Browsing by Author "Velazquez, Eric J"

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Open Access
Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact.
(J Card Fail, 2015-09) Buggey, Jonathan; Mentz, Robert J; DeVore, Adam D; Velazquez, Eric J
Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity over the past decade of new pharmacotherapies that improve outcomes. However, recent data from a large randomized controlled trial compared the novel agent LCZ696, a dual-acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well established angiotensin-converting enzyme (ACE) inhibitor enalapril and found significant reduction in mortality among the chronic reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides and thereby promoting natriuresis and vasodilatation and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACE inhibition but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNi LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest that LCZ696 may improve surrogate markers of HF severity. In this paper, we review the preclinical and clinical data that led to the development of LCZ696, the understanding of the underlying mechanistic action, and the robust clinical impact that LCZ696 may have in the near future.
Open Access
Blood pressure level impacts risk of death among HIV seropositive adults in Kenya: a retrospective analysis of electronic health records.
(BMC Infect Dis, 2014-05-22) Bloomfield, Gerald S; Hogan, Joseph W; Keter, Alfred; Holland, Thomas L; Sang, Edwin; Kimaiyo, Sylvester; Velazquez, Eric J
BACKGROUND: Mortality among people with human immunodeficiency virus (HIV) infection is increasingly due to non-communicable causes. This has been observed mostly in developed countries and the routine care of HIV infected individuals has now expanded to include attention to cardiovascular risk factors. Cardiovascular risk factors such as high blood pressure are often overlooked among HIV seropositive (+) individuals in sub-Saharan Africa. We aimed to determine the effect of blood pressure on mortality among HIV+ adults in Kenya. METHODS: We performed a retrospective analysis of electronic medical records of a large HIV treatment program in western Kenya between 2005 and 2010. All included individuals were HIV+. We excluded participants with AIDS, who were <16 or >80 years old, or had data out of acceptable ranges. Missing data for key covariates was addressed by inverse probability weighting. Primary outcome measures were crude mortality rate and mortality hazard ratio (HR) using Cox proportional hazards models adjusted for potential confounders including HIV stage. RESULTS: There were 49,475 (74% women) HIV+ individuals who met inclusion and exclusion criteria. Mortality rates for men and women were 3.8 and 1.8/100 person-years, respectively, and highest among those with the lowest blood pressures. Low blood pressure was associated with the highest mortality incidence rate (IR) (systolic <100 mmHg IR 5.2 [4.8-5.7]; diastolic <60 mmHg IR 9.2 [8.3-10.2]). Mortality rate among men with high systolic blood pressure without advanced HIV (3.0, 95% CI: 1.6-5.5) was higher than men with normal systolic blood pressure (1.1, 95% CI: 0.7-1.7). In weighted proportional hazards regression models, men without advanced HIV disease and systolic blood pressure ≥140 mmHg carried a higher mortality risk than normotensive men (HR: 2.39, 95% CI: 0.94-6.08). CONCLUSIONS: Although there has been little attention paid to high blood pressure among HIV+ Africans, we show that blood pressure level among HIV+ patients in Kenya is related to mortality. Low blood pressure carries the highest mortality risk. High systolic blood pressure is associated with mortality among patients whose disease is not advanced. Further investigation is needed into the cause of death for such patients.
Open Access
CABG or PCI for Diabetic Patients With Left Ventricular Dysfunction: Closing in on the Truth?
(Journal of the American College of Cardiology, 2018-02) Velazquez, Eric J; Petrie, Mark C
Open Access
Clinical and echocardiographic predictors of mortality in acute pulmonary embolism.
(Cardiovasc Ultrasound, 2016-10-28) Dahhan, Talal; Siddiqui, Irfan; Tapson, Victor F; Velazquez, Eric J; Sun, Stephanie; Davenport, Clemontina A; Samad, Zainab; Rajagopal, Sudarshan
PURPOSE: The aim of this study was to evaluate the utility of adding quantitative assessments of cardiac function from echocardiography to clinical factors in predicting the outcome of patients with acute pulmonary embolism (PE). METHODS: Patients with a diagnosis of acute PE, based on a positive ventilation perfusion scan or computed tomography (CT) chest angiogram, were identified using the Duke University Hospital Database. Of these, 69 had echocardiograms within 24-48 h of the diagnosis that were suitable for offline analysis. Clinical features that were analyzed included age, gender, body mass index, vital signs and comorbidities. Echocardiographic parameters that were analyzed included left ventricular (LV) ejection fraction (EF), regional, free wall and global RV speckle-tracking strain, RV fraction area change (RVFAC), Tricuspid Annular Plane Systolic Excursion (TAPSE), pulmonary artery acceleration time (PAAT) and RV myocardial performance (Tei) index. Univariable and multivariable regression statistical analysis models were used. RESULTS: Out of 69 patients with acute PE, the median age was 55 and 48 % were female. The median body mass index (BMI) was 27 kg/m(2). Twenty-nine percent of the cohort had a history of cancer, with a significant increase in cancer prevalence in non-survivors (57 % vs 29 %, p = 0.02). Clinical parameters including heart rate, respiratory rate, troponin T level, active malignancy, hypertension and COPD were higher among non-survivors when compared to survivors (p ≤ 0.05). Using univariable analysis, NYHA class III symptoms, hypoxemia on presentation, tachycardia, tachypnea, elevation in Troponin T, absence of hypertension, active malignancy and chronic obstructive pulmonary disease (COPD) were increased in non-survivors compared to survivors (p ≤ 0.05). In multivariable models, RV Tei Index, global and free (lateral) wall RVLS were found to be negatively associated with survival probability after adjusting for age, gender and systolic blood pressure (p ≤ 0.05). CONCLUSION: The addition of echocardiographic assessment of RV function to clinical parameters improved the prediction of outcomes for patients with acute PE. Larger studies are needed to validate these findings.
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Clinical characteristics and 12-month outcomes of patients with valvular and non-valvular atrial fibrillation in Kenya.
(PLoS One, 2017) Temu, Tecla M; Lane, Kathleen A; Shen, Changyu; Ng'ang'a, Loise; Akwanalo, Constantine O; Chen, Peng-Sheng; Emonyi, Wilfred; Heckbert, Susan R; Koech, Myra M; Manji, Imran; Vatta, Matteo; Velazquez, Eric J; Wessel, Jennifer; Kimaiyo, Sylvester; Inui, Thomas S; Bloomfield, Gerald S
BACKGROUND: Atrial fibrillation (AF) is a major contributor to the global cardiovascular disease burden. The clinical profile and outcomes of AF patients with valvular heart diseases in sub-Saharan Africa (SSA) have not been adequately described. We assessed clinical features and 12-month outcomes of patients with valvular AF (vAF) in comparison to AF patients without valvular heart disease (nvAF) in western Kenya. METHODS: We performed a cohort study with retrospective data gathering to characterize risk factors and prospective data collection to characterize their hospitalization, stroke and mortality rates. RESULTS: The AF patients included 77 with vAF and 69 with nvAF. The mean (SD) age of vAF and nvAF patients were 37.9(14.5) and 69.4(12.3) years, respectively. There were significant differences (p<0.001) between vAF and nvAF patients with respect to female sex (78% vs. 55%), rates of hypertension (29% vs. 73%) and heart failure (10% vs. 49%). vAF patients were more likely to be taking anticoagulation therapy compared to those with nvAF (97% vs. 76%; p<0.01). After 12-months of follow-up, the overall mortality, hospitalization and stroke rates for vAF patients were high, at 10%, 34% and 5% respectively, and were similar to the rates in the nvAF patients (15%, 36%, and 5%, respectively). CONCLUSION: Despite younger age and few comorbid conditions, patients with vAF in this developing country setting are at high risk for nonfatal and fatal outcomes, and are in need of interventions to improve short and long-term outcomes.
Open Access
Factors associated with isolated right heart failure in women: a pilot study from western Kenya.
(Glob Heart, 2014-06) Lagat, David K; DeLong, Allison K; Wellenius, Gregory A; Carter, E Jane; Bloomfield, Gerald S; Velazquez, Eric J; Hogan, Joseph; Kimaiyo, Sylvester; Sherman, Charles B
BACKGROUND: Small observational studies have found that isolated right heart failure (IRHF) is prevalent among women of sub-Saharan Africa. Further, several risk factors for the development of IRHF have been identified. However, no similar studies have been conducted in Kenya. OBJECTIVE: We hypothesized that specific environmental exposures and comorbidities were associated with IRHF in women of western Kenya. METHODS: We conducted a case-control study at a referral hospital in western Kenya. Cases were defined as women at least 35 years old with IRHF. Control subjects were similarly aged volunteers without IRHF. Exclusion criteria in both groups included history of tobacco use, tuberculosis, or thromboembolic disease. Participants underwent echocardiography, spirometry, 6-min walk test, rest/exercise oximetry, respiratory health interviews, and human immunodeficiency virus (HIV) testing. Home visits were performed to evaluate kitchen ventilation, fuel use, and cook smoke exposure time, all surrogate measures of indoor air pollution (IAP). A total of 31 cases and 65 control subjects were enrolled. Surrogate measures of indoor air pollution were not associated with IRHF. However, lower forced expiratory volume at 1 s percent predicted (adjusted odds ratio [AOR]: 2.02, 95% confidence interval [CI]: 1.27 to 3.20; p = 0.004), HIV positivity (AOR: 40.4, 95% CI: 3.7 to 441; p < 0.01), and self-report of exposure to occupational dust (AOR: 3.9, 95% CI: 1.14 to 14.2; p = 0.04) were associated with IRHF. In an analysis of subgroups of participants with and without these factors, lower kitchen ventilation was significantly associated with IRHF among participants without airflow limitation (AOR: 2.63 per 0.10 unit lower ventilation, 95% CI: 1.06 to 6.49; p = 0.04), without HIV (AOR: 2.55, 95% CI: 1.21 to 5.37; p = 0.02), and without occupational dust exposure (AOR: 2.37, 95% CI: 1.01 to 5.56; p = 0.05). CONCLUSIONS: In this pilot study among women of western Kenya, lower kitchen ventilation, airflow limitation, HIV, and occupational dust exposure were associated with IRHF, overall or in participant subgroups. Direct or indirect causality requires further study.
Open Access
Heart failure in sub-Saharan Africa.
(Curr Cardiol Rev, 2013-05) Bloomfield, Gerald S; Barasa, Felix A; Doll, Jacob A; Velazquez, Eric J
The heart failure syndrome has been recognized as a significant contributor to cardiovascular disease burden in sub-Saharan African for many decades. Seminal knowledge regarding heart failure in the region came from case reports and case series of the early 20th century which identified infectious, nutritional and idiopathic causes as the most common. With increasing urbanization, changes in lifestyle habits, and ageing of the population, the spectrum of causes of HF has also expanded resulting in a significant burden of both communicable and non-communicable etiologies. Heart failure in sub-Saharan Africa is notable for the range of etiologies that concurrently exist as well as the healthcare environment marked by limited resources, weak national healthcare systems and a paucity of national level data on disease trends. With the recent publication of the first and largest multinational prospective registry of acute heart failure in sub-Saharan Africa, it is timely to review the state of knowledge to date and describe the myriad forms of heart failure in the region. This review discusses several forms of heart failure that are common in sub-Saharan Africa (e.g., rheumatic heart disease, hypertensive heart disease, pericardial disease, various dilated cardiomyopathies, HIV cardiomyopathy, hypertrophic cardiomyopathy, endomyocardial fibrosis, ischemic heart disease, cor pulmonale) and presents each form with regard to epidemiology, natural history, clinical characteristics, diagnostic considerations and therapies. Areas and approaches to fill the remaining gaps in knowledge are also offered herein highlighting the need for research that is driven by regional disease burden and needs.
Open Access
Hypertension and Obesity as Cardiovascular Risk Factors among HIV Seropositive Patients in Western Kenya
(2011) Bloomfield, Gerald S; Hogan, Joseph W; Keter, Alfred; Sang, Edwin; Carter, E Jane; Velazquez, Eric J; Kimaiyo, Sylvester
Background--There is increased risk of cardiovascular disease among HIV seropositive individuals. The prevalence of HIV is highest in sub-Saharan Africa; however, HIV-related cardiovascular risk research is largely derived from developed country settings. Herein, we describe the prevalence of hypertension and obesity in a large HIV treatment program in Kenya. Methods--We performed a retrospective analysis of the electronic medical records of a large HIV treatment program in Western Kenya between 2006 and 2009. We calculated the prevalence of hypertension and obesity among HIV+ adults as well as utilized multiple logistic regression analyses to examine the relationship between clinical characteristics, HIV-related characteristics, and hypertension. Results--Our final sample size was 12,194. The median systolic/diastolic blood pressures were similar for both sexes (male: 110/70 mmHg, female: 110/70 mmHg). The prevalence of hypertension among men and women were 11.2% and 7.4%, respectively. Eleven percent of men and 22.6% of women were overweight/obese (body mass index ≥25 kg/m2). Ordinal logistic regression analyses showed that overweight/obesity was more strongly associated with hypertension among HIV+ men (OR 2.41, 95% CI 1.88–3.09) than a higher successive age category (OR 1.62, 95% CI 1.40–1.87 comparing 16–35, 36–45 and >45 years categories). Among women, higher age category and overweight/obesity were most strongly associated with hypertension (age category: OR 2.21, 95% CI 1.95–2.50, overweight/obesity: OR 1.80, 95% CI 1.50–2.16). Length of time on protease inhibitors was not found to be related to hypertension for men (OR 1.62, 95% CI 0.42–6.20) or women (OR 1.17, 95% CI 0.37–2.65) after adjustment for CD4 count, age and BMI. Conclusion--In Western Kenya, there is a high prevalence of hypertension and overweight/obesity among HIV+ patients with differences observed between men and women. The care of HIV+ patients in sub-Saharan Africa should also include both identification and management of associated cardiovascular risk factors.
Open Access
Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography Laboratory: Improving Care for Patients With Aortic Stenosis.
(Circ Cardiovasc Imaging, 2016-03) Samad, Zainab; Minter, Stephanie; Armour, Alicia; Tinnemore, Amanda; Sivak, Joseph A; Sedberry, Brenda; Strub, Karen; Horan, Seanna M; Harrison, J Kevin; Kisslo, Joseph; Douglas, Pamela S; Velazquez, Eric J
BACKGROUND: The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. METHODS AND RESULTS: The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography-catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). CONCLUSIONS: A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.
Open Access
Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.
(J Am Heart Assoc, 2016-07-29) Hunter, Wynn G; Kelly, Jacob P; McGarrah, Robert W; Khouri, Michel G; Craig, Damian; Haynes, Carol; Ilkayeva, Olga; Stevens, Robert D; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Felker, G Michael; Hernandez, Adrian F; Velazquez, Eric J; Kraus, William E; Shah, Svati H
BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No-HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long-chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no-HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance. CONCLUSIONS: We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.
Open Access
Mobile health for non-communicable diseases in Sub-Saharan Africa: a systematic review of the literature and strategic framework for research.
(Global Health, 2014-06-13) Bloomfield, Gerald S; Vedanthan, Rajesh; Vasudevan, Lavanya; Kithei, Anne; Were, Martin; Velazquez, Eric J
BACKGROUND: Mobile health (mHealth) approaches for non-communicable disease (NCD) care seem particularly applicable to sub-Saharan Africa given the penetration of mobile phones in the region. The evidence to support its implementation has not been critically reviewed. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane Central Register of Clinical Trials, a number of other databases, and grey literature for studies reported between 1992 and 2012 published in English or with an English abstract available. We extracted data using a standard form in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Our search yielded 475 citations of which eleven were reviewed in full after applying exclusion criteria. Five of those studies met the inclusion criteria of using a mobile phone for non-communicable disease care in sub-Saharan Africa. Most studies lacked comparator arms, clinical endpoints, or were of short duration. mHealth for NCDs in sub-Saharan Africa appears feasible for follow-up and retention of patients, can support peer support networks, and uses a variety of mHealth modalities. Whether mHealth is associated with any adverse effect has not been systematically studied. Only a small number of mHealth strategies for NCDs have been studied in sub-Saharan Africa. CONCLUSIONS: There is insufficient evidence to support the effectiveness of mHealth for NCD care in sub-Saharan Africa. We present a framework for cataloging evidence on mHealth strategies that incorporates health system challenges and stages of NCD care. This framework can guide approaches to fill evidence gaps in this area. Systematic review registration: PROSPERO CRD42014007527.
Open Access
Optimizing linkage and retention to hypertension care in rural Kenya (LARK hypertension study): study protocol for a randomized controlled trial.
(Trials, 2014-04-27) Vedanthan, Rajesh; Kamano, Jemima H; Naanyu, Violet; Delong, Allison K; Were, Martin C; Finkelstein, Eric A; Menya, Diana; Akwanalo, Constantine O; Bloomfield, Gerald S; Binanay, Cynthia A; Velazquez, Eric J; Hogan, Joseph W; Horowitz, Carol R; Inui, Thomas S; Kimaiyo, Sylvester; Fuster, Valentin
BACKGROUND: Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and delays in seeking care are associated with increased mortality. Thus, a critical component of hypertension management is to optimize linkage and retention to care. METHODS/DESIGN: This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive individuals to a hypertension care program and significantly reduce blood pressure among them. The study will be conducted in the Kosirai and Turbo Divisions of western Kenya. An initial phase of qualitative inquiry will assess facilitators and barriers of linkage and retention to care using a modified Health Belief Model as a conceptual framework. Subsequently, we will conduct a cluster randomized controlled trial with three arms: 1) usual care (community health workers with the standard level of hypertension care training); 2) community health workers with an additional tailored behavioral communication strategy; and 3) community health workers with a tailored behavioral communication strategy who are also equipped with smartphone technology. The co-primary outcome measures are: 1) linkage to hypertension care, and 2) one-year change in systolic blood pressure among hypertensive individuals. Cost-effectiveness analysis will be conducted in terms of costs per unit decrease in blood pressure and costs per disability-adjusted life year gained. DISCUSSION: This study will provide evidence regarding the effectiveness and cost-effectiveness of strategies to optimize linkage and retention to hypertension care that can be applicable to non-communicable disease management in low- and middle-income countries. TRIAL REGISTRATION: This trial is registered with (NCT01844596) on 30 April 2013.
Open Access
Percutaneous coronary intervention outcomes in patients with stable coronary disease and left ventricular systolic dysfunction.
(ESC heart failure, 2019-12) DeVore, Adam D; Yow, Eric; Krucoff, Mitchell W; Sherwood, Matthew W; Shaw, Linda K; Chiswell, Karen; O'Connor, Christopher M; Ohman, Erik Magnus; Velazquez, Eric J
AIMS:We sought to better understand the role of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) and moderate or severe left ventricular systolic dysfunction. METHODS AND RESULTS:Using data from the Duke Databank for Cardiovascular Disease, we analysed patients who underwent coronary angiography at Duke University Medical Center (1995-2012) that had stable CAD amenable to PCI and left ventricular ejection fraction ≤35%. Patients with acute coronary syndrome or Canadian Cardiovascular Society class III or IV angina were excluded. We used propensity-matched Cox proportional hazards to evaluate the association of PCI with mortality and hospitalizations. Of 901 patients, 259 were treated with PCI and 642 with medical therapy. PCI propensity scores created from 24 variables were used to assemble a matched cohort of 444 patients (222 pairs) receiving PCI or medical therapy alone. Over a median follow-up of 7 years, 128 (58%) PCI and 125 (56%) medical therapy alone patients died [hazard ratio 0.87 (95% confidence interval 0.68, 1.10)]; there was also no difference in the rate of a composite endpoint of all-cause mortality or cardiovascular hospitalization [hazard ratio 1.18 (95% confidence interval 0.96, 1.44)] between the two groups. CONCLUSIONS:In this well-profiled, propensity-matched cohort of patients with stable CAD amenable to PCI and moderate or severe left ventricular systolic dysfunction, the addition of PCI to medical therapy did not improve long-term mortality, or the composite of mortality or cardiovascular hospitalization. The impact of PCI on other outcomes in these high-risk patients requires further study.
Open Access
Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study.
(Am Heart J, 2015-04) Jiang, Wei; Boyle, Stephen H; Ortel, Thomas L; Samad, Zainab; Velazquez, Eric J; Harrison, Robert W; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B; O'Connor, Christopher M; Becker, Richard C
BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS: Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS: Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation , 43.33% (n=117) met criteria for MSIMI and 18.15% (n=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10μM (6.95[5.54] vs. -14.23[8.75].; P=0.045), epinephrine 10μM (12.84[4.84] vs. -6.40[7.61].; P=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. -27.34[8.34]; P<.001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS: These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD.
Open Access
Predicting Outcomes Over Time in Patients With Heart Failure, Left Ventricular Systolic Dysfunction, or Both Following Acute Myocardial Infarction.
(J Am Heart Assoc, 2016-06-27) Lopes, Renato D; Pieper, Karen S; Stevens, Susanna R; Solomon, Scott D; McMurray, John JV; Pfeffer, Marc A; Leimberger, Jeffrey D; Velazquez, Eric J
BACKGROUND: Most studies of risk assessment or stratification in patients with myocardial infarction (MI) have been static and fail to account for the evolving nature of clinical events and care processes. We sought to identify predictors of mortality, cardiovascular death or nonfatal MI, and cardiovascular death or nonfatal heart failure (HF) over time in patients with HF, left ventricular systolic dysfunction, or both post-MI. METHODS AND RESULTS: Using data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial, we developed models to estimate the association between patient characteristics and the likelihood of experiencing an event from the time of a follow-up visit until the next visit. The intervals are: hospital arrival to discharge or 14 days, whichever occurs first; hospital discharge to 30 days; 30 days to 6 months; and 6 months to 3 years. Models were also developed to predict the entire 3-year follow-up period using baseline information. Multivariable Cox proportional hazards modeling was used throughout with Wald chi-squares as the comparator of strength for each predictor. For the baseline model of overall mortality, the 3 strongest predictors were age (adjusted hazard ratio [HR], 1.35; 95% CI, 1.28-1.42; P<0.0001), baseline heart rate (adjusted HR, 1.17; 95% CI, 1.14-1.21; P<0.0001), and creatinine clearance (≤100 mL/min; adjusted HR, 0.86; 95% CI, 0.84-0.89; P<0.0001). According to the integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices, the updated model had significant improvement over the model with baseline covariates only in all follow-up periods and with all outcomes. CONCLUSIONS: Patient information assessed closest to the time of the outcome was more valuable in predicting death when compared with information obtained at the time of the index hospitalization. Using updated patient information improves prognosis over using only the information available at the time of the index event.
Open Access
Prevalence and Outcomes of Left-Sided Valvular Heart Disease Associated With Chronic Kidney Disease.
(J Am Heart Assoc, 2017-10-11) Samad, Zainab; Sivak, Joseph A; Phelan, Matthew; Schulte, Phillip J; Patel, Uptal; Velazquez, Eric J
BACKGROUND: Chronic kidney disease (CKD) is an adverse prognostic marker for valve intervention patients; however, the prevalence and related outcomes of valvular heart disease in CKD patients is unknown. METHODS AND RESULTS: Included patients underwent echocardiography (1999-2013), had serum creatinine values within 6 months before index echocardiogram, and had no history of valve surgery. CKD was defined as diagnosis based on the International Classification of Diseases, Ninth Revision or an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Qualitative assessment determined left heart stenotic and regurgitant valve lesions. Cox models assessed CKD and aortic stenosis (AS) interaction for subsequent mortality; analyses were repeated for mitral regurgitation (MR). Among 78 059 patients, 23 727 (30%) had CKD; of these, 1326 were on hemodialysis. CKD patients were older; female; had a higher prevalence of hypertension, hyperlipidemia, diabetes, history of coronary artery bypass grafting/percutaneous coronary intervention, atrial fibrillation, and heart failure ≥mild AS; and ≥mild MR (all P<0.001). Five-year survival estimates of mild, moderate, and severe AS for CKD patients were 40%, 34%, and 42%, respectively, and 69%, 54%, and 67% for non-CKD patients. Five-year survival estimates of mild, moderate, and severe MR for CKD patients were 51%, 38%, and 37%, respectively, and 75%, 66%, and 65% for non-CKD patients. Significant interaction occurred among CKD, AS/MR severity, and mortality in adjusted analyses; the CKD hazard ratio increased from 1.8 (non-AS patients) to 2.0 (severe AS) and from 1.7 (non-MR patients) to 2.6 (severe MR). CONCLUSIONS: Prevalence of at least mild AS and MR is substantially higher and is associated with significantly lower survival among patients with versus without CKD. There is significant interaction among CKD, AS/MR severity, and mortality, with increasingly worse outcomes for CKD patients with increasing AS/MR severity.
Open Access
Race and Sex Differences in QRS Interval and Associated Outcome Among Patients with Left Ventricular Systolic Dysfunction.
(J Am Heart Assoc, 2017-03-20) Randolph, Tiffany C; Broderick, Samuel; Shaw, Linda K; Chiswell, Karen; Mentz, Robert J; Kutyifa, Valentina; Velazquez, Eric J; Gilliam, Francis R; Thomas, Kevin L
BACKGROUND: Prolonged QRS duration is associated with increased mortality among heart failure patients, but race or sex differences in QRS duration and associated effect on outcomes are unknown. METHODS AND RESULTS: We investigated QRS duration and morphology among 2463 black and white patients with heart failure and left ventricular ejection fraction ≤35% who underwent coronary angiography and 12-lead electrocardiography at Duke University Hospital from 1995 through 2011. We used multivariable Cox regression models to assess the relationship between QRS duration and all-cause mortality and investigate race-QRS and sex-QRS duration interaction. Median QRS duration was 105 ms (interquartile range [IQR], 92-132) with variation by race and sex (P<0.001). QRS duration was longest in white men (111 ms; IQR, 98-139) followed by white women (108 ms; IQR, 92-140), black men (100 ms; IQR, 91-120), and black women (94 ms; IQR, 86-118). Left bundle branch block was more common in women than men (24% vs 14%) and in white (21%) versus black individuals (12%). In black patients, there was a 16% increase in risk of mortality for every 10 ms increase in QRS duration up to 112 ms (hazard ratio, 1.16; 95% CI, 1.07, 1.25) that was not present among white patients (interaction, P=0.06). CONCLUSIONS: Black individuals with heart failure had a shorter QRS duration and more often had non-left bundle branch block morphology than white patients. Women had left bundle branch block more commonly than men. Among black patients, modest QRS prolongation was associated with increased mortality.
Open Access
Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose.
(J Cardiovasc Comput Tomogr, 2017-08-15) Lu, Michael T; Douglas, Pamela S; Udelson, James E; Adami, Elizabeth; Ghoshhajra, Brian B; Picard, Michael H; Roberts, Rhonda; Lee, Kerry L; Einstein, Andrew J; Mark, Daniel B; Velazquez, Eric J; Carter, William; Ridner, Michael; Al-Khalidi, Hussein R; Hoffmann, Udo
BACKGROUND: Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. METHODS: We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. RESULTS: Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ≥500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). CONCLUSION: Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550).
Open Access
Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).
(Circulation, 2018-02) Piña, Ileana L; Zheng, Qi; She, Lilin; Szwed, Hanna; Lang, Irene M; Farsky, Pedro S; Castelvecchio, Serenella; Biernat, Jolanta; Paraforos, Alexandros; Kosevic, Dragana; Favaloro, Liliana E; Nicolau, José C; Varadarajan, Padmini; Velazquez, Eric J; Pai, Ramdas G; Cyrille, Nicole; Lee, Kerry L; Desvigne-Nickens, Patrice; STICH Trial Investigators
Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study).The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex.At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment.Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.
Open Access
Six-minute walk distance after coronary artery bypass grafting compared with medical therapy in ischaemic cardiomyopathy.
(Open heart, 2018-01) Stewart, Ralph AH; Szalewska, Dominika; Stebbins, Amanda; Al-Khalidi, Hussein R; Cleland, John GH; Rynkiewicz, Andrzej; Drazner, Mark H; White, Harvey D; Mark, Daniel B; Roy, Ambuj; Kosevic, Dragana; Rajda, Miroslaw; Jasinski, Marek; Leng, Chua Yeow; Tungsubutra, Wiwun; Desvigne-Nickens, Patrice; Velazquez, Eric J; Petrie, Mark C
In patients with ischaemic left ventricular dysfunction, coronary artery bypass surgery (CABG) may decrease mortality, but it is not known whether CABG improves functional capacity.To determine whether CABG compared with medical therapy alone (MED) increases 6 min walk distance in patients with ischaemic left ventricular dysfunction and coronary artery disease amenable to revascularisation.The Surgical Treatment in Ischemic Heart disease trial randomised 1212 patients with ischaemic left ventricular dysfunction to CABG or MED. A 6 min walk distance test was performed both at baseline and at least one follow-up assessment at 4, 12, 24 and/or 36 months in 409 patients randomised to CABG and 466 to MED. Change in 6 min walk distance between baseline and follow-up were compared by treatment allocation.6 min walk distance at baseline for CABG was mean 340±117 m and for MED 339±118 m. Change in walk distance from baseline was similar for CABG and MED groups at 4 months (mean +38 vs +28 m), 12 months (+47 vs +36 m), 24 months (+31 vs +34 m) and 36 months (-7 vs +7 m), P>0.10 for all. Change in walk distance between CABG and MED groups over all assessments was also similar after adjusting for covariates and imputation for missing values (+8 m, 95% CI -7 to 23 m, P=0.29). Results were consistent for subgroups defined by angina, New York Heart Association class ≥3, left ventricular ejection fraction, baseline walk distance and geographic region.In patients with ischaemic left ventricular dysfunction CABG compared with MED alone is known to reduce mortality but is unlikely to result in a clinically significant improvement in functional capacity.NCT00023595.

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