Showing papers in "Clinical Cardiology in 2018"

Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.

Abstract: It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to 4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

Sex differences in heart failure

Abstract: Heart failure (HF) numbers continue to grow in the United States and approximately 50% of patients living with HF are women. For the provider, it is critical to understand the role that gender plays in recognition, diagnosis, and management. The purpose of this literature review is to highlight the prevalence of heart failure in women and discuss gender variations in epidemiology, symptoms, pharmacology, and treatment as well as examine the representation of women in clinical trials.

Adverse pregnancy outcomes and future maternal cardiovascular disease.

Abstract: Cardiovascular disease (CVD) remains the leading cause of death in women. Although traditional risk factors increase later-life CVD, pregnancy-associated complications additionally influence future CVD risk in women. Recent guidelines for the prevention of CVD in women have added adverse pregnancy outcomes as major CVD risk factors. Studies have shown that women with a history of preeclampsia, gestational diabetes, preterm delivery, and delivery of a small-for-gestational-age infant have an increased risk of developing cardiometabolic risk factors and subsequent CVD. A history of multiple adverse pregnancy outcomes further increases this risk. It has been suggested that these pregnancy complications may unmask preexisting elevated CVD risk; however, whether the pathophysiologic changes underlying these conditions directly result in long-term cardiovascular damage is unclear. The purpose of this review was to highlight the associations between adverse pregnancy outcomes and future CVD, and to emphasize the importance of considering pregnancy history in assessing a woman's CVD risk. Targeted efforts to initiate screening and risk-reduction strategies in women with prior history of pregnancy complications, particularly lifestyle modification, may help decrease the burden of CVD in women.

A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications.

Abstract: BACKGROUND Cardiovascular disease (CVD) is a major economic burden in the United States. CVD risk factors, particularly hypertension and hypercholesterolemia, are typically treated with drug therapy. Five-year efficacy of such drugs to prevent CVD is estimated to be 5%. Plant-based diets have emerged as effective mitigators of these risk factors. HYPOTHESIS The implementation of a defined, plant-based diet for 4 weeks in an outpatient clinical setting may mitigate CVD risk factors and reduce patient drug burden. METHODS Participants consumed a plant-based diet consisting of foods prepared in a defined method in accordance with a food-classification system. Participants consumed raw fruits, vegetables, seeds, and avocado. All animal products were excluded from the diet. Participant anthropometric and hemodynamic data were obtained weekly for 4 weeks. Laboratory biomarkers were collected at baseline and at 4 weeks. Medication needs were assessed weekly. Data were analyzed using paired-samples t tests and 1-way repeated-measures ANOVA. RESULTS Significant reductions were observed for systolic (-16.6 mmHg) and diastolic (-9.1 mmHg) blood pressure (P < 0.0005), serum lipids (P ≤ 0.008), and total medication usage (P < 0.0005). Other CVD risk factors, including weight (P < 0.0005), waist circumference (P < 0.0005), heart rate (P = 0.018), insulin (P < 0.0005), glycated hemoglobin (P = 0.002), and high-sensitivity C-reactive protein (P = 0.001) were also reduced. CONCLUSION A defined, plant-based diet can be used as an effective therapeutic strategy in the clinical setting to mitigate cardiovascular risk factors and reduce patient drug burden.

Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200-499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study.

Abstract: Despite reducing progression and promoting regression of coronary atherosclerosis, statin therapy does not fully address residual cardiovascular (CV) risk. High-purity eicosapentaenoic acid (EPA) added to a statin has been shown to reduce CV events and induce regression of coronary atherosclerosis in imaging studies; however, data are from Japanese populations without high triglyceride (TG) levels and baseline EPA serum levels greater than those in North American populations. Icosapent ethyl is a high-purity prescription EPA ethyl ester approved at 4 g/d as an adjunct to diet to reduce TG levels in adults with TG levels >499 mg/dL. The objective of the randomized, double-blind, placebo-controlled EVAPORATE study is to evaluate the effects of icosapent ethyl 4 g/d on atherosclerotic plaque in a North American population of statin-treated patients with coronary atherosclerosis, TG levels of 200 to 499 mg/dL, and low-density lipoprotein cholesterol levels of 40 to 115 mg/dL. The primary endpoint is change in low-attenuation plaque volume measured by multidetector computed tomography angiography. Secondary endpoints include incident plaque rates; quantitative changes in different plaque types and morphology; changes in markers of inflammation, lipids, and lipoproteins; and the relationship between these changes and plaque burden and/or plaque vulnerability. Approximately 80 patients will be followed for 9 to 18 months. The clinical implications of icosapent ethyl 4 g/d treatment added to statin therapy on CV endpoints are being evaluated in the large CV outcomes study REDUCE-IT. EVAPORATE will provide important imaging-derived data that may add relevance to the clinically derived outcomes from REDUCE-IT.

Relation between age and carotid artery intima‐medial thickness: a systematic review

Abstract: Carotid artery intima-medial thickness (cIMT) represents a popular measure of atherosclerosis and is predictive of future cardiovascular and cerebrovascular events. Although older age is associated with a higher cIMT, little is known about whether this increase in cIMT follows a linear relationship with age or it is affected under influence of cardiovascular diseases (CVD) or CVD risk factors. We hypothesize that the relationship between cIMT and age is nonlinear and is affected by CVD or risk factors. A systematic review of studies that examined cIMT in the general population and human populations free from CVD/risk factors was undertaken. The literature search was conducted in PubMed, Scopus, and Web of Science. Seventeen studies with 32 unique study populations, involving 10,124 healthy individuals free from CVD risk factors, were included. Furthermore, 58 studies with 115 unique study populations were included, involving 65,774 individuals from the general population (with and without CVD risk factors). A strong positive association was evident between age and cIMT in the healthy population, demonstrating a gradual, linear increase in cIMT that did not differ between age decades (r = 0.91, P < 0.001). Although populations with individuals with CVD demonstrated a higher cIMT compared to populations free of CVD, a linear relation between age and cIMT was also present in this population. Our data suggest that cIMT is strongly and linearly related to age. This linear relationship was not affected by CVD or risk factors.

Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease).

Abstract: The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are increasingly evident. A majority of these patients have coronary microvascular dysfunction. These patients have elevated risk for a cardiovascular event (including acute coronary syndrome, myocardial infarction, stroke, and repeated cardiovascular procedures) and appear to be at higher risk for development of heart failure with preserved ejection fraction. Terminology such as coronary artery disease or coronary heart disease is often synonymous with obstructive atherosclerosis in the clinician's mind, leaving one at a loss to recognize or explain the phenomenon of MINOCA and INOCA with elevated risk. We review the available literature regarding stable and unstable ischemic heart disease that suggests that use of the ischemic heart disease (IHD) terminology matters for women, and should facilitate recognition of risk to provide potential treatment targets and optimized health.

Consumption of a defined, plant-based diet reduces lipoprotein(a), inflammation, and other atherogenic lipoproteins and particles within 4 weeks.

Abstract: BACKGROUND Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein and is minimally effected by lifestyle changes. While some drugs can reduce Lp(a), diet has not consistently shown definitive reduction of this biomarker. The effect of consuming a plant-based diet on serum Lp(a) concentrations have not been previously evaluated. HYPOTHESIS Consumption of a defined, plant-based for 4 weeks reduces Lp(a). METHODS Secondary analysis of a previous trial was conducted, in which overweight and obese individuals (n = 31) with low-density lipoprotein cholesterol concentrations >100 mg/dL consumed a defined, plant-based diet for 4 weeks. Baseline and 4-week labs were collected. Data were analyzed using a paired samples t-test. RESULTS Significant reductions were observed for serum Lp(a) (-32.0 ± 52.3 nmol/L, P = 0.003), apolipoprotein B (-13.2 ± 18.3 mg/dL, P < 0.0005), low-density lipoprotein (LDL) particles (-304.8 ± 363.0 nmol/L, P < 0.0005) and small-dense LDL cholesterol (-10.0 ± 9.2 mg/dL, P < 0.0005). Additionally, serum interleukin-6 (IL-6), total white blood cells, lipoprotein-associated phospholipase A2 (Lp-PLA2), high-sensitivity c-reactive protein (hs-CRP), and fibrinogen were significantly reduced (P ≤ 0.004). CONCLUSIONS A defined, plant-based diet has a favorable impact on Lp(a), inflammatory indicators, and other atherogenic lipoproteins and particles. Lp(a) concentration was previously thought to be only minimally altered by dietary interventions. In this protocol however, a defined plant-based diet was shown to substantially reduce this biomarker. Further investigation is required to elucidate the specific mechanisms that contribute to the reductions in Lp(a) concentrations, which may include alterations in gene expression.

What the Women's Health Initiative has taught us about menopausal hormone therapy.

Abstract: Our understanding of the complex relationship between menopausal hormone therapy (MHT) and cardiovascular disease (CVD) risk has been informed by detailed analyses in the Women's Health Initiative (WHI), the largest randomized, placebo-controlled trial evaluating MHT in postmenopausal women. Although the WHI demonstrated increased risk of CVD events with MHT in the overall cohort, subsequent secondary analyses demonstrated that these risks were influenced by the woman's age and time since menopause, with lower absolute risks and hazard ratios for younger than older women. As MHT is the most effective treatment for the vasomotor symptoms of menopause, it is important to understand its risks and how to conduct risk stratification for symptomatic women. In addition to reviewing the WHI findings, studies pre- and post-WHI are reviewed to describe the relationship between MHT and CVD risk in menopausal women. The absolute risks of adverse cardiovascular events for MHT initiated in women close to menopause are low, and all-cause mortality effects are neutral or even favorable for younger menopausal women. The WHI has advanced and refined our understanding of the relationship between MHT and CVD risk. Although MHT should not be used for CVD prevention, absolute risks of CVD are low when MHT is started close to menopause in healthy women and hazard ratios tend to be lower for younger than older women. For women in early menopause and without contraindications to treatment, the benefits of MHT are likely to outweigh the risks when used for menopausal symptom management.

Lipid profile and incidence of atrial fibrillation: A prospective cohort study in China.

Abstract: BACKGROUND The association between dyslipidemia, a major risk factor for cardiovascular diseases, and atrial fibrillation (AF) is not clear because of limited evidence. HYPOTHESIS Dyslipidemia may be associated with increased risk of AF in a Chinese population. METHODS A total of 88 785 participants free from AF at baseline (2006-2007) were identified from the Kailuan Study. Fasting levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured at baseline using standard procedures. The study population was stratified based on quartiles of lipid profile. Incident AF was ascertained from electrocardiograms at biennial follow-up visits (2008-2015). The associations between incident AF and the different lipid parameters (TC, LDL-C, HDL-C, and TG) were assessed by Cox proportional hazards regression analysis. RESULTS Over a mean follow-up period of 7.12 years, 328 subjects developed AF. Higher TC (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.84) and LDL-C (HR: 0.60, 95% CI: 0.43-0.83) levels were inversely associated with incident AF after multivariable adjustment. HDL-C and TG levels showed no association with newly developed AF. The results remained consistent after exclusion of individuals with myocardial infarction or cerebral infarction, or those on lipid-lowering therapy. Both TC/HDL-C and LDL-C/HDL-C ratios were inversely associated with risk of AF (per unit increment, HR: 0.88, 95% CI: 0.79-0.98 and HR: 0.77, 95% CI: 0.66-0.91, respectively). CONCLUSIONS TC and LDL-C levels were inversely associated with incident AF, whereas no significant association of AF with HDL-C or TG levels was observed.

Hypertension in pregnancy: Taking cues from pathophysiology for clinical practice.

Abstract: Pregnancy-related hypertension (PHTN) syndromes are a frequent and potentially deadly complication of pregnancy, while also negatively impacting the lifelong health of the mother and child. PHTN appears in women likely to develop hypertension later in life, with the stress of pregnancy unmasking a subclinical hypertensive phenotype. However, distinguishing between PHTN and chronic hypertension is essential for optimal management. Preeclampsia (PE) is linked to potentially severe outcomes and lacks effective treatments due to poorly understood mechanisms. Inadequate remodeling of spiral uterine arteries (SUAs), the cornerstone of PE pathophysiology, leads to hypoperfusion of the developing placenta. In normal pregnancies, extravillous trophoblast (EVT) cells assume an invasive phenotype and invade SUAs, transforming them into large conduits. Decidual natural killer cells play an essential role, mediating materno-fetal immune tolerance, inducing early SUA remodeling and regulating EVT invasiveness. Notch signaling is important in EVT phenotypic switch and is dysregulated in PE. The hypoxic placenta releases antiangiogenic and proinflammatory factors that converge upon maternal endothelium, inducing endothelial dysfunction, hypertension, and organ damage. Hypoxia-inducible factor 1-α is upstream of such molecules, whereas endothelin-1 is a major effector. We also describe important genetic links and evidence of incomplete materno-fetal immune tolerance, with PE patients presenting with autoantibodies, lower Treg , and higher Th 17 cells. Thus, PE manifestations arise as a consequence of mal-placentation or/and because of a predisposition of the maternal vascular bed to excessively react to pathogenic molecules. From this pathophysiological basis, we provide current and propose future therapeutic directions for PE.

Sustained sex-based treatment differences in acute coronary syndrome care: Insights from the American Heart Association Get With The Guidelines Coronary Artery Disease Registry.

Abstract: BACKGROUND Sex-based differences in acute coronary syndrome (ACS) mortality may attenuate with age due to better symptom recognition and prompt care. HYPOTHESIS Age is a modifier of temporal trends in sex-based differences in ACS care. METHODS Among 104 817 eligible patients with ACS enrolled in the AHA Get With the Guidelines-Coronary Artery Disease registry between 2003 and 2008, care and in-hospital mortality were evaluated stratified by sex and age. Temporal trends within sex and age groups were assessed for 2 care processes: percentage of STEMI patients presenting to PCI-capable hospitals with a DTB time ≤ 90 minutes (DTB90) and proportion of eligible ACS patients receiving aspirin within 24 hours. RESULTS After adjustment for clinical risk factors and sociodemographic and hospital characteristics, 2276 (51.7%) women and 6276 (56.9%) men with STEMI were treated with DTB90 (adjusted OR: 0.85, 95% CI: 0.80-0.91, P < 0.0001 for women vs men). Time trend analysis showed an absolute increase ranging from 24% to 35% in DTB90 rates among both men and women (P for trend <0.0001 for each group), with consistent differences over time across the 4 age/sex groups (3-way P-interaction = 0.93). Despite high rate of baseline aspirin use (87%-91%), there was a 9% to 11% absolute increase in aspirin use over time, also with consistent differences across the 4 age/sex groups (all 3-way P-interaction ≥0.15). CONCLUSIONS Substantial gains of generally similar magnitude existed in ACS performance measures over 6 years of study across sex and age groups; areas for improvement remain, particularly among younger women.

Suspicious index in Lyme carditis: Systematic review and proposed new risk score.

Abstract: BACKGROUND Lyme carditis (LC), an early manifestation of Lyme disease that most commonly presents as high-degree atrioventricular block (AVB), usually resolves with antibiotic treatment. When LC is not identified as the cause of AVB, a permanent pacemaker may be inappropriately implanted in a reversible cardiac conduction disorder. HYPOTHESIS The likelihood that a patient's high-degree AVB is caused by LC can be evaluated by clinical characteristics incorporated into a risk stratification tool. METHODS A systematic review of all published cases of LC with high-degree AVB, and five cases from the authors' experience, was conducted. The results informed the development of a new risk stratification tool, the Suspicious Index in LC (SILC) score. The SILC score was then applied to each case included in the review. RESULTS Of the 88 cases included, 51 (58%) were high-risk, 31 (35.2%) intermediate-risk, and 6 (6.8%) low-risk for LC according to the SILC score (sensitivity 93.2%). For the subset of 32 cases that reported on all SILC variables, 24 (75%) cases were classified as high-risk, 8 (25%) intermediate-risk, and 0 low-risk (sensitivity 100%). Specificity could not be assessed (no control group). Notably, 6 of the 11 patients who received permanent pacemakers had reversal of AVB with antibiotic treatment. CONCLUSION The SILC risk score and COSTAR mnemonic (constitutional symptoms; outdoor activity; sex = male; tick bite; age < 50; rash = erythema migrans) may help to identify LC in patients presenting with high-degree AVB, and ultimately, minimize the implantation of unnecessary permanent pacemakers.

The connection between the breast and heart in a woman: Breast cancer and cardiovascular disease

Abstract: Cardiovascular disease remains the leading cause of death in women in the United States and is a major public health issue for all women, but it is of increasing concern to breast cancer survivors. Advancements in early detection and breast cancer therapy have resulted in over 90% of women surviving 5 years past their diagnosis of breast cancer. Nonetheless, with increased survivorship from breast cancer, there has been an increase in cardiovascular disease in these women. The consequences of the treatments for breast cancer may increase the risk for cardiovascular disease. Additionally, there is an overlap of risk factors common to both breast cancer and cardiovascular disease. The increased risk of cardiovascular disease in women who survive breast cancer must be recognized, with a focus on the prevention and early detection of cardiovascular disease.

The prevalence of obstructive sleep apnea in patients with atrial fibrillation.

Abstract: Background Obstructive sleep apnea (OSA) is a systemic disorder associated with significant cardiovascular complications. OSA may play a role in the initiation and worsening of atrial fibrillation (AF). This study aimed to determine the prevalence and clinical predictors of OSA in patients with AF. Hypothesis OSA is underdiagnosed in a large number of patients with AF and may not be predicted by conventional clinical indices. Methods Consecutive nonselected patients with AF were recruited from different arrhythmia clinics in Toronto, Ontario, Canada. Patients with previous diagnosis and/or treatment of OSA were excluded. Patients underwent 2 consecutive nights of ambulatory sleep testing with full electroencephalogram recording. OSA was defined as an Apnea-Hypopnea Index (AHI) score ≥ 5 per hour of sleep. Results 123 patients with AF were recruited, with 100 patients included in the final analysis. OSA was detected in 85% of these patients. 27% of patients with normal overall AHI had an increased AHI during rapid eye movement sleep. Only age and male sex were independent predictors of the presence of OSA in these patients. Conclusions OSA is common and often undetected in patients with AF, especially in nonobese and/or female patients. Patients may have a normal overall AHI but an abnormal AHI during rapid eye movement sleep. The clinical relevance and therapeutic implications in this subgroup should be further investigated. The clinical features of OSA are not reliable predictors of OSA in patients with AF. A low threshold for detection of OSA, with sleep studies, in these patients may be merited.

Spontaneous coronary artery dissection in women: What is known and what is yet to be understood.

Abstract: Spontaneous coronary artery dissection is a nonatherosclerotic etiology of acute coronary syndrome, including sudden cardiac death, which frequently affects younger women. This review highlights contemporary knowledge regarding spontaneous coronary artery dissection demographics, prevalence, diagnosis, presentation, and associated conditions and risks, inpatient treatment, major adverse clinical events, and outpatient management decisions.

Rationale and design of the Virginia Commonwealth University–Anakinra Remodeling Trial‐3 (VCU‐ART3): A randomized, placebo‐controlled, double‐blinded, multicenter study

Abstract: There is clear association between the intensity of the acute inflammatory response during acute myocardial infarction (AMI) and adverse prognosis after AMI. Interleukin-1 (IL-1) is a pro-inflammatory cytokine released during AMI and involved in adverse remodeling and heart failure (HF). We describe a study to evaluate the safety and efficacy of IL-1 blockade using an IL-1 receptor antagonist (anakinra) during the acute phase of ST-segment elevation myocardial infarction (STEMI). The Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3; http://www.ClinicalTrials.gov NCT01950299) is a phase 2, multicenter, double-blinded, randomized, placebo-controlled clinical trial comparing anakinra 100 mg once or twice daily vs matching placebo (1:1:1) for 14 days in 99 patients with STEMI. Patients who present to the hospital with STEMI within 12 hours of symptom onset will be eligible for enrollment. Patients will be excluded for a history of HF (functional class III-IV), severe valvular disease, severe kidney disease (stage 4-5), active infection, recent use of immunosuppressive drugs, active malignancy, or chronic autoimmune/auto-inflammatory diseases. We will measure the difference in the area under the curve for C-reactive protein between admission and day 14, separately comparing each of the anakinra groups with the placebo group. The P value will be considered significant if <0.025 to adjust for multiple comparisons. Patients will also be followed for up to 12 months from enrollment to evaluate cardiac remodeling (echocardiography), cardiac function (echocardiography), and major adverse cardiovascular outcomes (cardiovascular death, MI, revascularization, and new onset of HF).

C-reactive protein during and after myocardial infarction in relation to cardiac injury and left ventricular function at follow-up.

Abstract: BACKGROUND Acute myocardial infarction (MI) invokes a large inflammatory response, which contributes to myocardial repair. HYPOTHESIS We investigated whether C-reactive protein (CRP) measured during MI vs at 1 month follow-up improves the prediction of left ventricular (LV) function. METHODS We prospectively enrolled 131 consecutive patients with acute MI and without non-cardiovascular causes of inflammation. We correlated admission and peak levels of CRP during hospitalization and high-sensitivity (hs) CRP at 1 month follow-up with markers of cardiac injury. Clinical follow-up and echocardiography for LV function were performed at a mean of 17 months. RESULTS Median CRP levels were 1.89 mg/L on admission with MI, peaked to 12.10 mg/L during hospitalization and dropped to 1.24 mg/L at 1 month. Although admission CRP levels only weakly correlated with ejection fraction in the acute phase of MI (coefficient -0.164, P = 0.094), peak CRP was significantly related to ejection fraction (coefficient -0.4, P < 0.001), hsTroponin T (0.389, P < 0.001), and white blood cell count (0.389, P < 0.001). hsCRP at 1 month was not related to the extent of acute cardiac injury. These findings were replicated in an independent cohort of 57 patients. Peak CRP predicted LV dysfunction at follow-up (OR 11.0, 3.1-39.5 per log CRP, P < 0.001), persisting after adjustment for infarct size (OR 5.1, 1.1-23.6, P = 0.037), while hsCRP at 1 month was unrelated to LV function at follow-up. CONCLUSIONS hsCRP 1 month post-MI does not relate to acute cardiac injury or LV function at follow-up, but we confirm that peak CRP is an independent predictor of LV dysfunction at follow-up.

Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis.

Abstract: BACKGROUND Elevated lipoprotein(a) (Lp[a]) and familial hypercholesterolemia (FH) are inherited lipid disorders. Their frequencies, coexistence, and associations with premature coronary artery disease (CAD) in patients admitted to the coronary care unit (CCU) remain to be defined. HYPOTHESIS Elevated Lp(a) and FH are commonly encountered among CCU patients and independently associated with increased premature CAD risk. METHODS Plasma Lp(a) concentrations were measured in consecutive patients admitted to the CCU with an acute coronary syndrome (ACS) or prior history of CAD for 6.5 months. Elevated Lp(a) was defined as concentrations ≥0.5 g/L. Patients with LDL-C ≥ 5 mmol/L exhibited phenotypic FH. Premature CAD was diagnosed in those age < 60 years, and the relationship between this and elevated Lp(a) and FH was determined by logistic regression. RESULTS 316 patients were screened; 163 (51.6%) had premature CAD. Overall, elevated Lp(a) and FH were identified in 27.0% and 11.6% of patients, respectively. Both disorders were detected in 4.4% of individuals. Elevated Lp(a) (32.0% vs 22.2%; P = 0.019) and FH phenotype (15.5% vs 8.0%; P = 0.052) were more common with premature vs nonpremature CAD. Elevated Lp(a) alone conferred a 1.9-fold, FH alone a 3.2-fold, and the combination a 5.3-fold increased risk of premature CAD (P = 0.005). CONCLUSIONS Elevated Lp(a) and phenotypic FH were commonly encountered and more frequent with premature CAD. The combination of both disorders is especially associated with increased CAD risk. Patients admitted to the CCU with ACS or previously documented CAD should be routinely screened for elevated Lp(a) and FH.

Atrial remodeling and ectopic burden in recreational athletes: Implications for risk of atrial fibrillation.

Abstract: Background Atrial remodeling, vagal tone, and atrial ectopic triggers are suggested to contribute to increased incidence of atrial fibrillation (AF) in endurance athletes. How these parameters change with increased lifetime training hours is debated. Hypothesis Atrial remodeling occurs in proportion to total training history, thus contributing to elevated risk of AF. Methods We recruited 99 recreational endurance athletes, subsequently grouped according to lifetime training hours, to undergo evaluation of atrial size, autonomic modulation, and atrial ectopy. Athletes were grouped by self-reported lifetime training hours: low ( 6000 h). Left atrial (LA) volume, left ventricular (LV) dimensions, and LV systolic and diastolic function were assessed by echocardiography. We used 48-hour ambulatory electrocardiographic monitoring to determine heart rate, heart rate variability, premature atrial contractions, and premature ventricular contractions. Results LA volume was significantly greater in the high (+5.1 mL/m2 , 95% CI: 1.3-8.9) and medium (+4.2 mL/m2 , 95% CI: 0.2-8.1) groups, compared with the low group. LA dilation was observed in 19.4%, 12.9%, and 0% of the high, medium, and low groups, respectively (P = 0.05). No differences were observed between groups for measures of LV dimensions or function. Minimum heart rate, parasympathetic tone expressed using heart rate variability indices, and premature atrial contraction and premature ventricular contraction frequencies did not differ between groups. Conclusions In recreational endurance athletes, increased lifetime training is associated with LA dilation in the absence of increased vagal parameters or atrial ectopy, which may promote incidence of AF in this cohort.

A review of factors associated with maintenance of sinus rhythm after elective electrical cardioversion for atrial fibrillation.

Abstract: Atrial fibrillation is the most common heart-rhythm disorder, affecting about 1.5% to 2% of the population with an increased risk of mortality and morbidity due to stroke, thromboembolism, and heart failure. If the conversion back to sinus rhythm does not happen spontaneously, pharmacological or electrical cardioversion (ECV) is the next available treatment options for some patients. However, the long-term success following ECV is variable. This review describes the factors that are associated with maintenance of sinus rhythm following ECV and proposes a clinical strategy based on the available evidence.

The evolving view of coronary artery calcium and cardiovascular disease risk.

Abstract: Calcification of the coronary artery is a complex pathophysiologic process that is intimately associated with atherosclerosis. Extensive investigation has demonstrated the value of identifying and quantifying coronary artery calcium (CAC) in atherosclerotic cardiovascular disease (CVD) prognostication. However, over the last several years, an increasing body of evidence has suggested that CAC has underappreciated aspects that modulate, and at times attenuate, future CVD risk. The most commonly used measure of CAC, the Agatston unit, effectively models both higher density and higher area of CAC as risk factors for future CVD events. Recent findings from the Multi-Ethnic Study of Atherosclerosis (MESA) have challenged this assumption, demonstrating that higher density of CAC is protective for coronary heart disease and CVD events. Statins may be associated with an increase in CAC, an unexpected finding given their clear benefits in the prevention and treatment of CVD. Studies utilizing intracoronary ultrasound and coronary computed tomography angiography have demonstrated that calcified atherosclerotic plaque-as compared with noncalcified or sparsely calcified plaque-is associated with fewer CVD events. These studies lend support to the often-asserted (but as yet unvalidated) view that calcification may play a role in plaque stabilization. Furthermore, vascular calcification, though a surrogate for atherosclerotic plaque burden, may also possess identifiable aspects that can refine CVD risk assessment.

Atrial fibrillation patient preferences for oral anticoagulation and stroke knowledge: Results of a conjoint analysis.

Abstract: Background Guidelines recommend that patients with atrial fibrillation (AF) are involved in oral anticoagulant (OAC) treatment decisions. Understanding which OAC attributes AF patients value most could help optimize treatment. Objective To assess the relationship between patient's stroke knowledge and their preferences for specific OAC attributes. Methods A cross-sectional online survey was conducted in patients with nonvalvular AF taking an OAC for stroke prevention in the United States, Canada, Germany, France, and Japan. Patients were asked about their stroke knowledge, perception of the seriousness of AF and concern about stroke, and to rank 7 OAC attributes in order of importance. A conjoint analysis was performed to determine the inherent value of 4 attributes. Results In total, 937 patients (mean age [standard deviation] 54.3 [16.6] years; 37.1% female) participated. Of these, 19.5%, 27.9%, and 29.8% had good, moderate, and low stroke knowledge, respectively; 22.8% had no stroke knowledge. Overall, 39.4% of patients (47.5% with good stroke knowledge) perceived AF as very/extremely serious. The OAC attribute ranked as most important was stroke prevention followed by major bleeding risk, other side effects, dosing frequency, antidote availability, dietary restrictions, and use with/without food. In the conjoint analysis, stroke risk reduction was the most valued property, followed by reduction in major bleeding risk, less frequent administration, and administration with/without food. Preferences did not differ with level of stroke knowledge, perception of seriousness of AF, concern of stroke, or medication burden. Conclusions Most AF patients consider efficacy and safety to be the most important OAC attributes, whereas dosing frequency was deemed as less important.

Effect of body mass index on survival after sudden cardiac arrest

Abstract: BACKGROUND Although elevated body mass index (BMI) is a risk factor for cardiac disease, patients with elevated BMI have better survival in the context of severe illness, a phenomenon termed the "obesity paradox." HYPOTHESIS Higher BMI is associated with lower mortality in sudden cardiac arrest (SCA) survivors. METHODS Data were collected on 1433 post-SCA patients, discharged alive from the hospitals of the University of Pittsburgh Medical Center between 2002 and 2012. Of those, 1298 patients with documented BMI during the index hospitalization and follow-up data constituted the study cohort. RESULTS In the overall cohort, 30 patients were underweight (BMI <18.5 kg/m2 ), 312 had normal weight (BMI 18.5-24.9 kg/m2 ), 417 were overweight (BMI 25.0-29.9 kg/m2 ), and 539 were obese (BMI ≥30 kg/m2 ). As expected, the prevalence of coronary artery disease, myocardial infarction, diabetes mellitus, and hypertension increased significantly with increasing BMI. Over a median follow-up of 3.6 years, 602 (46%) patients died. Despite higher prevalence of cardiovascular comorbidities in more obese patients, a higher BMI was associated with lower all-cause mortality on univariate analysis (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.78-0.94, P = 0.002) and multivariate analysis after adjusting for unbalanced baseline comorbidities (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.77-0.96, P = 0.009). CONCLUSIONS Higher BMI is associated with lower all-cause mortality in survivors of SCA, suggesting that the obesity paradox applies to the post-arrest population. Further investigation into its mechanisms may inform the management of post-SCA patients.

How do we attract and retain women in cardiology

Abstract: The recruitment and advancement of women in cardiology is an important priority for the cardiology community. Despite improvements in sex disparities over the last 2 decades, women remain a small minority in cardiology. Recent studies have revealed key obstacles facing female cardiologists including radiation exposure, family responsibilities, unequal financial compensations, and lack of career advancement. To attract and retain more women into the field of cardiology, the cardiology community, including professional society leaders, division chiefs, and program directors, must all work to overcome these barriers.

Stem-cell therapy in ST-segment elevation myocardial infarction with reduced ejection fraction: A multicenter, double-blind randomized trial.

Abstract: Background Left ventricular ejection fraction (LVEF) is a major determinant of long-term prognosis after ST-segment elevation myocardial infarction (STEMI). STEMI patients with reduced LVEF have a poor prognosis, despite successful reperfusion and the use of renin-angiotensin-aldosterone inhibitors. Hypothesis Intracoronary infusion of bone marrow-derived mononuclear cells (BMMC) may improve LVEF in STEMI patients successfully reperfused. Methods The main inclusion criteria for this double-blind, randomized, multicenter study were patient age 30 to 80 years, LVEF ≤50%, successful angioplasty of infarct-related artery, and regional dysfunction in the infarct-related area analyzed before cell injection. Cardiac magnetic resonance imaging was used to assess LVEF, left ventricular volumes, and infarct size at 7 to 9 days and 6 months post-myocardial infarction. Results One hundred and twenty-one patients were included (66 patients in the BMMC group and 55 patients in the placebo group). The primary endpoint, mean LVEF, was similar between both groups at baseline (44.63% ± 10.74% vs 42.23% ± 10.33%; P = 0.21) and at 6 months (44.74% ± 12.95 % vs 43.50 ± 12.43%; P = 0.59). The groups were also similar regarding the difference between baseline and 6 months (0.11% ± 8.5% vs 1.27% ± 8.93%; P = 0.46). Other parameters of left ventricular remodeling, such as systolic and diastolic volumes, as well as infarct size, were also similar between groups. Conclusions In this randomized, multicenter, double-blind trial, BMMC intracoronary infusion did not improve left ventricular remodeling or decrease infarct size.

Subvalvular aortic stenosis: a review of current literature.

Abstract: Subvalvular aortic stenosis (SAS) is one of the common adult congenital heart diseases, with a prevalence of 6.5%. It is usually diagnosed in the first decade of life. Echocardiography is the test of choice to diagnose SAS. Surgical correction is the best treatment modality, and the prognosis is usually excellent. In this review, we describe the pathophysiology, diagnosis, prognosis, and management of SAS with a focus on different pathophysiologic mechanisms, diagnostic approach, and prognosis of the disease by reviewing the current literature.

Harnessing mHealth technologies to increase physical activity and prevent cardiovascular disease.

Abstract: Research into prevention of cardiovascular disease has increasingly focused on mobile health (mHealth) technologies and their efficacy in helping individuals adhere to heart-healthy recommendations, including daily physical activity levels. By including the use of mHealth technologies in the discussion of physical activity recommendations, clinicians empower patients to play an active daily role in modifying their cardiovascular risk-factor profile. In this review, we critically evaluate the mHealth and physical activity literature to determine how these tools may lower cardiovascular risk while providing real-time tracking, feedback, and motivation on physical activity levels. We analyze the various domains-including user knowledge, social support, behavioral change theory, and self-motivation-that potentially influence the effectiveness of smartphone applications to impact individual physical activity levels. In doing so, we hope to provide a thorough overview of the mHealth landscape, in addition to highlighting many of the administrative, reimbursement, and patient-privacy challenges of using these technologies in patient care. Finally, we propose a behavioral change model and checklist for clinicians to assist patients in utilizing mHealth technology to best achieve meaningful changes in daily physical activity levels.

Early effects of empagliflozin on exercise tolerance in patients with heart failure: A pilot study

Abstract: BACKGROUND Sodium-glucose linked transporter 2 inhibition recently emerged as a promising therapy for reducing the risk of heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). However, there is a lack of data endorsing its role in symptomatic HF patients. We sought to evaluate the short-term effects of empagliflozin on maximal exercise capacity in these patients. HYPOTHESIS We postulate tretament with empagliflozin may improve functional capacity in patients with T2DM and established HF. METHODS Nineteen T2DM patients with symptomatic HF were prospectively included and underwent cardiopulmonary exercise testing before and 30 days after initiation of empagliflozin therapy. A mixed-effects model for repeated measures was used. RESULTS Median patient age was 72 years (interquartile range, 60-79 years); 42.1% were in New York Heart Association class III. Baseline mean (± SD) peak oxygen consumption (peak VO2 ) was 10.9 ± 4.0 mL/min/kg. Peak VO2 increased significantly at 30 days (∆: +1.21 [0.66 to 1.76] mL/min/kg; P < 0.001). A significant improvement in ventilatory efficiency during exercise, 6-minute walking distance, and quality of life, and a reduction in antigen carbohydrate 125, were also found. Estimated glomerular filtration rate and natriuretic peptides did not significantly change. CONCLUSIONS In this pilot study, empagliflozin was associated with 1-month improvement in exercise capacity in T2DM patients with symptomatic HF. This beneficial effect was also found for other surrogates of severity.

Does obesity affect the outcomes in takotsubo cardiomyopathy? Analysis of the Nationwide Inpatient Sample database, 2010-2014.

Abstract: BACKGROUND Obesity can lead to increased oxidative stress which is one of the proposed mechanisms in the etiopathogenesis of takotsubo cardiomyopathy (TCM). HYPOTHESIS The presence of obesity adversely impacts clinical outcomes in TCM patients. METHODS We queried the Nationwide Inpatient Sample database (2010-2014) to identify adult patients admitted with a principal diagnosis of TCM with and without obesity. We compared the categorical and continuous variables by Pearson χ2 and Student t test, respectively, in propensity-score matched cohorts. RESULTS The study cohort comprised 612 obese TCM (weighted n = 3034) and 5696 nonobese TCM (weighted n = 28 186) patients. Obese TCM patients were more often younger and private-insurance enrollees. Cardiac complications including acute myocardial infarction (9.0% vs 7.4%; P = 0.04), cardiac arrest (2.3% vs. 0.4%; P < 0.001), cardiogenic shock (4.3% vs. 3.2%; P = 0.03), congestive heart failure (5.0% vs. 3.8%; P = 0.02), respiratory failure (12.9% vs. 11.0%; P = 0.021) and use of mechanical hemodynamic support (Impella; 0.2% vs. 0.0%, P = 0.02) were significantly higher among obese TCM patients. There were no significant differences between the 2 groups in all-cause mortality (1.0% vs. 0.8%; P = 0.35), arrhythmia (24.5% vs. 22.7%, P = 0.123), length of stay (3.7 ±3.5 vs. 3.7 ±3.6 days; P = 0.68), and total hospital charges ($40 780.16 vs. $42 575.14; P = 0.08). CONCLUSIONS Obese TCM patients were more susceptible to developing TCM-related cardiac complications than were nonobese TCM patients, without any impact on all-cause in-hospital mortality, LOS, and hospital charges.