9%. Ischemic stroke was more common in patients with OSA compared with patients without (25.4% vs 8.2% respectively, p = 0.006). After controlling for age, male gender, and coronary artery disease, the association between OSA and stroke remained statistically significant, with an adjusted odds ratio of 3.65 (95% confidence interval 1.252 to 10.623). A positive dose effect of the apnea-hypopnea index on the rate of stroke was observed (p = 0.0045). Subgroup analysis showed significantly higher rates of stroke in patients with CHADS2 scores of 0 and CHA2DS2-VASc scores of 0 and 1 and co-morbid OSA. In conclusion, OSA in patients with AF is an independent predictor of stroke. This association may have important clinical implications in ischemic stroke risk stratification.


Subject(s)
Atrial Fibrillation/complications , Risk Assessment/methods , Sleep Apnea, Obstructive/complications , Stroke/epidemiology , Aged , Connecticut/epidemiology , Electrocardiography , Female , Follow-Up Studies , Humans , Incidence , Male , Polysomnography , Prognosis , Retrospective Studies , Risk Factors , Sleep Apnea, Obstructive/physiopathology , Stroke/etiology
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