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Journal of the American College of... Jan 2020Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher... (Review)
Review
Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher in African-American women and in women with older maternal age, hypertensive disorders of pregnancy, and multiple gestation pregnancies. Symptoms of heart failure mimic those of normal pregnancy, often resulting in a delay in diagnosis and preventable complications. Echocardiography showing decreased myocardial function is essential for the diagnosis. Medical management is similar to heart failure with reduced ejection fraction of other etiologies, but adjustments during pregnancy are necessary to ensure fetal safety. Variable outcomes include complete recovery, persistent heart failure, arrhythmias, thromboembolic events, and death. Subsequent pregnancy confers substantial risk of relapse and even death if there is incomplete myocardial recovery. Additional research about the etiology, optimal therapy including the use of bromocriptine, long-term outcomes, and duration of treatment after recovery are needed.
Topics: Cardiomyopathies; Cardiovascular Agents; Female; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Review Literature as Topic
PubMed: 31948651
DOI: 10.1016/j.jacc.2019.11.014 -
Circulation Research May 2019Approximately half of the patients with signs and symptoms of heart failure have a left ventricular ejection fraction that is not markedly abnormal. Despite the... (Review)
Review
Approximately half of the patients with signs and symptoms of heart failure have a left ventricular ejection fraction that is not markedly abnormal. Despite the historically initial surprise, heightened risks for heart failure specific major adverse events occur across the broad range of ejection fraction, including normal. The recognition of the magnitude of the problem of heart failure with preserved ejection fraction in the past 20 years has spurred an explosion of clinical investigation and growing intensity of informative outcome trials. This article addresses the historic development of this component of the heart failure syndrome, including the epidemiology, pathophysiology, and existing and planned therapeutic studies. Looking forward, more specific phenotyping and even genotyping of subpopulations should lead to improvements in outcomes from future trials.
Topics: Cardiovascular Agents; Comorbidity; Healthy Lifestyle; Heart Failure; Humans; Recovery of Function; Risk Factors; Risk Reduction Behavior; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left
PubMed: 31120821
DOI: 10.1161/CIRCRESAHA.119.313572 -
The New England Journal of Medicine Oct 2013
Review
Topics: Cardiotonic Agents; Cardiovascular Agents; Diagnosis, Differential; Fluid Therapy; Humans; Lactic Acid; Shock; Vasoconstrictor Agents; Vasodilator Agents
PubMed: 24171518
DOI: 10.1056/NEJMra1208943 -
Arteriosclerosis, Thrombosis, and... Mar 2020Peripheral artery disease is an atherosclerotic disease of the lower extremities associated with high cardiovascular mortality. Management of this condition may include... (Review)
Review
Peripheral artery disease is an atherosclerotic disease of the lower extremities associated with high cardiovascular mortality. Management of this condition may include lifestyle modifications, medical management, endovascular repair, or surgery. The medical approach to peripheral artery disease is multifaceted and includes cholesterol reduction, antiplatelet therapy, anticoagulation, peripheral vasodilators, blood pressure management, exercise therapy, and smoking cessation. Adherence to this regimen can reduce limb-related complications like critical limb ischemia and amputation, as well as systemic complications of atherosclerosis like stroke and myocardial infarction. Relative to coronary artery disease, peripheral artery disease is an undertreated condition. In this article, we explore the evidence behind medical therapies for the management of peripheral artery disease.
Topics: Amputation, Surgical; Cardiovascular Agents; Evidence-Based Medicine; Hemodynamics; Humans; Limb Salvage; Peripheral Arterial Disease; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Vascular Surgical Procedures
PubMed: 31996023
DOI: 10.1161/ATVBAHA.119.312142 -
Nature Reviews. Cardiology Sep 2021Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is... (Review)
Review
Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is CYP2C19 genotyping to predict clopidogrel response and assist in selecting antiplatelet therapy after percutaneous coronary intervention. Additional examples include genotyping to guide warfarin dosing and statin prescribing. Increasing evidence exists on outcomes with genotype-guided cardiovascular therapies from multiple randomized controlled trials and observational studies. Pharmacogenetic evidence is accumulating for additional cardiovascular medications. However, data for many of these medications are not yet sufficient to support the use of genotyping for drug prescribing. Ultimately, pharmacogenetics might provide a means to individualize drug regimens for complex diseases such as heart failure, in which the treatment armamentarium includes a growing list of medications shown to reduce morbidity and mortality. However, sophisticated analytical approaches are likely to be necessary to dissect the genetic underpinnings of responses to drug combinations. In this Review, we examine the evidence supporting pharmacogenetic testing in cardiovascular medicine, including that available from several clinical trials. In addition, we describe guidelines that support the use of cardiovascular pharmacogenetics, provide examples of clinical implementation of genotype-guided cardiovascular therapies and discuss opportunities for future growth of the field.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Pharmacogenetics
PubMed: 33953382
DOI: 10.1038/s41569-021-00549-w -
JACC. Cardiovascular Interventions Jul 2018Aneurysmal dilation of coronary arteries is observed in up to 5% of patients undergoing coronary angiography. Due to their poorly elucidated underlying mechanisms, their... (Review)
Review
Aneurysmal dilation of coronary arteries is observed in up to 5% of patients undergoing coronary angiography. Due to their poorly elucidated underlying mechanisms, their variable presentations, and the lack of largescale outcome data on their various treatment modalities, coronary artery aneurysms and coronary ectasia pose a challenge to the managing clinician. This paper aims to provide a succinct review of aneurysmal coronary disease, with a special emphasis on the challenges associated with its interventional treatment.
Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Coronary Aneurysm; Coronary Artery Bypass; Humans; Ligation; Percutaneous Coronary Intervention; Risk Factors; Stents; Treatment Outcome
PubMed: 29976357
DOI: 10.1016/j.jcin.2018.02.041 -
Cardiology 2018Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million... (Review)
Review
Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the "classical" obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.
Topics: Adrenergic beta-Antagonists; Angina, Stable; Calcium Channel Blockers; Cardiovascular Agents; Chest Pain; Humans; Ivabradine; Nicorandil; Patient Selection; Practice Guidelines as Topic; Ranolazine; Treatment Outcome; Trimetazidine
PubMed: 29874661
DOI: 10.1159/000487936 -
Journal of the American College of... Feb 2019Cardiovascular disease complicating pregnancy is rising in prevalence secondary to advanced maternal age, cardiovascular risk factors, and the successful management of... (Review)
Review
Cardiovascular disease complicating pregnancy is rising in prevalence secondary to advanced maternal age, cardiovascular risk factors, and the successful management of congenital heart disease conditions. The physiological changes of pregnancy may alter drug properties affecting both mother and fetus. Familiarity with both physiological and pharmacological attributes is key for the successful management of pregnant women with cardiac disease. This review summarizes the published data, available guidelines, and recommendations for use of cardiovascular medications during pregnancy. Care of the pregnant woman with cardiovascular disease requires a multidisciplinary team approach with members from cardiology, maternal fetal medicine, anesthesia, and nursing.
Topics: Breast Feeding; Cardiovascular Agents; Connective Tissue Diseases; Female; Hematologic Agents; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Pulmonary; Pregnancy; Pregnancy Complications, Cardiovascular; Teratogens
PubMed: 30704579
DOI: 10.1016/j.jacc.2018.10.075 -
Acta Pharmacologica Sinica Sep 2022Colchicine is an ancient herbal drug derived from Colchicum autumnale. It was first used to treat familial Mediterranean fever and gout. Based on its unique efficacy as... (Review)
Review
Colchicine is an ancient herbal drug derived from Colchicum autumnale. It was first used to treat familial Mediterranean fever and gout. Based on its unique efficacy as an anti-inflammatory agent, colchicine has been used in the therapy of cardiovascular diseases including coronary artery disease, atherosclerosis, recurrent pericarditis, vascular restenosis, heart failure, and myocardial infarction. More recently, colchicine has also shown therapeutic efficacy in alleviating cardiovascular complications of COVID-19. COLCOT and LoDoCo2 are two milestone clinical trials that confirm the curative effect of long-term administration of colchicine in reducing the incidence of cardiovascular events in patients with coronary artery disease. There is growing interest in studying the anti-inflammatory mechanisms of colchicine. The anti-inflammatory action of colchicine is mediated mainly through inhibiting the assembly of microtubules. At the cellular level, colchicine inhibits the following: (1) endothelial cell dysfunction and inflammation; (2) smooth muscle cell proliferation and migration; (3) macrophage chemotaxis, migration, and adhesion; (4) platelet activation. At the molecular level, colchicine reduces proinflammatory cytokine release and inhibits NF-κB signaling and NLRP3 inflammasome activation. In this review, we summarize the current clinical trials with proven curative effect of colchicine in treating cardiovascular diseases. We also systematically discuss the mechanisms of colchicine action in cardiovascular therapeutics. Altogether, colchicine, a bioactive constituent from an ancient medicinal herb, exerts unique anti-inflammatory effects and prominent cardiovascular actions, and will charter a new page in cardiovascular medicine.
Topics: Anti-Inflammatory Agents; Cardiovascular Agents; Colchicine; Coronary Artery Disease; Humans; Myocardial Infarction; COVID-19 Drug Treatment
PubMed: 35046517
DOI: 10.1038/s41401-021-00835-w -
JAMA Sep 2023Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen.
OBJECTIVE
To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin.
DESIGN, SETTING, AND PARTICIPANTS
This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands.
INTERVENTIONS
The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher.
MAIN OUTCOMES AND MEASURES
Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers.
RESULTS
Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed.
CONCLUSION
Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04472676.
Topics: Adult; Female; Humans; American Indian or Alaska Native; Apoprotein(a); Lipoprotein(a); Administration, Oral; Cardiovascular Agents; Hypolipidemic Agents; Double-Blind Method; Male; Adolescent; Young Adult; Middle Aged; Dose-Response Relationship, Drug; White; Black or African American; Racial Groups
PubMed: 37638695
DOI: 10.1001/jama.2023.16503