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Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology.
Limberg, JK, Casey, DP, Trinity, JD, Nicholson, WT, Wray, DW, Tschakovsky, ME, Green, DJ, Hellsten, Y, Fadel, PJ, Joyner, MJ, et al
American journal of physiology. Heart and circulatory physiology. 2020;(2):H301-H325
Abstract
The introduction of duplex Doppler ultrasound almost half a century ago signified a revolutionary advance in the ability to assess limb blood flow in humans. It is now widely used to assess blood flow under a variety of experimental conditions to study skeletal muscle resistance vessel function. Despite its pervasive adoption, there is substantial variability between studies in relation to experimental protocols, procedures for data analysis, and interpretation of findings. This guideline results from a collegial discussion among physiologists and pharmacologists, with the goal of providing general as well as specific recommendations regarding the conduct of human studies involving Doppler ultrasound-based measures of resistance vessel function in skeletal muscle. Indeed, the focus is on methods used to assess resistance vessel function and not upstream conduit artery function (i.e., macrovasculature), which has been expertly reviewed elsewhere. In particular, we address topics related to experimental design, data collection, and signal processing as well as review common procedures used to assess resistance vessel function, including postocclusive reactive hyperemia, passive limb movement, acute single limb exercise, and pharmacological interventions.
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2.
Beta-Blockers, Calcium Channel Blockers, and Mortality in Stable Coronary Artery Disease.
Cruz Rodriguez, JB, Alkhateeb, H
Current cardiology reports. 2020;(3):12
Abstract
PURPOSE OF REVIEW To examine the current clinical evidence behind the use of calcium channel blockers (CCB) and beta-blockers (BB) for the treatment of patients with stable coronary artery disease (SCAD) and their effect on mortality. RECENT FINDINGS Current evidence suggests that BB use as a first line antianginal medication is associated with lower 5-year all-cause mortality only in patients who had MI within a year. This could be driven due to their effects reducing the sympathetic neuro-hormonal activation of more acutely ill patients. The use of CCB as an antianginal therapy, although proven effective in multiple trials both as monotherapy and combined with other agents, has not shown mortality benefit. Both BB and CCB are effective antianginals, and the selection among them depends on the patient clinical presentation and comorbidities. BB are the only ones that have shown survival benefit in SCAD, particularly the first year post-MI.
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3.
Ivabradine: a new frontier in the treatment of stable coronary artery disease and chronic heart failure.
Gammone, MA, Riccioni, G, D'Orazio, N
La Clinica terapeutica. 2020;(5):e449-e453
Abstract
Ivabradine (IVA) is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. This pure heart rate-lowering agent possesses well-documented antianginal and anti-ischemic properties comparable to well-established antianginal agents, such as β-blockers and calcium channel blockers. IVA lowers heart rate (HR) without affecting contractility or vascular tone and it is licensed for HR control in chronic heart diseases. The heart rate reduction is beneficial in patients with coronary artery disease (CAD), chronic stable angina pectoris, and chronic heart failure (CHF). Published trials documented not only pharmacodynamic and pharmacokinetic properties but also acceptable tolerance and safety profile of IVA, compared to other currently used cardiovascular drugs, including betablockers. The aim of this review is to describe recent evidences with IVA an interesting medicament, able to lower HR by selective inhibition of the If current, and to describe its applications.
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4.
The Sweet Spot: Heart Failure Prevention with SGLT2 Inhibitors.
Vardeny, O
The American journal of medicine. 2020;(2):182-185
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of medications that reduce plasma glucose concentrations through an insulin-independent mechanism of increased urinary glucose excretion, with concomitant natriuresis and diuresis. Clinical outcomes trials with SGLT2 inhibitors revealed a cardioprotective benefit among patients with diabetes mellitus, with a consistent reduction in hospitalization for heart failure. As such, the 2018 updated US and European treatment guidelines for diabetes mellitus incorporated SGLT2 inhibitors as second-line glucose-lowering agents after metformin. Although well tolerated, there are known adverse effects with SGLT2 inhibitors that require clinical monitoring, such as genital mycotic infections, diabetic ketoacidosis, volume depletion particularly in the setting of concomitant diuretic use, and lower limb amputations with canagliflozin. Ongoing clinical trials will uncover the potential benefit of SGLT2 inhibitors in patients with prevalent heart failure with or without diabetes mellitus.
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5.
Diabetes without Manifest Cardiovascular Disease: A Novel Approach in Risk Stratification and Treatment Selection.
Andari, E, Arnaout, S, Azar, ST, Chammas, E, Jambart, S, Saleh, M, Nemr, R, Sarkis, A
Current diabetes reviews. 2020;(8):869-873
Abstract
BACKGROUND Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D. INTRODUCTION Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial. METHODS This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories. RESULTS AND CONCLUSION The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals.
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6.
Strategies for Appropriate Selection of SGLT2-i vs. GLP1-RA in Persons with Diabetes and Cardiovascular Disease.
Dhindsa, DS, Mehta, A, Sandesara, PB, Thobani, A, Brandt, S, Sperling, LS
Current cardiology reports. 2019;(9):100
Abstract
PURPOSE OF REVIEW This review will serve to highlight the clinical rationale used in the selection of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) or glucagon-like peptide 1 receptor agonists (GLP1-ra). RECENT FINDINGS SGLT2-i and GLP1-ra are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit in multiple cardiovascular outcomes trials (CVOTs), with benefits that are consistent across class of medication. Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and glucagon-like peptide 1 receptor agonists (GLP1-ra) are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit. Given the unique side effect and benefit profiles, appropriate consideration of these agents with a focus on cardiovascular risk reduction requires an individualized approach.
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7.
Cardiovascular Disease in Type 2 Diabetes: A Review of Sex-Related Differences in Predisposition and Prevention.
Al-Salameh, A, Chanson, P, Bucher, S, Ringa, V, Becquemont, L
Mayo Clinic proceedings. 2019;(2):287-308
Abstract
Type 2 diabetes mellitus is a major risk factor for cardiovascular disease. However, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to sex. In recent years, large meta-analyses have confirmed that women with type 2 diabetes have a higher relative risk of incident coronary heart disease, fatal coronary heart disease, and stroke compared with their male counterparts. The reasons for these disparities are not completely elucidated. A greater burden of cardiometabolic risk in women was proposed as a partial explanation. Indeed, several studies suggest that women experience a larger deterioration in major cardiovascular risk factors and put on more weight than do men during their transition from normoglycemia to overt type 2 diabetes. This excess weight is associated with higher levels of biomarkers of endothelial dysfunction, inflammation, and procoagulant state. Moreover, sex differences in the prescription and use of some cardiovascular drugs may compound an "existing" disparity. We searched PubMed for articles published in English and French, by using the following terms: ("cardiovascular diseases") AND ("diabetes mellitus") AND ("sex disparity" OR "sex differences" OR "sex related differences" OR "sex-related differences" OR "sex disparities"). In this article, we review the available literature on the sex aspects of primary and secondary prevention of cardiovascular disease in people with type 2 diabetes, in the predisposition to cardiovascular disease in those people, and in the control of diabetes and associated cardiovascular risk factors.
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8.
A review of interventions ≥ 6 months by pharmacists on adherence to medicines in cardiovascular disease: Characteristics of what works and what doesn't.
Doggrell, SA
Research in social & administrative pharmacy : RSAP. 2019;(2):119-129
Abstract
BACKGROUND Nonadherence to cardiovascular medicines occurs in 60% of subjects with chronic cardiovascular disease and leads to poor outcomes. In an attempt to improve adherence and cardiovascular outcomes, interventions are often used. Interventions may involve a pharmacist, but it is not always clear whether these are effective. OBJECTIVES The primary objective of this review is to determine whether interventions by pharmacists, alone, discussing adherence to medicines, improve adherence to medicines for cardiovascular disease. Subsequently, the review links the characteristics of the individual studies with effectiveness or lack of effect. The second objective of this review is to consider whether any improvement in adherence with interventions by pharmacist is associated with better clinical outcomes. METHODS A literature search of PubMed and CINAHL for 'pharmacist', 'medicine' with 'adherence' or 'compliance' or 'persistence' was undertaken. To be included in this review, papers had to be of a pharmacist working alone and in person in an intervention of subjects with hypertension, hyperlipidemia (prior to or after a coronary artery event) or heart failure. The paper had to be published in a peer review journal, with a measure of adherence to medicines. The effectiveness of the intervention had to be evaluated after ≥6 months. RESULTS Only 3 out of 8 interventions by pharmacists in hypertension, and 5 out of 12 interventions in subjects with hyperlipidemia led to improved adherence to medicines. In contrast, all 6 interventions by a pharmacist in subjects with heart failure were successful in improving adherence. One characteristic of successful interventions by pharmacists to improve adherence to cardiovascular medicines is that they must be more than brief/single interventions. A second characteristic is that the intervention should not involve subjects who are already highly adherent, as it is unlikely adherence can be improved in this population. Only 2 of 3 successful interventions in hypertension were associated with small reductions in blood pressure, and only one intervention in hyperlipidemia was shown to decrease LDL-cholesterol to a small extent. In subjects with heart failure, 5 of the 6 successful studies of the successful interventions by pharmacists to increase adherence also showed improved clinical outcomes. CONCLUSIONS When planning an intervention to improve adherence to medicines and cardiovascular outcomes in subjects with hypertension or hyperlipidemic, by a pharmacist alone, or as part of a multi-faceted interventions, it is essential to use an intervention that has been shown to be effective, as most interventions are not effective at improving adherence or only improve adherence and clinical outcomes to a small extent. In heart failure, there is well documented evidence of interventions by pharmacists that do improve clinical outcomes, which should be adopted widely.
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9.
Is Heart Failure with Preserved Ejection Fraction a Kidney Disorder?
Shah, KS, Fang, JC
Current hypertension reports. 2019;(11):86
Abstract
PURPOSE OF REVIEW Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome of exertional intolerance, cardiac dysfunction, and fluid overload and is associated with significant morbidity and mortality. RECENT FINDINGS As our understanding of this syndrome has evolved, we are beginning to recognize the similarities and associations with chronic kidney disease (CKD). Salt and fluid retention are common in CKD and may be the sentinel event leading ultimately to the syndrome of HFpEF. Mechanisms linking both disease states include hypervolemia, inflammation, and endothelial dysfunction, which are also common to comorbidities that drive both HFpEF and CKD. In this review, we will discuss recent clinical research focusing on HFpEF, CKD, and comorbidities including hypertension and diabetes mellitus. We will review strategies for volume management and novel therapeutic approaches with new classes of drugs, including sodium-glucose cotransporters and angiotensin receptor/neprilysin inhibitors, which may work through targeting of both the heart and the kidney. Lastly, we emphasize why focusing on the alleviation of factors provoking renal injury and slowing the progression of renal dysfunction may provide the most therapeutic benefit in patients who have been diagnosed with HFpEF.
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10.
Update on the ECG component of the CiPA initiative.
Vicente, J
Journal of electrocardiology. 2018;(6S):S98-S102
Abstract
The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is validating a new paradigm for assessing proarrhythmic potential of drugs that goes beyond hERG block and QT prolongation. Based on in vitro data of the drug's effects on multiple cardiac ion channel currents, CiPA's in silico model of the human cardiomyocyte will classify drugs as low, intermediate or high risk for torsade de pointes. Under CiPA, early phase 1 ECG data will be used to determine if there are unexpected ion channel effects in humans compared to the in vitro ion channel data. CiPA's ECG biomarker working group identified the heart rate corrected J-Tpeak interval (J-Tpeakc, from the end of the QRS to the peak of the T-wave) as the best of 12 ECG biomarkers to detect late sodium current block in presence of hERG block. While predominant hERG blockers prolonged QTc and J-Tpeakc, "balanced" ion channel blocking drugs (hERG + late sodium and/or calcium block) prolonged QTc without prolonging J-Tpeakc. This manuscript reviews the ECG component of CiPA and provides a description of the ECG methods used in the CiPA ECG validation clinical study.