Journal: Am Heart J

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Abstract

Primary percutaneous coronary intervention at centers with and without on-site surgical support: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).

Afana M, Gurm HS, Seth M, Frazier KM, Fielding S, Koenig GC
Primary percutaneous coronary intervention (PPCI) is being increasingly performed nationally at sites without on-site cardiac surgery; however, recent guidelines only provide a Class IIa recommendation for this practice. The state of Michigan has permitted PPCI without on-site surgery under a closely monitored system that mandates auditing of all procedures and quarterly feedback on quality and outcomes. This study sought to compare outcomes of patients undergoing PPCI at centers with and without on-site surgery in the state of Michigan.

Am Heart J: 30 Dec 2017; 195:99-107
Afana M, Gurm HS, Seth M, Frazier KM, Fielding S, Koenig GC
Am Heart J: 30 Dec 2017; 195:99-107 | PMID: 29224652
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Drug-induced cardiac abnormalities in premature infants and neonates.

Pesco-Koplowitz L, Gintant G, Ward R, Heon D, Saulnier M, Heilbraun J
The Cardiac Safety Research Consortium (CSRC) is a transparent, public-private partnership that was established in 2005 as a Critical Path Program and formalized in 2006 under a Memorandum of Understanding between the United States Food and Drug Administration and Duke University. Our continuing goal is to advance paradigms for more efficient regulatory science related to the cardiovascular safety of new therapeutics, both in the United States and globally, particularly where such safety questions add burden to innovative research and development. This White Paper provides a summary of discussions by a cardiovascular committee cosponsored by the CSRC and the US Food and Drug Administration (FDA) that initially met in December 2014, and periodically convened at FDA\'s White Oak headquarters from March 2015 to September 2016. The committee focused on the lack of information concerning the cardiac effects of medications in the premature infant and neonate population compared with that of the older pediatric and adult populations. Key objectives of this paper are as follows: Provide an overview of human developmental cardiac electrophysiology, as well as the electrophysiology of premature infants and neonates; summarize all published juvenile animal models relevant to drug-induced cardiac toxicity; provide a consolidated source for all reported drug-induced cardiac toxicities by therapeutic area as a resource for neonatologists; present drugs that have a known cardiac effect in an adult population, but no reported toxicity in the premature infant and neonate populations; and summarize what is not currently known about drug-induced cardiac toxicity in premature infants and neonates, and what could be done to address this lack of knowledge. This paper presents the views of the authors and should not be construed to represent the views or policies of the FDA or Health Canada.

Am Heart J: 30 Dec 2017; 195:14-38
Pesco-Koplowitz L, Gintant G, Ward R, Heon D, Saulnier M, Heilbraun J
Am Heart J: 30 Dec 2017; 195:14-38 | PMID: 29224642
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Abstract

A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.

Mauri L, Kario K, Basile J, Daemen J, ... Nanto S, Azizi M
Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure-lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE is designed to evaluate patients with resistant hypertension on standard of care medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood pressure will be assessed at 3months (primary end point). Both studies are enrolling patients, and their results are expected in 2018.

Am Heart J: 30 Dec 2017; 195:115-129
Mauri L, Kario K, Basile J, Daemen J, ... Nanto S, Azizi M
Am Heart J: 30 Dec 2017; 195:115-129 | PMID: 29224639
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Abstract

A randomized trial of continuous versus interrupted chest compressions in out-of-hospital cardiac arrest: Rationale for and design of the Resuscitation Outcomes Consortium Continuous Chest Compressions Trial.

Brown SP, Wang H, Aufderheide TP, Vaillancourt C, ... Nichol G, ROC Investigators
The Resuscitation Outcomes Consortium is conducting a randomized trial comparing survival with hospital discharge after continuous chest compressions without interruption for ventilation versus currently recommended American Heart Association cardiopulmonary resuscitation with interrupted chest compressions in adult patients with out-of-hospital cardiac arrest without obvious trauma or respiratory cause. Emergency medical services perform study cardiopulmonary resuscitation for 3 intervals of manual chest compressions (each ~2 minutes) or until restoration of spontaneous circulation. Patients randomized to the continuous chest compression intervention receive 200 chest compressions with positive pressure ventilations at a rate of 10/min without interruption in compressions. Those randomized to the interrupted chest compression study arm receive chest compressions interrupted for positive pressure ventilations at a compression:ventilation ratio of 30:2. In either group, each interval of compressions is followed by rhythm analysis and defibrillation as required. Insertion of an advanced airway is deferred for the first ≥6 minutes to reduce interruptions in either study arm. The study uses a cluster randomized design with every-6-month crossovers. The primary outcome is survival to hospital discharge. Secondary outcomes are neurologically intact survival and adverse events. A maximum of 23,600 patients (11,800 per group) enrolled during the post-run-in phase of the study will provide ≥90% power to detect a relative change of 16% in the rate of survival to discharge, 8.1% to 9.4% with overall significance level of 0.05. If this trial demonstrates improved survival with either strategy, >3,000 premature deaths from cardiac arrest would be averted annually.

Am Heart J: 01 Mar 2015; 169:334-341.e5
Brown SP, Wang H, Aufderheide TP, Vaillancourt C, ... Nichol G, ROC Investigators
Am Heart J: 01 Mar 2015; 169:334-341.e5 | PMID: 25728722
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Abstract

The relation between CYP2C19 genotype and phenotype in stented patients on maintenance dual antiplatelet therapy.

Gurbel PA, Shuldiner AR, Bliden KP, Ryan K, Pakyz RE, Tantry US
Both high platelet reactivity (HPR) and CYP2C19 genotyping have been proposed to stratify cardiovascular event risk and to personalize maintenance dual antiplatelet therapy (DAPT) in stented patients. However, how well CYP2C19 genotype correlates with HPR in patients on maintenance DAPT is less clear. We determined the association of CYP2C19 loss-of-function (⁎2) and gain-of-function (⁎17) allele status with platelet reactivity in 118 stented patients on DAPT ≥2 weeks and in 143 patients with stable coronary artery disease on aspirin therapy alone. Thirty-three percent and 39% carried at least 1 copy of ⁎2 and ⁎17 alleles, respectively. Neither allele was associated with platelet reactivity in patients on aspirin therapy alone. On DAPT, platelet aggregation was higher in those with ⁎2 allele than noncarriers (P ≤ .01) but did not differ between those with the ⁎17 allele and noncarriers. The prevalence of HPR using the 20 μM adenosine diphosphate-induced aggregation cutpoint was 34% in the total population: 26% in ⁎1/⁎1 homozygotes, 49% in those with the ⁎2 allele, and 20% in those with the ⁎17 allele (P = .006). Determination of diplotype status enhanced identification of HPR. However, platelet function on DAPT is highly variable within diplotype groups. Therefore, CYP2C19 genotype and HPR are imperfect correlates of each other. Because both predict cardiovascular events with similar risk ratios, CYP2C19 genotyping and HPR may provide complementary information to stratify risk and personalized DAPT in stented patients than either alone.

Am Heart J: 11 Mar 2011; 161:598-604
Gurbel PA, Shuldiner AR, Bliden KP, Ryan K, Pakyz RE, Tantry US
Am Heart J: 11 Mar 2011; 161:598-604 | PMID: 21392617
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Abstract

Health status and behavior among middle-school children in a midwest community: What are the underpinnings of childhood obesity?

Eagle TF, Gurm R, Goldberg CS, Durussel-Weston J, ... Jackson EA, Eagle KA
Background: Childhood obesity is one of the nation\'s foremost health challenges. How much of this is due to lifestyle choices? The objective of the study was to determine health behaviors that contribute to obesity in sixth-grade children. Methods: To assess which health habits contribute to childhood obesity, we studied body mass index, blood pressure, lipid profile, glucose, and heart rate recovery after a 3-minute step test among sixth-grade children enrolled in a school-based intervention study from 2004 to 2009, comparing health behaviors and physiologic markers in obese versus nonobese children. Univariate associations with obesity (P values ≤.10) were entered into a stepwise logistic regression to identify independent predictors. Results: Among 1,003 sixth graders (55% white, 15% African American; average age 11.5 years), 150 (15%) were obese. Obese students had higher levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, and recovery heart rates. They consumed more regular soda and school lunches but were less likely to engage in physical activities. Obese students were more likely to watch TV ≥2 hours per day. Independent predictors were watching TV or video games (odds ratio [OR] 1.19, 95% CI 1.06-1.33) and school lunch consumption (OR 1.29, 95% CI 1.02-1.64); moderate exercise was protective (OR 0.89, 95% CI 0.82-0.98). Conclusions: Obesity is present in 15% of our sixth graders and is associated with major differences in cardiovascular risk factors. Opportunities to improve childhood health should emphasize programs that increase physical activity, reduce recreational screen time, and improve nutritional value of school lunches. Whether genetic or not, childhood obesity can be attacked.

Am Heart J: 14 Dec 2010; 160:1185-1189
Eagle TF, Gurm R, Goldberg CS, Durussel-Weston J, ... Jackson EA, Eagle KA
Am Heart J: 14 Dec 2010; 160:1185-1189 | PMID: 21146676
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Abstract

Physiological mechanisms of pulmonary hypertension.

MacIver DH, Adeniran I, MacIver IR, Revell A, Zhang H
Pulmonary hypertension is usually related to obstruction of pulmonary blood flow at the level of the pulmonary arteries (eg, pulmonary embolus), pulmonary arterioles (idiopathic pulmonary hypertension), pulmonary veins (pulmonary venoocclusive disease) or mitral valve (mitral stenosis and regurgitation). Pulmonary hypertension is also observed in heart failure due to left ventricle myocardial diseases regardless of the ejection fraction. Pulmonary hypertension is often regarded as a passive response to the obstruction to pulmonary flow. We review established fluid dynamics and physiology and discuss the mechanisms underlying pulmonary hypertension. The important role that the right ventricle plays in the development and maintenance of pulmonary hypertension is discussed. We use principles of thermodynamics and discuss a potential common mechanism for a number of disease states, including pulmonary edema, through adding pressure energy to the pulmonary circulation.

Am Heart J: 22 Sep 2016; 180:1-11
MacIver DH, Adeniran I, MacIver IR, Revell A, Zhang H
Am Heart J: 22 Sep 2016; 180:1-11 | PMID: 27659877
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Abstract

Cholesterol efflux capacity: An introduction for clinicians.

Anastasius M, Kockx M, Jessup W, Sullivan D, Rye KA, Kritharides L
Epidemiologic studies have shown an inverse correlation between high-density lipoprotein (HDL) cholesterol (HDL-C) levels and cardiovascular disease outcomes. However, the hypothesis of a causal relationship between HDL-C and cardiovascular disease has been challenged by genetic and clinical studies. Serum cholesterol efflux capacity (CEC) is an important measure of HDL function in humans. Recent large clinical studies have shown a correlation between in vitro CEC and cardiovascular disease prevalence and incidence, which appears to be independent of HDL-C concentration. The present review summarizes recent large clinical studies and introduces important methodological considerations. Further studies are required to standardize and establish the reproducibility of this measure of HDL function and clarify whether modulating CEC will emerge as a useful therapeutic target.

Am Heart J: 22 Sep 2016; 180:54-63
Anastasius M, Kockx M, Jessup W, Sullivan D, Rye KA, Kritharides L
Am Heart J: 22 Sep 2016; 180:54-63 | PMID: 27659883
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Abstract

Individualized approaches to thromboprophylaxis in atrial fibrillation.

Ziff OJ, Camm AJ
Atrial fibrillation (AF) is the most common arrhythmia worldwide. The prevalence of AF in persons older than 55 years is at least 33.5 million globally and is predicted to more than double in the next half-century. Anticoagulation, heart rate control, and heart rhythm control comprise the 3 main treatment strategies in AF. Anticoagulation is aimed at preventing debilitating stroke, systemic embolism, and associated mortality. Historically, anticoagulation in AF was achieved with a vitamin K antagonist such as warfarin, which is supported by evidence demonstrating reduced incident stroke and all-cause mortality. However, warfarin has unpredictable pharmacokinetics with many drug-drug interactions that require regular monitoring to ensure patients remain in the therapeutic anticoagulant range. Non-vitamin K antagonist oral anticoagulants including dabigatran, rivaroxaban, apixaban, and edoxaban provide a possible solution to these issues with their more predictable pharmacokinetics, rapid onset of action, and greater specificity. Results from large randomized, controlled trials indicate that these agents are at least noninferior to warfarin in prevention of stroke. These trials also demonstrate a consistently lower incidence of intracranial hemorrhage, almost always all life-threatening bleeds, and many forms of major bleeds with the possible exception of gastrointestinal and some other forms of mucosal bleeding, compared with warfarin. Patients with AF are a heterogeneous population with diverse risk of stroke and bleeding, and different subgroups respond differently to anticoagulation. Important clinical questions have arisen regarding optimal anticoagulation drug selection in distinct populations such as those with renal impairment, older age, coronary artery disease, and heart failure as well as those at particularly high risk for bleeding or thromboembolism. In this review, treatment strategies in AF management are discussed in the context of different individual subgroups of patients.

Am Heart J: 26 Feb 2016; 173:143-58
Ziff OJ, Camm AJ
Am Heart J: 26 Feb 2016; 173:143-58 | PMID: 26920607
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Abstract

Linking clinical registry data with administrative data using indirect identifiers: Implementation and validation in the congenital heart surgery population.

Pasquali SK, Jacobs JP, Shook GJ, O\'Brien SM, ... Shah SS, Li JS
Background: The use of clinical registries and administrative data sets in pediatric cardiovascular research has become increasingly common. However, this approach is limited by relatively few existing datasets, each of which contain limited data, and do not communicate with one another. We describe the implementation and validation of methodology using indirect patient identifiers to link The Society of Thoracic Surgeons Congenital Heart Surgery (STS-CHS) Database to The Pediatric Health Information Systems (PHIS) Database (a pediatric administrative database). Methods: Centers submitting data to STS-CHS and PHIS during 2004 to 2008 were included (n = 30). Both data sets were limited to patients 0 to 18 years old undergoing cardiac surgery. An exact match was defined as an exact match on each of the following: date of birth, date of admission, date of discharge, sex, and center. Likely matches were defined as an exact match for all variables except ±1 day for one of the date variables. Results: Of 45,830 STS-CHS records, 87.4% matched to PHIS using the exact match criteria and 90.3% using the exact or likely match criteria. Validation in a subset of patients revealed that 100% of exact and likely matches were true matches. Conclusions: This analysis demonstrates that indirect identifiers can be used to create high-quality link between a clinical registry and administrative data set in the congenital heart surgery population. This methodology, which can also be applied to other data sets, allows researchers to capitalize on the strengths of both types of data and expands the pool of data available to answer important clinical questions.

Am Heart J: 14 Dec 2010; 160:1099-1104
Pasquali SK, Jacobs JP, Shook GJ, O'Brien SM, ... Shah SS, Li JS
Am Heart J: 14 Dec 2010; 160:1099-1104 | PMID: 21146664
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Abstract

Ultrafiltration in heart failure.

Fiaccadori E, Regolisti G, Maggiore U, Parenti E, ... Caiazza A, Cabassi A
Fluid overload is a key pathophysiologic mechanism underlying both the acute decompensation episodes of heart failure and the progression of the syndrome. Moreover, it represents the most important factor responsible for the high readmission rates observed in these patients and is often associated with renal function worsening, which by itself increases mortality risk. In this clinical context, ultrafiltration (UF) has been proposed as an alternative to diuretics to obtain a quicker relief of pulmonary/systemic congestion. This review illustrates technical issues, mechanisms, efficacy, safety, costs, and indications of UF in heart failure. The available evidence does not support the widespread use of UF as a substitute for diuretic therapy. Owing to its operative characteristics, UF cannot be expected to directly influence serum electrolyte levels, azotemia, and acid-base balance, or to remove high-molecular-weight substances (eg, cytokines) in clinically relevant amounts. Ultrafiltration should be used neither as a quicker way to achieve a sort of mechanical diuresis nor as a remedy for an inadequately prescribed and administered diuretic therapy. Instead, it should be reserved to selected patients with advanced heart failure and true diuretic resistance, as part of a more complex strategy aiming at an adequate control of fluid retention.

Am Heart J: 11 Mar 2011; 161:439-49
Fiaccadori E, Regolisti G, Maggiore U, Parenti E, ... Caiazza A, Cabassi A
Am Heart J: 11 Mar 2011; 161:439-49 | PMID: 21392597
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Abstract

Coronary atherosclerosis in outlier subjects at the opposite extremes of traditional risk factors: Rationale and preliminary results of the Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation (CAPIRE) study.

Magnoni M, Andreini D, Gorini M, Moccetti T, ... Maseri A, CAPIRE Study Group
Although it is generally accepted that cardiac ischemic events develop when coronary atherosclerosis (coronary artery disease [CAD]) has reached a critical threshold, this is true only to a first approximation. Indeed, there are patients with severe CAD who do not develop ischemic events; conversely, at the other extreme, individuals with minimal CAD may do. Similar exceptions to this paradigm include patients with diffuse CAD with a low risk factor (RF) profile and others with multiple RFs who develop only mild or no CAD. Therefore, the CAPIRE project was designed to investigate whether the specific study of these extreme outlier populations could provide clues for identification of yet unknown risk or protective factors for CAD and ischemic events. In the CAPIRE study, 481 subjects without previous symptoms or history of ischemic heart disease and normal left ventricular systolic function undergoing coronary computed tomography angiography have been selected based on coronary computed tomography angiography findings and cardiovascular RF profile. Therefore, in the whole population, 2 extreme outlier populations have been identified: (1) subjects with no CAD despite multiple RFs, and (2) at the opposite extreme, subjects with diffuse CAD despite a low-risk profile. Each subject has been characterized by clinical, anatomical imaging variables of CAD and baseline circulating biomarkers. Blood samples were collected and stored in a biological bank for further advanced investigations. The project is designed as a prospective, observational, international multicenter study with an initial cross-sectional analysis of clinical, imaging, and biomolecular variables in the selected groups and a longitudinal 5-year follow-up.

Am Heart J: 26 Feb 2016; 173:18-26
Magnoni M, Andreini D, Gorini M, Moccetti T, ... Maseri A, CAPIRE Study Group
Am Heart J: 26 Feb 2016; 173:18-26 | PMID: 26920592
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Abstract

Growth differentiation factor 15-an early marker of abnormal function of the Fontan circuit in patients with univentricular hearts.

Raedle-Hurst TM, Koenigstein K, Gruenhage F, Raedle J, Herrmann E, Abdul-Khaliq H
Background: In patients after the Fontan procedure, assessment of ventricular function is difficult and amino-terminal pro-B-type natriuretic peptide levels failed to be directly related to echocardiographic measures of systolic ventricular function. The aim of the study was to evaluate growth differentiation factor 15 (GDF-15), a marker of various stress pathways in the heart and extracardiac tissues. Methods: Plasma GDF-15 levels were measured in 38 consecutive patients after the Fontan procedure and compared to clinical, echocardiographic, and laboratory data; liver tissue stiffness; and venous hepatic flow velocities. Results: Mean GDF-15 levels were 987.2 ± 440.5 pg/mL in patients with an ejection fraction (EF) <50% as compared to 520.2 ± 143.1 pg/mL in those with an EF ≥50% (P < .001). Growth differentiation factor 15 levels were significantly related to the EF of the single ventricle (r = -0.66, P < .001), New York Heart Association functional class (r = 0.43, P = .008), and γGT levels (r = 0.50, P = .002) but weakly to liver tissue stiffness. According to receiver operating characteristic curve analysis, an EF <50% was best predicted by GDF-15 levels (area under the curve [AUC] 0.90, P < .001), peak venous hepatic flow at deep inspiration (AUC 0.89, P = .002), and age at Fontan operation (AUC 0.86, P = .001). Growth differentiation factor 15 and age at Fontan operation proved to be independent predictors in the multivariate analysis. The optimal cutoff of GDF-15 for the prediction of an EF <50% was calculated to be 613 pg/mL with a sensitivity of 90.0% and specificity of 85.7%. Conclusions: Growth differentiation factor 15 might be helpful in detecting early abnormal function of the Fontan circuit in patients with univentricular hearts. In patients with GDF-15 levels exceeding 613 pg/mL, further cardiac evaluation should be considered because impaired systolic function of the single ventricle may be present.

Am Heart J: 14 Dec 2010; 160:1105-1112
Raedle-Hurst TM, Koenigstein K, Gruenhage F, Raedle J, Herrmann E, Abdul-Khaliq H
Am Heart J: 14 Dec 2010; 160:1105-1112 | PMID: 21146665
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Abstract

Phase II trials in heart failure: The role of cardiovascular imaging.

Shah SJ, Fonarow GC, Gheorghiade M, Lang RM
The development of new therapies for heart failure (HF), especially acute HF, has proven to be quite challenging; and therapies evaluated in HF have greatly outnumbered treatments that are eventually successful in obtaining regulatory approval. Thus, the development of therapies for HF remains a vexing problem for pharmaceutical and device companies, clinical trialists, and health care professionals. Nowhere is this more apparent than in the phase II HF clinical trial, in which the goal is to determine whether an investigational agent should move forward to a phase III trial. Recent advancements in noninvasive cardiovascular imaging have allowed a new era of comprehensive phenotyping of cardiac structure and function in phase II HF trials. Besides using imaging parameters to predict success of subsequent phase III outcome studies, it is essential to also use imaging in phase II HF trials in a way that increases understanding of drug or device mechanism. Determination of the patients who would benefit most from a particular drug or device could decrease heterogeneity of phase III trial participants and lead to more successful HF clinical trials. In this review, we outline advantages and disadvantages of imaging various aspects of cardiac structure and function that are potential targets for therapy in HF, compare and contrast imaging modalities, provide practical advice for the use of cardiovascular imaging in drug development, and conclude with some novel uses of cardiac imaging in phase II HF trials.

Am Heart J: 11 Jul 2011; 162:3-15.e3
Shah SJ, Fonarow GC, Gheorghiade M, Lang RM
Am Heart J: 11 Jul 2011; 162:3-15.e3 | PMID: 21742085
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Abstract

Acute hyperglycemia and contrast-induced nephropathy in primary percutaneous coronary intervention.

Marenzi G, De Metrio M, Rubino M, Lauri G, ... Veglia F, Bartorelli AL
Background: Acute hyperglycemia and contrast-induced nephropathy (CIN) are frequently observed in ST-elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), and both are associated with an increased mortality rate. We investigated the possible association between acute hyperglycemia and CIN in patients undergoing primary PCI. Methods: We prospectively enrolled 780 STEMI patients undergoing primary PCI. For each patient, plasma glucose levels were assessed at hospital admission. Acute hyperglycemia was defined as glucose levels >198 mg/dL (11 mmol/L). Contrast-induced nephropathy was defined as an increase in serum creatinine >25% from baseline in the first 72 hours. Results: Overall, 148 (19%) patients had acute hyperglycemia; and 113 (14.5%) patients developed CIN. Patients with acute hyperglycemia had a 2-fold higher incidence of CIN than those without acute hyperglycemia (27% vs 12%, P < .001). In-hospital mortality was higher in patients with acute hyperglycemia than in those without acute hyperglycemia (12% vs 3%, P < .001). Mortality rate was also higher in patients developing CIN than in those without this renal complication (27% vs 0.9%, P < .001). Patients with acute hyperglycemia that developed CIN had the highest mortality rate (38%). Acute hyperglycemia was an independent predictor of CIN and in-hospital mortality. Conclusions: In STEMI patients undergoing primary PCI, acute hyperglycemia is associated with an increased risk for CIN and with increased in-hospital mortality.

Am Heart J: 14 Dec 2010; 160:1170-1177
Marenzi G, De Metrio M, Rubino M, Lauri G, ... Veglia F, Bartorelli AL
Am Heart J: 14 Dec 2010; 160:1170-1177 | PMID: 21146674
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A randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of intracoronary application of a novel bioabsorbable cardiac matrix for the prevention of ventricular remodeling after large ST-segment elevation myocardial infarction: Rationale and design of the PRESERVATION I trial.

Rao SV, Zeymer U, Douglas PS, Al-Khalidi H, ... Heyrman R, Krucoff MW
Postinfarction left ventricular (LV) remodeling can result in chronic heart failure and functional impairment. Although pharmacological strategies for established heart failure can be beneficial, preventing remodeling remains a challenge. Injectable bioabsorbable alginate or "bioabsorbable cardiac matrix" (BCM), composed of an aqueous mixture of sodium alginate and calcium gluconate, is a sterile colorless liquid that is a polysaccharide polymer produced from brown seaweed. When exposed to excess ionized calcium present in infarcted myocardium, BCM assembles to form a flexible gel, structurally resembling extracellular matrix, which provides temporary structural support to the infarct zone through and beyond the time needed for mature fibrotic tissue to develop. The PRESERVATION I trial is an early phase randomized, double-blind, placebo-controlled trial comparing intracoronary application of 4 mL of BCM with saline control in patients who develop large infarctions after successful reperfusion of large ST-segment elevation myocardial infarction (MI). Subjects will be randomized 2:1 to either BCM or saline control and will have the study device deployed through an intracoronary microcatheter in the infarct-related artery 2 to 5 days after index ST-segment elevation MI treated with successful primary or rescue percutaneous coronary intervention. The primary effectiveness end point is the absolute change in LV diastolic volume index as measured by 3-dimensional echocardiography from baseline to 6 months after BCM deployment. Secondary effectiveness end points include clinical outcomes, patient-reported quality of life, additional echocardiographic measures, and functional status measures. In summary, the PRESERVATION I trial is a randomized double-blind trial evaluating the effectiveness and safety of the novel device BCM in preventing LV remodeling patients who have large MIs despite undergoing successful primary or rescue percutaneous coronary intervention.

Am Heart J: 05 Nov 2015; 170:929-37
Rao SV, Zeymer U, Douglas PS, Al-Khalidi H, ... Heyrman R, Krucoff MW
Am Heart J: 05 Nov 2015; 170:929-37 | PMID: 26542501
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Planning the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a Collaborative Pan-Stakeholder Critical Path Registry Model: a Cardiac Safety Research Consortium "Incubator" Think Tank.

Al-Khatib SM, Calkins H, Eloff BC, Packer DL, ... Berliner E, Krucoff MW
Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience. These limitations of randomized trials of AF ablation, particularly with regard to safety issues, could be addressed using a synergistically structured national registry, which is the intention of the SAFARI. To facilitate discussions about objectives, challenges, and steps for such a registry, the Cardiac Safety Research Consortium and the Duke Clinical Research Institute, Durham, NC, in collaboration with the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, organized a Think Tank meeting of experts in the field. Other participants included the National Heart, Lung and Blood Institute, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the Society of Thoracic Surgeons, the AdvaMed AF working group, and additional industry representatives. The meeting took place on April 27 to 28, 2009, at the US Food and Drug Administration headquarters in Silver Spring, MD. This article summarizes the issues and directions presented and discussed at the meeting.

Am Heart J: 27 Jan 2010; 159:17-24
Al-Khatib SM, Calkins H, Eloff BC, Packer DL, ... Berliner E, Krucoff MW
Am Heart J: 27 Jan 2010; 159:17-24 | PMID: 20102862
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Drug-coated balloons to improve femoropopliteal artery patency: Rationale and design of the LEVANT 2 trial.

Jaff MR, Rosenfield K, Scheinert D, Rocha-Singh K, ... Nehler M, White CJ
Atherosclerotic peripheral artery disease (PAD) is common and results in limitations in quality of life and potential progression to limb loss. Options for therapy include medical therapy, supervised exercise, surgical revascularization, and, more recently, endovascular therapies to restore arterial perfusion to the limb. Endovascular revascularization has evolved over the past 2 decades, from percutaneous transluminal angioplasty (PTA) to self-expanding stents, atherectomy, laser angioplasty, and drug-eluting stents. Despite impressive technologic advances, PTA remains the standard of care at many institutions and is the recommended primary treatment modality for femoral-popliteal PAD according to current American College of Cardiology Foundation/American Heart Association guidelines. However, restenosis after PTA is common. Therefore, a significant clinical need remains for a device that is able to achieve more durable patency than PTA but does not require a permanent implant. Drug-coated balloons (DCBs) have the potential to address this need. Several randomized controlled clinical trials of PTA balloons coated with different formulations of paclitaxel have been conducted in Europe (N Engl J Med 2008;358:689-699) (Circulation 2008;118:1358-1365) (Circ Cardiovasc Interv 2012;5:831-840) (JACC Cardiovas Interv 2014;7:10-19) and demonstrated more durable efficacy than PTA with comparable safety. These studies were limited by small sample sizes and powered solely for an angiographic primary end point. The pivotal LEVANT 2 trial was designed in collaboration with the US Food and Drug Administration to demonstrate safety and efficacy in a large population and to obtain US Food and Drug Administration approval.

Am Heart J: 29 Mar 2015; 169:479-85
Jaff MR, Rosenfield K, Scheinert D, Rocha-Singh K, ... Nehler M, White CJ
Am Heart J: 29 Mar 2015; 169:479-85 | PMID: 25819854
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Impact:
Abstract

Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference.

Lai WW, Vetter VL, Richmond M, Li JS, ... Scott JD, Cohen MS
Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children\'s Hospital of Philadelphia and to the Morgan Stanley Children\'s Hospital of New York-Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD.

Am Heart J: 20 Dec 2010; 161:13-67
Lai WW, Vetter VL, Richmond M, Li JS, ... Scott JD, Cohen MS
Am Heart J: 20 Dec 2010; 161:13-67 | PMID: 21167335
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Abstract

Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy.

Trachtenberg B, Velazquez DL, Williams AR, McNiece I, ... Heldman AW, Hare JM
Although there is tremendous interest in stem cell (SC)-based therapies for cardiomyopathy caused by chronic myocardial infarction, many unanswered questions regarding the best approach remain. The TAC-HFT study is a phase I/II randomized, double-blind, placebo-controlled trial designed to address several of these questions, including the optimal cell type, delivery technique, and population. This trial compares autologous mesenchymal SCs (MSCs) and whole bone marrow mononuclear cells (BMCs). In addition, the study will use a novel helical catheter to deliver cells transendocardially. Although most trials have used intracoronary delivery, the optimal method is unknown and data suggest that the transendocardial approach may have important advantages. Several trials support the benefit of SCs in patients with chronic ischemic cardiomyopathy (ICMP), although the sample sizes have been small and the number of trials sparse. After a pilot phase of 8 patients, 60 patients with ICMP (left ventricular ejection fraction 15%-50%) will be randomized to group A (30 patients further randomized to receive MSC injection or placebo in a 2:1 fashion) or group B (30 patients further randomized to BMCs or placebo in a 2:1 fashion). All patients will undergo bone marrow aspiration and transendocardial injection of SCs or placebo. The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy (determined primarily by cardiac magnetic resonance imaging) of BMCs and MSCs administered transendocardially in patients with ICMP.

Am Heart J: 11 Mar 2011; 161:487-93
Trachtenberg B, Velazquez DL, Williams AR, McNiece I, ... Heldman AW, Hare JM
Am Heart J: 11 Mar 2011; 161:487-93 | PMID: 21392602
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Abstract

Impact of computerized dosing on eptifibatide-associated bleeding and mortality.

Putney DR, Kleiman NS, Fromm RE, Buergler JM
Objective: The study aimed to determine the impact on eptifibatide-associated bleeding by implementing a computerized dosing algorithm in the cardiac catheterization suite. Background: Excessive dosing of eptifibatide is associated with increased bleeding rates and hospital mortality. Although dosing adjustments based on renal function has been recommended, its implementation and clinical impact have not been assessed in daily practice. Methods: A computerized algorithm was implemented in January 2006 to calculate appropriate eptifibatide infusion dose (1 microg kg(-1) min(-1) for creatinine clearance <50 mL/min or 2 microg kg(-1) min(-1) for creatinine clearance >or=50 mL/min) using the Cockroft-Gault formula. All patients had hemoglobin measured before and the day after the procedure. Bleeding within 24 hours and mortality during hospitalization were compared in consecutive patients before and after implementation of the algorithm. Results: A total of 334 patients qualified for inclusion (pre-algorithm n = 91, post-algorithm n = 243). There was an increase in the proportion of patients receiving recommended doses of eptifibatide dosing (74.7% pre-algorithm vs 97.5% post-algorithm, P <or= .0001). Twenty-four-hour bleeding complications as classified using 3 major bleeding classification systems were reduced as was hospital mortality (4.4% vs 0%, P = .005). Packed red blood cell transfusion rates were similar between both groups (4.4% pre-algorithm vs 2.1% post-algorithm, P = .26). Conclusions: In patients receiving eptifibatide in the catheterization laboratory before percutaneous coronary intervention, implementation of a computerized algorithm was associated with appropriate dosing and reduced bleeding and mortality.

Am Heart J: 04 Dec 2009; 158:1018-23
Putney DR, Kleiman NS, Fromm RE, Buergler JM
Am Heart J: 04 Dec 2009; 158:1018-23 | PMID: 19958870
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Abstract

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trial.

The AIM-HIGH Investigators
ObjectiveS: The study aims to report the baseline characteristics of the fully randomized AIM-HIGH study population. Background: Residual risk persists despite aggressive low-density lipoprotein cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular (CV) disease, many of whom have atherogenic dyslipidemia (low levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and small dense LDL particles). Methods: All study participants had established CV disease and atherogenic dyslipidemia. Participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain LDL-C at 40 - 80 mg/dL (1.03-2.07 mmol/L) and were randomized to receive extended-release niacin or matching placebo. The primary end point is time to the first occurrence of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven coronary or cerebral revascularization with average follow-up of 4.1 years. Results: Between 2006 and 2010, 8,162 individuals signed consent to be screened, 4,275 began study drug run-in, and 3,414 were randomized to treatment. Mean age at entry was 64 ± 9 years, 85% were men, and 92% were white. As expected, risk factors were prevalent with 34% having diabetes; 71%, hypertension; and 81%, metabolic syndrome. Most participants had coronary artery disease (92%), whereas 11% had peripheral arterial disease; and 12%, cerebrovascular disease. Previous coronary revascularization occurred in 82%, and 54% reported a prior myocardial infarction. Among participants on a statin at entry (94%), mean baseline LDL-C was 71 mg/dL (1.84 mmol/L); mean HDL-C, 34.9 mg/dL (0.90 mmol/L); and median triglycerides, 161 mg/dL (1.82 mmol/L). SUMMARY: AIM-HIGH enrolled a high-risk group of patients with established atherosclerotic CV disease and atherogenic dyslipidemia. This study should determine whether there is incremental clinical benefit of niacin in reducing cardiovascular events in patients who have attained optimal on-treatment levels of LDL-C with a statin.

Am Heart J: 11 Mar 2011; 161:538-543
The AIM-HIGH Investigators
Am Heart J: 11 Mar 2011; 161:538-543 | PMID: 21392609
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Abstract

Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.

Ewe SH, Ajmone Marsan N, Pepi M, Delgado V, ... Biglioli P, Bax JJ
Background: This study aimed to evaluate the impact of baseline left ventricular (LV) systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation (TAVI). Survival of patients undergoing TAVI was also compared with that of a population undergoing surgical aortic valve replacement. Methods: One hundred forty-seven consecutive patients (mean age = 80 ± 7 years) undergoing TAVI in 2 centers were included. Mean follow-up period was 9.1 ± 5.1 months. Results: At baseline, 34% of patients had impaired LV ejection fraction (LVEF) (<50%) and 66% had normal LVEF (≥50%). Procedural success was similar in these 2 groups (94% vs 97%, P = .41). All patients achieved improvement in transvalvular hemodynamics. At follow-up, patients with a baseline LVEF <50% showed marked LV reverse remodeling, with improvement of LVEF (from 37% ± 8% to 51% ± 11%). Early and late mortality rates were not different between the 2 groups, despite a higher rate of combined major adverse cardiovascular events (MACEs) in patients with a baseline LVEF <50%. The predictors of cumulative MACEs were baseline LVEF (HR = 0.97, 95% CI = 0.94-0.99) and preoperative frailty (HR = 4.20, 95% CI = 2.00-8.84). In addition, long-term survival of patients with impaired or normal LVEF was comparable with that of a matched population who underwent surgical aortic valve replacement. Conclusions: TAVI resulted in significant improvement in LV function and survival benefit in high-risk patients with severe aortic stenosis, regardless of baseline LVEF. Patients with a baseline LVEF <50% were at higher risk of combined MACEs.

Am Heart J: 14 Dec 2010; 160:1113-1120
Ewe SH, Ajmone Marsan N, Pepi M, Delgado V, ... Biglioli P, Bax JJ
Am Heart J: 14 Dec 2010; 160:1113-1120 | PMID: 21146666
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Abstract

Reperfusion therapy for acute myocardial infarction: Concepts and controversies from inception to acceptance.

Rentrop KP, Feit F
More than 20 years of misconceptions derailed acceptance of reperfusion therapy for acute myocardial infarction (AMI). Cardiologists abandoned reperfusion for AMI using fibrinolytic therapy, explored in 1958, because they no longer attributed myocardial infarction to coronary thrombosis. Emergent aortocoronary bypass surgery, pioneered in 1968, remained controversial because of the misconception that hemorrhage into reperfused myocardium would result in infarct extension. Attempts to limit infarct size by pharmacotherapy without reperfusion dominated research in the 1970s. Myocardial necrosis was assumed to progress slowly, in a lateral direction. At least 18 hours was believed to be available for myocardial salvage. Afterload reduction and improvement of the microcirculation, but not reperfusion, were thought to provide the benefit of streptokinase therapy. Finally, coronary vasospasm was hypothesized to be the central mechanism in the pathogenesis of AMI. These misconceptions unraveled in the late 1970s. Myocardial necrosis was shown to progress in a transmural direction, as a "wave front," beginning with the subendocardium. Reperfusion within 6 hours salvaged a subepicardial ischemic zone in experimental animals. Acute angiography provided in vivo evidence of the high incidence of total coronary occlusion in the first hours of AMI. In 1978, early reperfusion by transluminal recanalization was shown to be feasible. The pathogenetic role of coronary thrombosis was definitively established in 1979 by demonstrating that intracoronary streptokinase rapidly restored flow in occluded infarct-related arteries, in contrast to intracoronary nitroglycerine which rarely did. The modern reperfusion era had dawned.

Am Heart J: 05 Nov 2015; 170:971-80
Rentrop KP, Feit F
Am Heart J: 05 Nov 2015; 170:971-80 | PMID: 26542507
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Abstract

Extent of ST-segment resolution after fibrinolysis adds improved risk stratification to clinical risk score for ST-segment elevation myocardial infarction.

Harkness JR, Sabatine MS, Braunwald E, Morrow DA, ... Cannon CP, Scirica BM
Background: The TIMI risk score (TRS) for ST-segment elevation myocardial infarction (STEMI) is a convenient validated clinical risk score for predicting mortality. Although not part of the risk score, ST-segment resolution (STRes) may provide a simple method of risk stratification based on the response to reperfusion. We sought to determine whether STRes provides incremental risk stratification to the TIMI risk score. Methods: The Clopidogrel as Adjunctive Reperfusion Therapy--Thrombolysis in Myocardial Infraction (CLARITY-TIMI 28) trial randomized STEMI patients receiving fibrinolysis to clopidogrel or placebo. A total of 2,340 patients had electrocardiograms (ECGs) valid to calculate STRes at 90 minutes, which was defined as complete (>70%), partial (30%-70%), or no resolution (30%). TRS was defined as low (0-2), medium (3-4), and high (> or =5). Clinical follow-up was through 30 days. Results were validated in 2,743 patients from the ExTRACT-TIMI 25 study. Results: The degree of STRes at 90 minutes after fibrinolysis correlated in a stepwise fashion with death or heart failure (5.1% complete STRes, 8.9% partial STRes, 13.4% no STRes, P < .001). Furthermore, the degree of STRes provided a consistent and significant gradient of risk across all risk score categories (low, medium, or high) and significantly improved the discriminatory ability of TIMI risk score to predict death or heart failure (c-statistic 0.69 for TIMI risk score alone and 0.74 with STRes added to the model, P < .001). With the inclusion of STRes to the TIMI risk score, 913 patients (39%) were reclassified to higher or lower risk groups, and the net reclassification improvement (NRI) was highly significant (P < .001). In the ExTRACT-TIMI 25 trial, addition of the STRes improved also the c-statistic (P = .012) and NRI (P < .001). Conclusions: The extent of STRes based on routinely obtained ECGs is an independent predictor of death and heart failure when used together with the TIMI risk score and significantly improves the ability to risk stratify patients after fibrinolysis.

Am Heart J: 27 Jan 2010; 159:55-62
Harkness JR, Sabatine MS, Braunwald E, Morrow DA, ... Cannon CP, Scirica BM
Am Heart J: 27 Jan 2010; 159:55-62 | PMID: 20102867
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Abstract

Increased mortality with left ventricular systolic dysfunction and heart failure in adults with myotonic dystrophy type 1.

Bhakta D, Groh MR, Shen C, Pascuzzi RM, Groh WJ
Background: Myotonic dystrophy type 1 (DM1) is a neurologic disorder with known cardiac involvement, including left ventricular systolic dysfunction (LVSD), heart failure (HF), atrioventricular and intraventricular conduction system disease, and sudden death. We studied the prevalence of these conditions and associated findings in a large population with DM1. Methods: History, physical examination, genetic testing, and electrocardiography were performed on 406 patients with DM1, and cardiac imaging was performed on 180 (44.3%) of these patients. Results: Left ventricular systolic dysfunction and clinical HF were found in 34 (18.9%) of 180 and in 23 (5.7%) of 406 of enrolled subjects, respectively, yielding an overall prevalence of LVSD/HF in 41 (10.1%) of 406. Increasing age, male sex, electrocardiographic conduction abnormalities, presence of atrial and ventricular arrhythmias, and implanted devices were all significantly associated with LVSD/HF, whereas cytosine-thiamine-guanine repeat length and neuromuscular severity score were not. The interval ≥240 milliseconds (relative risk 4.1, 95% CI 1.7-9.6, P = .001) and QRS duration ≥120 milliseconds (relative risk 4.2, 95% CI 2.0-8.5, P < .001) were significant predictors of LVSD/HF. The presence of LVSD/HF was also significantly associated with all-cause death (relative risk 3.9, 95% CI 2.3-6.4, P < .001) and cardiac death (relative risk 5.7, 95% CI 2.6-12.4, P < .001). Conclusions: A significant prevalence of LVSD/HF exists in patients with DM1. The presence of LVSD/HF in DM1 is significantly associated with all-cause and cardiac death.

Am Heart J: 14 Dec 2010; 160:1137-1141.e1
Bhakta D, Groh MR, Shen C, Pascuzzi RM, Groh WJ
Am Heart J: 14 Dec 2010; 160:1137-1141.e1 | PMID: 21146669
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Abstract

Race/ethnic disparities in left ventricular diastolic function in a triethnic community cohort.

Russo C, Jin Z, Homma S, Rundek T, ... Sacco RL, Di Tullio MR
Background: Racial-ethnic disparities exist in cardiovascular risk factors, morbidity, and mortality. Left ventricular diastolic dysfunction is a predictor of mortality and of cardiovascular outcome including incident heart failure. We sought to assess whether race-ethnic differences in diastolic function exist. Such differences may contribute to the observed disparities in cardiovascular outcomes. Methods: Two-dimensional echocardiography was performed in 760 participants (539 Hispanic, 117 non-Hispanic black, 104 non-Hispanic white) from the Cardiac Abnormalities and Brain Lesions study. Left ventricular diastolic function was assessed by standard Doppler flow profile and tissue Doppler imaging. Early (E) and late (A) transmitral diastolic flow, and mitral annulus early diastolic velocities (E\') were recorded; and E/A and E/E\' ratios were calculated. Results: Blacks and Hispanics had higher body mass index (P = .04, P < .01), higher prevalence of hypertension (both Ps </= .05) and diabetes (both Ps < .01), and lower level of education (both Ps < .01) compared with whites. In age- and sex-adjusted analyses, Hispanics and blacks showed worse indices of diastolic function than whites. Hispanics had lower E/A ratio (P = .01), lower E\', and higher E/E\' (both Ps < .01) than whites, whereas blacks had lower E\' (P < .05) and a trend toward a higher E/E\' ratio (P = .09) compared with whites. These race-ethnic differences in diastolic function were attenuated in multivariate models adjusted for cardiovascular risk factors. Conclusions: Differences in left ventricular diastolic function exist between race-ethnic groups. However, modifiable cardiovascular risk factors and sociodemographic variables, rather than intrinsic race-ethnic heterogeneity, seem to explain most of the observed differences.

Am Heart J: 05 Jul 2010; 160:152-158
Russo C, Jin Z, Homma S, Rundek T, ... Sacco RL, Di Tullio MR
Am Heart J: 05 Jul 2010; 160:152-158 | PMID: 20598986
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Abstract

Impaired physical quality of life in patients with diastolic dysfunction associates more strongly with neurohumoral activation than with echocardiographic parameters Quality of life in diastolic dysfunction.

Edelmann F, Stahrenberg R, Polzin F, Kockskämper A, ... Wachter R, Herrmann-Lingen C
Background: Quality of life (QoL) is impaired in diastolic heart failure. Little is known about QoL in diastolic dysfunction (DD) without heart failure. Methods: In the DIAST-CHF observational study, outpatients with risk factors for or a history of heart failure were included. In a cross-sectional analysis, we classified patients with preserved systolic function as having normal diastolic function (N, n = 264) or DD without (DD-, n = 957) or with (DD+, n = 321) elevated filling pressures according to echocardiography. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. Results: Short Form 36 physical function (SF-36-PF) was worse in DD+ (mean ± SD 67.2 ± 25.6) than in DD- (76.2 ± 22.7, P < .05) than in N (mean ± SD 81.1 ± 23.5, P < .01). Other physical dimensions and the physical component score were also lower in DD, whereas the mental component score did not differ. The SF-36-PF correlated weakly with echocardiographic indicators of diastolic function. In multivariate linear regression controlling for age, sex, body mass index, depressiveness as assessed by Patient Health Questionnaire 9, N-terminal probrain-type natriuretic peptide, and midregional proadrenomedullin (MR-proADM), individual echocardiographic parameters or grade of DD was not independently associated with SF-36-PF, whereas the presence of DD+ was. Both N-terminal probrain-type natriuretic peptide and MR-proADM were independently associated with SF-36-PF, with MR-proADM showing the stronger association. Conclusions: Physical dimensions of QoL are reduced in DD. Impaired SF-36-PF is only weakly associated with DD per se but rather seems to be contingent on the presence of elevated filling pressures. Biomarkers are more strongly and independently associated with SF-36-PF and may be more adequate surrogate markers of QoL in DD than echocardiographic measurements.

Am Heart J: 08 Apr 2011; 161:797-804
Edelmann F, Stahrenberg R, Polzin F, Kockskämper A, ... Wachter R, Herrmann-Lingen C
Am Heart J: 08 Apr 2011; 161:797-804 | PMID: 21473981
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Abstract

Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization.

Abdel-Qadir HM, Tu JV, Yun L, Austin PC, Newton GE, Lee DS
Background: The array of outcomes according to longitudinal furosemide doses in heart failure (HF) have not been evaluated. We examined the relationship of dynamic furosemide dose with mortality and hospitalizations for cardiovascular disease and renal dysfunction. Methods: Among elderly patients with HF (>/=65 years) newly discharged from hospital, dynamic furosemide exposure was determined by examining dose fluctuations up to 5 years of follow-up using the Ontario Drug Benefit pharmacare database. Dynamic furosemide exposures were classified as low dose (LD; 1-59 mg/d), medium dose (MD; 60-119 mg/d), or high dose (HD; >/=120 mg/d). Outcomes were assessed by modeling furosemide exposure as a time-dependent covariate. Results: Among 4,406 patients (78.4 +/- 7.0 years; 50.5% male), 46% changed furosemide dose categories within 1 year, and 63% changed dose categories over the follow-up period. High-dose furosemide patients were younger, were mostly male, and exhibited more ischemic or valvular disease, diabetes, atrial fibrillation, hypotension, hyponatremia, and higher baseline creatinine than LD. Compared with LD, MD exposure was associated with increased mortality with adjusted hazard ratio 1.96 (95% CI 1.79-2.15), whereas HD exposure conferred greater mortality risk with hazard ratio 3.00 (95% CI 2.72-3.31) after multiple covariate adjustment (both P < .001). Adjusted risks of hospitalization for HF (MD: 1.24 [95% CI 1.12-1.38] and HD: 1.43 [95% CI 1.26-1.63]), renal dysfunction (MD: 1.56 [95% CI 1.38-1.76] and HD: 2.16 [95% CI 1.88-2.49]), and arrhythmias (MD: 1.15 [95% CI 1.03-1.30] and HD: 1.45 [95% CI 1.27-1.66]) were also higher with increasing furosemide exposure. Conclusion: Exposure to higher furosemide doses is associated with worsened outcomes and is broadly predictive of death and morbidity.

Am Heart J: 09 Aug 2010; 160:264-271.e1
Abdel-Qadir HM, Tu JV, Yun L, Austin PC, Newton GE, Lee DS
Am Heart J: 09 Aug 2010; 160:264-271.e1 | PMID: 20691831
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Abstract

A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study.

Povsic TJ, Roe MT, Ohman EM, Steg PG, ... Bode C, Gibson CM
Dual antiplatelet therapy (DAPT), the combination of aspirin and a P2Y12 inhibitor, given for 12 months remains the standard of care after presentation with acute coronary syndrome (ACS) because it has been shown to be associated with a significant reduction in ischemic events compared with aspirin monotherapy. The factor Xa inhibitor rivaroxaban was shown to be associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, and stroke, and resulted in a nominal reduction in cardiovascular death, when added to background DAPT in the ATLAS ACS 2-TIMI 51 trial; however, there was excessive bleeding with this "triple-therapy" approach. The combination of rivaroxaban with P2Y12 inhibition in a "dual-pathway" approach may be an effective therapeutic regimen for the treatment of ACS, given the known importance of P2Y12 inhibition after stenting and intriguing data that the combination of an anticoagulant with clopidogrel after stenting in patients with atrial fibrillation appears an attractive option to this patient population. GEMINI-ACS-1 is a prospective, randomized, double-dummy, double-blind, active-controlled trial that will assess the safety of dual antithrombotic therapy (rivaroxaban [2.5 mg twice daily] + P2Y12 inhibitor) as compared with DAPT (aspirin [100 mg] + P2Y12 inhibitor) within 10 days of an ACS event in 3,000 patients. Patients will be randomized in a 1:1 ratio stratified by intended P2Y12 inhibitor use (clopidogrel 75 mg daily or ticagrelor 90 mg twice daily), with 1500 patients expected in each P2Y12 inhibitor strata. The primary end point is Thrombolysis in Myocardial Infarction clinically significant bleeding (major, minor, or requiring medical attention). The exploratory efficacy determination will be a composite of cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis. GEMINI-ACS-1 will assess the safety and feasibility of dual antithrombotic therapy with rivaroxaban and a P2Y12 inhibitor compared with conventional DAPT for the treatment for patients with recent ACS.

Am Heart J: 20 Mar 2016; 174:120-8
Povsic TJ, Roe MT, Ohman EM, Steg PG, ... Bode C, Gibson CM
Am Heart J: 20 Mar 2016; 174:120-8 | PMID: 26995378
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Abstract

Aerobic interval training versus continuous moderate exercise after coronary artery bypass surgery: a randomized study of cardiovascular effects and quality of life.

Moholdt TT, Amundsen BH, Rustad LA, Wahba A, ... Wisløff U, Slørdahl SA
Background: Peak oxygen uptake (Vo(2peak)) strongly predicts mortality in cardiac patients. We compared the effects of aerobic interval training (AIT) versus moderate continuous training (MCT) on Vo(2peak) and quality of life after coronary artery bypass grafting (CABG). Methods: Fifty-nine CABG patients were randomized to either AIT at 90% of maximum heart rate or MCT at 70% of maximum heart rate, 5 d/wk, for 4 weeks at a rehabilitation center. Primary outcome was Vo(2peak), at baseline, after rehabilitation (4 weeks), and after 6 months of home-based exercise (6 months). Results: Vo(2peak) increased between baseline and 4 weeks in AIT (27.1 +/- 4.5 vs 30.4 +/- 5.5 mL.kg(-1).min(-1), P < .001) and MCT (26.2 +/- 5.2 vs 28.5 +/- 5.6 mL.kg(-1).min(-1), P < .001; group difference, not significant). Aerobic interval training increased Vo(2peak) between 4 weeks and 6 months (30.4 +/- 5.5 vs 32.2 +/- 7.0 mL.kg(-1).min(-1), P < .001), with no significant change in MCT (28.5 +/- 5.6 vs 29.5 +/- 5.7 mL.kg(-1).min(-1)). Quality of life improved in both groups from baseline to 4 weeks, remaining improved at 6 months. There were no changes in echocardiographic systolic and diastolic left ventricular function. Adiponectin increased between 4 weeks and 6 months in both groups (group differences, not significant). Conclusions: Four weeks of intense training increased Vo(2peak) significantly after both AIT and MCT. Six months later, the AIT group had a significantly higher Vo(2peak) than MCT. The results indicate that AIT and MCT increase Vo(2peak) similarly in the short term, but with better long-term effect of AIT after CABG.

Am Heart J: 04 Dec 2009; 158:1031-7
Moholdt TT, Amundsen BH, Rustad LA, Wahba A, ... Wisløff U, Slørdahl SA
Am Heart J: 04 Dec 2009; 158:1031-7 | PMID: 19958872
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Abstract

Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure.

Hamaguchi S, Kinugawa S, Tsuchihashi-Makaya M, Goto K, ... Takeshita A, Tsutsui H
Background: The RALES trial demonstrated that spironolactone improved the prognosis of patients with heart failure (HF). However, it is unknown whether the discharge use of spironolactone is associated with better long-term outcomes among hospitalized systolic HF patients in routine clinical practice. We examined the effects of spironolactone use at discharge on mortality and rehospitalization by comparing with outcomes in patients who did not receive spironolactone. Methods: The JCARE-CARD studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed with an average of 2.2 years of follow-up. Results: A total of 946 patients had HF with reduced left ventricular ejection fraction (LVEF) (<40%), among whom spironolactone was prescribed at discharge in 435 patients (46%), but not in 511 patients (54%). The mean age was 66.3 years and 72.2% were male. Etiology was ischemic in 39.7% and mean LVEF was 27.1%. After adjustment for covariates, discharge use of spironolactone was associated with a significant reduction in all-cause death (adjusted hazard ratio 0.612, P = .020) and cardiac death (adjusted hazard ratio 0.524, P = .013). Conclusions: Among patients with HF hospitalized for systolic dysfunction, spironolactone use at the time of discharge was associated with long-term survival benefit. These findings provide further support for the idea that spironolactone may be useful in patients hospitalized with HF and reduced LVEF.

Am Heart J: 14 Dec 2010; 160:1156-1162
Hamaguchi S, Kinugawa S, Tsuchihashi-Makaya M, Goto K, ... Takeshita A, Tsutsui H
Am Heart J: 14 Dec 2010; 160:1156-1162 | PMID: 21146672
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Abstract

Primary percutaneous coronary intervention for acute myocardial infarction: Is it worth the wait? The risk-time relationship and the need to quantify the impact of delay.

Tarantini G, Van de Werf F, Bilato C, Gersh B
The efficacy of reperfusion therapy is dependent not only by the duration of symptoms before therapy but also by the baseline risk of the individual and the circumstances (time and context) of the occurrence. All these variables play a crucial role in determining the choice of best therapy (fibrinolysis or primary angioplasty [primary percutaneous coronary intervention, PPCI]), thereby confirming the admonition that one size does not fit all. It is generally accepted that patients are best served by PPCI when times to therapy are equal between PPCI and fibrinolysis, whereas pivotal issues that are less well supported by evidence include whether a single time interval is appropriate with regard to the "acceptable" PPCI-related delay and what degree of transfer-related delay is acceptable in patients presenting "early" to a non-percutaneous coronary intervention (PCI)-capable facility. The aim of this perspective is to use available data to individualize the approach to reperfusion therapy, taking into account temporal delays and the overall mortality risk on a case-by-case basis.

Am Heart J: 14 Feb 2011; 161:247-53
Tarantini G, Van de Werf F, Bilato C, Gersh B
Am Heart J: 14 Feb 2011; 161:247-53 | PMID: 21315205
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Abstract

Acute chest pain in the high-sensitivity cardiac troponin era: A changing role for noninvasive imaging?

Smulders MW, Kietselaer BL, Schalla S, Bucerius J, ... Wildberger JE, Bekkers SC
Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal.

Am Heart J: 13 Jun 2016; 177:102-11
Smulders MW, Kietselaer BL, Schalla S, Bucerius J, ... Wildberger JE, Bekkers SC
Am Heart J: 13 Jun 2016; 177:102-11 | PMID: 27297855
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Abstract

Current therapeutics and practical management strategies for pulmonary arterial hypertension.

Agarwal R, Gomberg-Maitland M
Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary vasculature and is characterized by a progressive rise in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. Currently, 3 classes of drugs are approved for the treatment of PAH based on results from small short-term clinical trials-prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. The pharmacologic management of PAH is rapidly evolving as newer therapeutic targets that stabilize or reverse pulmonary vascular disease and target right ventricular function are being sought and as clinical practice patterns shift in favor of earlier diagnosis and aggressive treatment. This manuscript will review the practical management aspects of currently approved PAH treatments and briefly discuss combination therapy and novel pharmacologic targets. In addition, the treatment of acute right ventricular failure and evidence (or lack thereof) for therapies in non-PAH pulmonary hypertension, such as pulmonary hypertension from left side of the heart disease, are addressed.

Am Heart J: 12 Aug 2011; 162:201-13
Agarwal R, Gomberg-Maitland M
Am Heart J: 12 Aug 2011; 162:201-13 | PMID: 21835279
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Abstract

Differential impact of race and risk factors on incidence of atrial fibrillation.

Gbadebo TD, Okafor H, Darbar D
Despite some common risk factors for atrial fibrillation (AF) being more prevalent among blacks, African Americans are increasingly being reported with lower prevalence and incidence of AF compared with whites. Contemporary studies have not provided a complete explanation for this apparent AF paradox in African Americans. Although many traditional and novel risk factors for AF have been identified, the role of ethnic-specific risk factors has not been examined. Whereas hypertension has been the most common risk factor associated with AF, coronary artery disease also plays an important role in AF pathophysiology in whites. Thereby, elucidating the role of ethnic-specific risk factors for AF may provide important insight into why African Americans are protected from AF or why whites are more prone to develop the arrhythmia. The link between AF susceptibility and genetic processes has only been recently uncovered. Polymorphisms in renin-angiotensin system genes have been characterized as predisposing to AF under certain environmental conditions. Several ion channel genes, signaling molecules, and several genetic loci have been linked with AF. Thereby, studies investigating genetic variants contributing to the differential AF risk in individuals of African American versus European ancestry may also provide important insight into the etiology of the AF paradox in blacks.

Am Heart J: 11 Jul 2011; 162:31-7
Gbadebo TD, Okafor H, Darbar D
Am Heart J: 11 Jul 2011; 162:31-7 | PMID: 21742087
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Abstract

The Cardiac Safety Research Consortium enters its second decade: An invitation to participate.

Turner JR, Kowey PR, Rodriguez I, Cabell CH, ... Krucoff MW, Cardiac Safety Research Consortium
The Cardiac Safety Research Consortium (CSRC), a transparent, public-private partnership established in 2005 as a Critical Path Program and formalized in 2006 under a Memorandum of Understanding between the United States Food and Drug Administration and Duke University, is entering its second decade. Our continuing goal is to advance paradigms for more efficient regulatory science related to the cardiovascular safety of new therapeutics, both in the United States and globally, particularly where such safety questions add burden to innovative research and development. Operationally, CSRC brings together a broad base of stakeholders from academia, industry, and government agencies in a collaborative forum focused on identifying barriers and then creating novel solutions through shared data, expertise, and collaborative research. This white paper provides a brief overview of the Consortium\'s activities in its first decade and a context for some of our current activities and future directions. The growth and success of the CSRC have been primarily driven by members\' active participation and the development of goodwill and trust throughout our membership, which have facilitated novel collaborations across traditionally competitive or contentious stakeholder boundaries. The continued expansion of our base of participating academicians, industry experts, and regulators will define the Consortium\'s success in our second decade. It is our hope that sharing our endeavors to date will stimulate additional participation in the CSRC and also provide a model for other groups starting to develop similar collaborative forums.

Am Heart J: 13 Jun 2016; 177:96-101
Turner JR, Kowey PR, Rodriguez I, Cabell CH, ... Krucoff MW, Cardiac Safety Research Consortium
Am Heart J: 13 Jun 2016; 177:96-101 | PMID: 27297854
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Abstract

Integrating the Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score into practice: Use, pitfalls, and new directions.

Capodanno D, Tamburino C
Risk stratification is key in optimizing care of patients undergoing percutaneous coronary intervention (PCI). Score algorithms, in particular, are useful prognostic tools to select the most appropriate strategy of treatment and help patients and their families to get a better understanding of issues relevant to treatment strategies and subsequent risks. Most scores tested in the setting of PCI focus on clinical variables. The SYNTAX score is a semiquantitative angiographic score developed to prospectively characterize the disease complexity of the coronary vasculature. This scoring system has recently been assessed in numerous cohorts of patients undergoing coronary revascularization by PCI or bypass surgery. When using the SYNTAX score, however, physicians are still challenged with a labor-intensive calculation and conflicting results from validation studies. Understanding how the SYNTAX score works, for which patients it works best, and whether it predicts accurately enough for its purpose is of paramount importance to get the maximum benefit from its application. The present article provides an overview of the background and the currently available evidences on the use of the SYNTAX score in patients undergoing coronary revascularization along with its limitations.

Am Heart J: 11 Mar 2011; 161:462-70
Capodanno D, Tamburino C
Am Heart J: 11 Mar 2011; 161:462-70 | PMID: 21392599
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Abstract

CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients.

Delgado-Lista J, Perez-Martinez P, Garcia-Rios A, Alcala-Diaz JF, ... Lopez-Miranda J, Perez-Jimenez F
Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secondary prevention. The objective of the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study, clinical trials number NCT00924937) is to compare the ability of a Mediterranean diet rich in virgin olive oil versus a low-fat diet to influence the composite incidence of cardiovascular events after 7 years in subjects with documented CHD at baseline. For this purpose, we enrolled 1,002 coronary patients from Spain. Baseline assessment (2009-2012) included detailed interviews and measurements to assess dietary, social, and biological variables. Results of baseline characteristics: The CORDIOPREV study in Spain describes a population with a high body mass index (37.2% overweight and 56.3% obesity) and with a median of low-density lipoprotein cholesterol of 88.5 mg/dL (70.6% of the patients having <100 mg/dL and 20.3% patients <70 mg/dL). A total of 9.6% of the participants were active smokers, and 64.4% were former smokers. Metabolic syndrome was present in 58% of this population. To sum up, we describe here the rationale, methods, and baseline characteristics of the CORDIOPREV study, which will test for the first time the efficacy of a Mediterranean diet rich in extra virgin olive oil as compared with a low-fat diet on the incidence of CHD recurrence in a long-term follow-up study.

Am Heart J: 13 Jun 2016; 177:42-50
Delgado-Lista J, Perez-Martinez P, Garcia-Rios A, Alcala-Diaz JF, ... Lopez-Miranda J, Perez-Jimenez F
Am Heart J: 13 Jun 2016; 177:42-50 | PMID: 27297848
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Abstract

Rationale and design of a randomized controlled trial of pneumococcal polysaccharide vaccine for prevention of cardiovascular events: The Australian Study for the Prevention through Immunization of Cardiovascular Events (AUSPICE).

Ren S, Hure A, Peel R, D\'Este C, ... Attia J, AUSPICE study group
Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event.

Am Heart J: 13 Jun 2016; 177:58-65
Ren S, Hure A, Peel R, D'Este C, ... Attia J, AUSPICE study group
Am Heart J: 13 Jun 2016; 177:58-65 | PMID: 27297850
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Abstract

ST-Segment resolution and clinical outcome with ischemic postconditioning and comparison to magnetic resonance.

Lønborg J, Holmvang L, Kelbæk H, Vejlstrup N, ... Jensen JS, Engstrøm T
Background: Ischemic postconditioning (IPost) during primary percutaneous coronary intervention (PPCI) is suggested to reduce myocardial damage. However, the association with ST-segment resolution (STR) and clinical outcome is not determined. The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome. Secondly, we sought to determine the relationship between STR and cardiac magnetic resonance (CMR) parameters in these patients. Methods: One hundred eighteen patients referred for PPCI were randomly assigned to either conventional PPCI or PPCI with IPost. In a single electrocardiographic lead, STR was determined. Treatment modalities were compared as regards STR, ST-segment elevation, and the number of patients achieving complete-STR (≥70%), incomplete-STR (30%-70%), and no-STR (<30%). Patients were evaluated for clinical outcome after 15 months. Furthermore, patients with and without complete-STR were compared as regards CMR parameters. Results: There was a tendency toward a better outcome with IPost for the number of patients achieving complete-STR (55% vs 63%; P = .09), ST-segment elevation (1.41 vs 1.12 mm; P = .07), and New York Heart Association class (P = .06). No difference in other cardiac events was observed. Furthermore, data determine that patients with complete-STR have smaller infarct size (12.9% vs 21.1%; P < .01) and a better ejection fraction (55.7% vs 47.7%; P < .01). Conclusions: Patients treated with IPost are suggested to have improved STR and New York Heart Association classification. Infarct size and the functional CMR parameters were better in the patients with complete-STR; as to this, single-lead STR remains an important predictor for successful treatment in patients treated with IPost.

Am Heart J: 14 Dec 2010; 160:1085-1091
Lønborg J, Holmvang L, Kelbæk H, Vejlstrup N, ... Jensen JS, Engstrøm T
Am Heart J: 14 Dec 2010; 160:1085-1091 | PMID: 21146662
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Abstract

Prognostic importance of a restrictive transmitral filling pattern in patients with symptomatic congestive heart failure and atrial fibrillation.

Raunsø J, Møller JE, Kjaergaard J, Akkan D, ... Køber L,
Background: Restrictive diastolic filling pattern is associated with increased mortality in patients with myocardial infarction and heart failure. Most studies have excluded patients with atrial fibrillation. The aim of the present study was to assess the prognostic value of a restrictive filling pattern in patients with atrial fibrillation. Methods: Doppler echocardiography including pulsed wave Doppler assessment of transmitral flow was performed in 880 patients with a clinical diagnosis of heart failure on hospital admission. Filling was considered restrictive when the mitral deceleration time <or=140 milliseconds. Results: On admission, 337 (39%) of the patients had atrial fibrillation. Among patients in atrial fibrillation, 170 (50%) had a restrictive filling; and in patients in sinus rhythm, 256 (47%) had restrictive filling (P = .34). During follow-up of median 6.7 years (range 5.3-7.8), 564 patients died (64%). Mortality was significantly higher in patients with a restrictive filling pattern irrespective of atrial fibrillation or sinus rhythm (P < .001). In a multivariable model only including patients in atrial fibrillation, a restrictive filling pattern remained a significant predictor of all-cause mortality (hazard ratio 1.79, 95% CI 1.24-2.58, P =.002). Conclusions: In a heterogeneous population hospitalized for symptomatic heart failure, a restrictive transmitral filling pattern during hospitalization is an ominous prognostic sign also in patients presenting with atrial fibrillation.

Am Heart J: 04 Dec 2009; 158:983-8
Raunsø J, Møller JE, Kjaergaard J, Akkan D, ... Køber L,
Am Heart J: 04 Dec 2009; 158:983-8 | PMID: 19958865
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Abstract

The Fat-Mass and Obesity-Associated (FTO) gene, physical activity, and risk of incident cardiovascular events in white women.

Ahmad T, Chasman DI, Mora S, Paré G, ... Ridker PM, Lee IM
Background: Variation in the Fat-Mass and Obesity-Associated (FTO) gene has been associated with obesity, diabetes, and hypertension. However, its association with cardiovascular disease (CVD) in healthy populations and any interaction with physical activity remain unclear. Methods: The FTO rs8050136 allele was determined in a prospective cohort study of 21,674 apparently healthy White US women in the Women\'s Genome Health Study. Results: During a mean follow-up of 12.7 ± 2.0 years, 664 incident CVD events occurred. The risk allele (A) was associated with higher prevalence of hypertension, diabetes, and metabolic syndrome (all P < .05). In a multivariate model, there was significant association of the risk allele with CVD (hazard ratio [HR] per allele copy 1.14, 95% CI 1.01-1.28) that was no longer significant after additional adjustment for body mass index (BMI) (HR 1.10, 95% CI 0.97-1.23). There was statistical evidence of an interaction between FTO and physical activity (P = .048). We found a significant association of FTO with CVD only among less-active (≤8.8 metabolic equivalent-h/wk) women (HR 1.19, 95% CI 1.02-1.38) in multivariate analyses that included BMI. More-active women did not have this increased risk (HR 0.96, 95% CI 0.79-1.16]). In a model that adjusted for BMI, less-active/high-risk (A/A) women were at 54% increased risk of developing CVD (HR 1.54, 95% CI 1.13-2.11), compared to more-active/low-risk (C/C) women. Conclusions: Carriers of the FTO risk allele have an increased risk of CVD mediated by BMI. There appears to be an interaction with physical activity, such that this risk increase is only in less-active women.

Am Heart J: 14 Dec 2010; 160:1163-1169
Ahmad T, Chasman DI, Mora S, Paré G, ... Ridker PM, Lee IM
Am Heart J: 14 Dec 2010; 160:1163-1169 | PMID: 21146673
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Abstract

The Brazilian Cardioprotective Nutritional Program to reduce events and risk factors in secondary prevention for cardiovascular disease: study protocol (The BALANCE Program Trial).

Weber B, Bersch-Ferreira ÂC, Torreglosa CR, Ross-Fernandes MB, ... Berwanger O, BALANCE Program Trial investigators
This article reports the rationale for the Brazilian Cardioprotective Nutritional Program (BALANCE Program) Trial. This pragmatic, multicenter, nationwide, randomized, concealed, controlled trial was designed to investigate the effects of the BALANCE Program in reducing cardiovascular events. The BALANCE Program consists of a prescribed diet guided by nutritional content recommendations from Brazilian national guidelines using a unique nutritional education strategy, which includes suggestions of affordable foods. In addition, the Program focuses on intensive follow-up through one-on-one visits, group sessions, and phone calls. In this trial, participants 45 years or older with any evidence of established cardiovascular disease will be randomized to the BALANCE or control groups. Those in the BALANCE group will receive the afore mentioned program interventions, while controls will be given generic advice on how to follow a low-fat, low-energy, low-sodium, and low-cholesterol diet, with a view to achieving Brazilian nutritional guideline recommendations. The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina. A total of 2468 patients will be enrolled in 34 sites and followed up for up to 48 months. If the BALANCE Program is found to decrease cardiovascular events and reduce risk factors, this may represent an advance in the care of patients with cardiovascular disease.

Am Heart J: 23 Dec 2015; 171:73-81.e2
Weber B, Bersch-Ferreira ÂC, Torreglosa CR, Ross-Fernandes MB, ... Berwanger O, BALANCE Program Trial investigators
Am Heart J: 23 Dec 2015; 171:73-81.e2 | PMID: 26699603
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Abstract

Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.

Holman RR, Bethel MA, George J, Sourij H, ... Zinman B, Hernandez AF
Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide-1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years. Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections. The trial will continue until 1,360 confirmed primary composite cardiovascular end points, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, have occurred. The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular end point. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once-weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide once-weekly is noninferior to usual care with respect to the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI is <1.30. EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT01144338.

Am Heart J: 20 Mar 2016; 174:103-10
Holman RR, Bethel MA, George J, Sourij H, ... Zinman B, Hernandez AF
Am Heart J: 20 Mar 2016; 174:103-10 | PMID: 26995376
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Abstract

Obesity and survival in patients with heart failure and preserved systolic function: A U-shaped relationship.

Kapoor JR, Heidenreich PA
Background: Studies document better survival in heart failure patients with decreased left ventricular ejection fraction (EF) and higher body mass index (BMI; kg/m(2)) compared to those with a lower BMI. However, it is unknown if this "obesity paradox" applies to heart failure patients with preserved EF or if it extends to the very obese (BMI >35). Methods: We determined all-cause mortality for 1,236 consecutive patients with a prior diagnosis of heart failure and a preserved EF (>/=50%). Results: Obesity (BMI>30) was noted in 542 patients (44%). The mean age was 71 +/- 12 years, but this varied depending on BMI. One-year all-cause mortality decreased with increasing BMI, except at BMI >45 where mortality began to increase (55% if BMI <20, 38% if BMI 20-25, 26% if BMI 26-30, 25% if BMI 31-35, 17% if BMI 36-40, 18% if BMI 41-45, and 25% if BMI>45, P < .001). After adjustment for patient age, history, medications, and laboratory and echocardiographic parameters, the hazard ratios for total mortality (relative to BMI 26-30) were 1.68 (95% CI, 1.04-2.69) for BMI <20, 1.25 (95% CI, 0.92-1.68) for BMI 20 to 25, 0.99 (95% CI, 0.71-1.36) for BMI 31-35, 0.58 (95% CI, 0.35-0.97) for BMI 36 to 40, 0.79 (95% CI, 0.44-1.4) for BMI 41 to 45, and 1.38 (95% CI 0.74-2.6) for BMI >45 (P < .0001). Conclusions: Low BMI is associated with increased mortality in patients with heart failure and preserved systolic function. However, with a BMI of >45, mortality increased, raising the possibility of a U-shaped relationship between BMI and survival.

Am Heart J: 27 Jan 2010; 159:75-80
Kapoor JR, Heidenreich PA
Am Heart J: 27 Jan 2010; 159:75-80 | PMID: 20102870
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Abstract

Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial.

Banovic M, Iung B, Bartunek J, Asanin M, ... Wojakowski W, Putnik S
Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors\' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients.

Am Heart J: 20 Mar 2016; 174:147-53
Banovic M, Iung B, Bartunek J, Asanin M, ... Wojakowski W, Putnik S
Am Heart J: 20 Mar 2016; 174:147-53 | PMID: 26995381
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Abstract

Predictable and SuStainable Implementation of National Cardiovascular Registries (PASSION) infrastructure: A think tank report from Medical Device Epidemiological Network Initiative (MDEpiNet).

Zeitler EP, Al-Khatib SM, Drozda JP, Kessler LG, ... Krucoff MW, MDEpiNet
The MDEpiNet is a public-private partnership between the US Food and Drug Administration\'s Center for Devices and Radiological Health and participating partners. The PASSION program is an MDEpiNet-sponsored program that aims to demonstrate the goals of MDEpiNet by using cardiovascular medical device registries to bridge evidence gaps across the medical device total product life cycle. To this end, a PASSION Think Tank meeting took place in October 2014 in Silver Spring, MD, to facilitate discussion between stakeholders about the successes, challenges, and future novel applications of medical device registries, with particular emphasis on identifying pilot projects. Participants spanned a broad range of groups including patients, device manufacturers, regulators, physicians/academicians, professional societies, providers, and payers. The meeting focus included 4 areas of cardiovascular medicine intended to cultivate interest in 4 MDEpiNet disease-specific/device-specific working groups: coronary intervention, electrophysiology, valvular disease, and peripheral vascular disease. In addition, more general issues applying to registry-based infrastructure and analytical methodologies for assessing device benefit/risk were considered to provide context for the working groups as PASSION programs going forward. This article summarizes the discussions at the meeting and the future directions of the PASSION program.

Am Heart J: 23 Dec 2015; 171:64-72.e2
Zeitler EP, Al-Khatib SM, Drozda JP, Kessler LG, ... Krucoff MW, MDEpiNet
Am Heart J: 23 Dec 2015; 171:64-72.e2 | PMID: 26699602
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Abstract

Altitude and the heart: is going high safe for your cardiac patient?

Higgins JP, Tuttle T, Higgins JA
Our aging population combined with the ease of travel and the interest in high altitude recreation pursuits exposes more patients to the acute physiologic effects of high altitude and lower oxygen availability. Acute exposure to high altitude is associated with significant alterations to the cardiovascular system. These may be important in patients with underlying cardiovascular disease who are not able to compensate to such physiologic changes. Exacerbating factors pertinent to patients with cardiovascular disease include acute hypoxia, increased myocardial work, increased epinephrine release, and increased pulmonary artery pressures. This review summarizes the physiology and clinical evidence regarding acute altitude exposure on the cardiopulmonary system with practical recommendations to address the question: "Is it safe for me to ski in the Rockies or climb Mt. Kilimanjaro?"

Am Heart J: 27 Jan 2010; 159:25-32
Higgins JP, Tuttle T, Higgins JA
Am Heart J: 27 Jan 2010; 159:25-32 | PMID: 20102863
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Abstract

Early clopidogrel use in non-ST elevation acute coronary syndrome and subsequent coronary artery bypass grafting.

Burke MA, Lee R, Fintel DJ
Clopidogrel use is associated with a significant decrease in major adverse cardiac events when used in patients with non-ST elevation acute coronary syndromes (NSTE-ACS), and guidelines give a class I level of evidence A recommendation for the use of clopidogrel in these patients. The optimal timing of clopidogrel use has not been conclusively determined, but nearly all data available support early use in patients with NSTE-ACS. Despite this, clopidogrel usage is far less than expected based on current guidelines because of concern for bleeding at the time of possible subsequent coronary artery bypass grafting (CABG). Clopidogrel use has been associated with increased perioperative bleeding at the time of CABG, but data are mixed. Numerous studies have conclusively shown that this bleeding risk is confined to those patients receiving clopidogrel within 5 days of CABG. The absolute number of patients exposed to this possible bleeding risk is very small relative to the >1 million patients who present annually with NSTE-ACS and is estimated to be <0.8% of these patients. Recent data have shown that (1) holding clopidogrel for 5 days before CABG is safe in patients with NSTE-ACS and (2) clopidogrel use in patients with NSTE-ACS decreases ischemic events in patients referred for CABG compared to patients who are not given clopidogrel. These data strongly challenge the notion that clopidogrel should be withheld until it is determined if the patient will be referred for CABG.

Am Heart J: 16 May 2011; 161:832-41
Burke MA, Lee R, Fintel DJ
Am Heart J: 16 May 2011; 161:832-41 | PMID: 21570511
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Abstract

Anthropometric measures after Fontan procedure: Implications for suboptimal functional outcome.

Cohen MS, Zak V, Atz AM, Printz BF, ... Dunbar-Masterson C, McCrindle BW
Background: Abnormal height and adiposity are observed after the Fontan operation. These abnormalities may be associated with worse functional outcome. Methods: We analyzed data from the National Heart, Lung, and Blood Institute Pediatric Heart Network cross-sectional study of Fontan patients. Groups were defined by height (z-score <-1.5 or ≥-1.5) and body mass index (body mass index [BMI] z-score <-1.5 or -1.5 to 1.5 or ≥1.5). Associations of anthropometric measures with measurements from clinical testing (exercise, echocardiography, magnetic resonance imaging) were determined adjusting for demographics, anatomy, and pre-Fontan status. Relationships between anthropometric measures and functional health status (FHS) were assessed using the Child Health Questionnaire. Results: Mean age of the cohort (n = 544) was 11.9 ± 3.4 years. Lower height-z patients (n = 124, 23%) were more likely to have pre-Fontan atrioventricular valve regurgitation (P = .029), as well as orthopedic and developmental problems (both P < .001). Lower height-z patients also had lower physical and psychosocial FHS summary scores (both P < .01). Higher BMI-z patients (n = 45, 8%) and lower BMI-z patients (n = 53, 10%) did not have worse FHS compared to midrange BMI-z patients (n = 446, 82%). However, higher BMI-z patients had higher ventricular mass-to-volume ratio (P = .03) and lower % predicted maximum work (P = .004) compared to midrange and lower BMI-z patients. Conclusions: Abnormal anthropometry is common in Fontan patients. Shorter stature is associated with poorer FHS and non-cardiac problems. Increased adiposity is associated with more ventricular hypertrophy and poorer exercise performance, which may have significant long-term implications in this at-risk population.

Am Heart J: 14 Dec 2010; 160:1092-1098.e1
Cohen MS, Zak V, Atz AM, Printz BF, ... Dunbar-Masterson C, McCrindle BW
Am Heart J: 14 Dec 2010; 160:1092-1098.e1 | PMID: 21146663
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Abstract

Randomized trial of aspirin and clopidogrel versus aspirin alone for the prevention of coronary artery bypass graft occlusion: the Preoperative Aspirin and Postoperative Antiplatelets in Coronary Artery Bypass Grafting study.

Sun JC, Teoh KH, Lamy A, Sheth T, ... Whitlock RP, Eikelboom JW
Background: Routine use of postoperative aspirin after coronary artery bypass grafting (CABG) reduces graft failure and cardiovascular events. The efficacy and safety of adding clopidogrel to aspirin for the prevention of graft failure and cardiovascular events after CABG are unknown. We performed a pilot study measuring safety and efficacy outcomes of aspirin and clopidogrel therapy after CABG. Methods: We randomized 100 patients undergoing CABG to receive placebo or clopidogrel started after surgery and for 30 days. All patients received aspirin 81 mg daily. Graft patency was measured by cardiac computed tomography angiography at 30 days. Results: Clinical follow-up was complete for 99 patients, and 79 (80%) underwent computed tomography angiography. The proportion of patients with ≥1 occluded graft was not significantly different between placebo and clopidogrel groups (9/39 [23.1%] vs 7/40 [17.5%], relative risk 0.95, 95% CI 0.80-1.14, P = .54). Among radial artery grafts, the placebo group had a significantly higher number of occlusions or "string signs" compared with the clopidogrel group (7/16 [43.8%] vs 2/19 [10.5%], relative risk 0.24, 95% CI 0.06-1.00, P = .05). There was no difference between placebo and clopidogrel groups in the safety outcomes of total postoperative bleeding, transfusions, bleeding events, and reexploration and in the efficacy outcomes of nonfatal myocardial infarction, stroke, and death. Conclusions: This pilot study confirms a high rate of graft occlusion after CABG surgery and suggests that the addition of clopidogrel to aspirin is feasible and safe and may be superior for prevention of graft failure in radial artery grafts.

Am Heart J: 14 Dec 2010; 160:1178-1184
Sun JC, Teoh KH, Lamy A, Sheth T, ... Whitlock RP, Eikelboom JW
Am Heart J: 14 Dec 2010; 160:1178-1184 | PMID: 21146675
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Abstract

Chronic noncommunicable cardiovascular and pulmonary disease in sub-Saharan Africa: An academic model for countering the epidemic.

Bloomfield GS, Kimaiyo S, Carter EJ, Binanay C, ... Tierney WM, Velazquez EJ
Noncommunicable diseases are rapidly overtaking infectious, perinatal, nutritional, and maternal diseases as the major causes of worldwide death and disability. It is estimated that, within the next 10 to 15 years, the increasing burden of chronic diseases and the aging of the population will expose the world to an unprecedented burden of chronic diseases. Preventing the potential ramifications of a worldwide epidemic of chronic noncommunicable diseases in a sustainable manner requires coordinated, collaborative efforts. Herein, we present our collaboration\'s strategic plan to understand, treat, and prevent chronic cardiovascular and pulmonary disease (CVPD) in western Kenya, which builds on a 2-decade partnership between academic universities in North America and Kenya, the Academic Model Providing Access to Healthcare. We emphasize the importance of training Kenyan clinician-investigators who will ultimately lead efforts in CVPD care, education, and research. This penultimate aim will be achieved by our 5 main goals. Our goals include creating an administrative core capable of managing operations, develop clinical and clinical research training curricula, enhancing existing technology infrastructure, and implementing relevant research programs. Leveraging a strong international academic partnership with respective expertise in cardiovascular medicine, pulmonary medicine, and medical informatics, we have undertaken to understand and counter CVPD in Kenya by addressing patient care, teaching, and clinical research.

Am Heart J: 16 May 2011; 161:842-7
Bloomfield GS, Kimaiyo S, Carter EJ, Binanay C, ... Tierney WM, Velazquez EJ
Am Heart J: 16 May 2011; 161:842-7 | PMID: 21570512
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Abstract

The ω-3 fatty acids for Prevention of Post-Operative Atrial Fibrillation trial-rationale and design.

Mozaffarian D, Marchioli R, Gardner T, Ferrazzi P, ... Tavazzi L, Tognoni G
Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25% to 60% of patients. Postoperative atrial fibrillation/flutter is associated with significant morbidity, higher long-term mortality, and increased health care costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain ω-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of ω-3-PUFAs supplementation on PoAF with mixed results. The OPERA trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether perioperative oral ω-3-PUFAs reduces occurrence of PoAF in patients undergoing cardiac surgery. Additional aims include evaluation of resource use, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a "real-world" population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total preoperative loading dose of 8 to 10 g of ω-3-PUFAs or placebo divided over 2 to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10, whichever comes first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to inform biologic pathways; proof of concept that ω-3-PUFAs influence cardiac arrhythmias; and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF.

Am Heart J: 11 Jul 2011; 162:56-63.e3
Mozaffarian D, Marchioli R, Gardner T, Ferrazzi P, ... Tavazzi L, Tognoni G
Am Heart J: 11 Jul 2011; 162:56-63.e3 | PMID: 21742090
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Abstract

Adjunctive anticoagulation during peripheral vascular intervention.

Donovan RJ, Ha J, Sumption KF, Dardik A, Jovin IS
Endovascular techniques for the treatment of peripheral arterial disease are becoming an increasingly common alternative to open surgery, yet the degree of anticoagulation and choice of anticoagulant to optimize outcomes in these procedures remain uncertain. To date, few randomized trials have directly compared different anticoagulants for use during peripheral vascular interventions. It is also unclear if the approach to anticoagulation should be individualized to each vascular bed or if common principles are shared among them. This has led practitioners across different specialties to use a variety of different methods for anticoagulation, with most extrapolated from techniques used in percutaneous coronary interventions. In this review, we analyze the current literature for anticoagulation used during peripheral vascular intervention of the lower extremity, renal, carotid, and aortic arteries, with special consideration to the choice of anticoagulant used to maximize safe and effective procedural outcomes.

Am Heart J: 08 Feb 2016; 172:106-14
Donovan RJ, Ha J, Sumption KF, Dardik A, Jovin IS
Am Heart J: 08 Feb 2016; 172:106-14 | PMID: 26856222
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Abstract

Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches.

Yaggi HK, Mittleman MA, Bravata DM, Concato J, ... Stoney CM, Redline S
Obstructive sleep apnea (OSA) significantly impacts cardiovascular health, demonstrated by observational investigations showing an independently increased risk of ischemic heart disease, diabetes, hypertension, congestive heart failure, acute coronary syndrome, stroke, cardiovascular mortality, and all-cause mortality. Positive airway pressure (PAP), a medical therapy for sleep apnea, reverses airway obstruction and may help reduce cardiovascular risk. Prior to planning large phase III randomized controlled trials to test the impact of PAP on cardiovascular outcomes, several gaps in knowledge need to be addressed. This article describes 2 independent studies that worked collaboratively to fill these gaps. The populations, design features, and relative benefits/challenges of the 2 studies (SleepTight and BestAIR) are described. Both studies were encouraged to have multidisciplinary teams with expertise in behavioral interventions to improve PAP compliance. Both studies provide key information that will be useful to the research community in future large-scale, event-driven, randomized trials to evaluate the efficacy and/or effectiveness of strategies to identify and treat significant OSA for decreasing risk of major adverse cardiovascular events in high-risk patients.

Am Heart J: 08 Feb 2016; 172:135-43
Yaggi HK, Mittleman MA, Bravata DM, Concato J, ... Stoney CM, Redline S
Am Heart J: 08 Feb 2016; 172:135-43 | PMID: 26856225
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Abstract

Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial). A multicenter, prospective, randomized, controlled clinical registry trial based on the Swedish angiography and angioplasty registry (SCAAR) platform. Study design and rationale.

Fröbert O, Lagerqvist B, Gudnason T, Thuesen L, ... Olivecrona GK, James SK
Background: In ST-elevation myocardial infarction (STEMI), distal embolization of thrombus material often precludes restoration of normal coronary artery flow. Small-scaled studies have demonstrated that intracoronary thrombus aspiration improves flow and myocardial perfusion, but only one larger randomized single-center study has suggested a survival benefit. Thrombus aspiration is widely used in clinical practice and is recommended by international guidelines despite limited evidence. METHODS/Design: The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia is a multicenter, prospective, randomized, controlled, clinical open-label trial based on the Swedish angiography and angioplasty registry (SCAAR) platform with blinded evaluation of end points. A total of 5,000 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) will randomly be assigned either to conventional PCI or to thrombus aspiration followed by PCI. SCAAR will be used as the platform for randomization, allowing a broad population of all-comers in the registry network to be enrolled. All follow-up will also be done in SCAAR and other national registries. The primary end point is time to all-cause death at 30 days. DISCUSSION: The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial is the largest trial to date to evaluate the effect of thrombus aspiration on death following PCI in patients with STEMI. We propose the term randomized clinical registry trial to describe the novel entity of using an online national registry as platform for case records, randomization, and follow-up.

Am Heart J: 14 Dec 2010; 160:1042-1048
Fröbert O, Lagerqvist B, Gudnason T, Thuesen L, ... Olivecrona GK, James SK
Am Heart J: 14 Dec 2010; 160:1042-1048 | PMID: 21146656
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Abstract

Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients.

Sellers MB, Newby LK
Atrial fibrillation (AF) affects 2.5 million patients in the United States. The incidence of this condition increases with age, such that approximately 5% of people >65 years of age have AF. Because of the lack of organized atrial contraction and thrombus formation in the left atrium, patients with AF are at increased risk of stroke. The estimated risk of stroke among all AF patients is 5% per year. Among patients without mitral stenosis, there is a graded relationship of stroke risk with the number of CHADS(2) risk factors. Warfarin is the recommended treatment for embolic stroke prophylaxis in AF in intermediate- to high-risk patients. However, elderly patients who are deemed to be at risk of falls are often not started on warfarin therapy secondary to a perceived higher risk of bleeding complications. These risks have been evaluated, but conclusive data regarding the risk-benefit trade-off are elusive. This review summarizes available data on the use of warfarin in elderly patients with AF, focusing on the risk of bleeding, and will specifically address the utility of falls risk assessment in the decision to initiate warfarin therapy for AF.

Am Heart J: 14 Feb 2011; 161:241-6
Sellers MB, Newby LK
Am Heart J: 14 Feb 2011; 161:241-6 | PMID: 21315204
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Abstract

Diagnosis and management issues in thoracic aortic aneurysm.

Booher AM, Eagle KA
Thoracic aortic enlargement is an increasingly recognized condition that is often diagnosed on imaging studies performed for unrelated indications. The risk of unrecognized and untreated aortic enlargement and aneurysm includes aortic rupture and dissection which carry a high burden of morbidity and mortality. The etiologies underlying thoracic aortic enlargement are diverse and can range from degenerative or hypertension associated aortic enlargement to more rare genetic disorders. Therefore, the evaluation and management of these patients can be complex and requires knowledge of the pathophysiology associated with thoracic aortic dilation and aneurysm. Additionally, there have been important advances in the treatment available to patients with thoracic aortic disease, including an increased role of endovascular therapy. Given the risk of mortality, increased clinical recognition and advances in therapeutics, the American College of Cardiology, American Heart Association and related professional societies have recently published guidelines on the management of thoracic aortic disease. This review focuses on the pathophysiology and various etiologies that lead to thoracic aortic aneurysm along with the diagnostic modalities and management of asymptomatic patients with thoracic aortic disease.

Am Heart J: 11 Jul 2011; 162:38-46.e1
Booher AM, Eagle KA
Am Heart J: 11 Jul 2011; 162:38-46.e1 | PMID: 21742088
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Abstract

High incidence of TIMI flow 0 to I in patients with ST-elevation myocardial infarction without electrocardiographic lytic criteria.

Figueras J, Ferreira-González I, Rizzo M, Alcalde O, ... Lidón RM, Cortadellas J
Background: Most patients with ST-elevation myocardial infarction fulfilling ST-segment elevation (STE) lytic criteria present an occluded culprit artery but the occlusion rate in those with minimal STE (minSTE) not fulfilling lytic criteria is unknown. Methods: In 63 patients with minSTE (mean STE:1.2 +/- 0.6 mm) and 149 with lytic STE criteria (lyticSTE, 4.8 +/- 3.1 mm), an emergency coronary angiography was performed, serial creatine kinase-MB was determined, and ejection fraction was measured by 2-dimensional echocardiography. Results: The 2 groups showed similar time from pain onset to electrocardiogram (minSTE 196 +/- 199 vs lyticSTE, 176 +/- 172 min, P = .444), and although time to catheterization was longer in patients with minSTE (426 +/- 314 vs 253 +/- 239 min, P < .001), the rate of TIMI flow 0 to I (88% vs 81%, P = .21) was similar and percutaneous coronary intervention was performed in >80% of patients from the 2 groups. Moreover, patients with minSTE had higher rate of collateral circulation (27% vs 13%, P = .013), lower rate of Q waves (44% vs 60%, P = .041), lower creatine kinase-MB (202 +/- 150 vs 335 +/- 280, microg/L, P < .001), higher ejection fraction (54% +/- 9% vs 49% +/- 12%, P = .004), and lower mortality (0% vs 7.4%, P = .036). Conclusions: ST-elevation myocardial infarction patients with minSTE present a high prevalence of TIMI flow 0 to I similar to those meeting lyticSTE suggesting an identical underlying mechanism and the potential to benefit from primary angioplasty.

Am Heart J: 04 Dec 2009; 158:1011-7
Figueras J, Ferreira-González I, Rizzo M, Alcalde O, ... Lidón RM, Cortadellas J
Am Heart J: 04 Dec 2009; 158:1011-7 | PMID: 19958869
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Abstract

Utility of positron emission tomography for drug development for heart failure.

Papadimitriou L, Smith-Jones PM, Sarwar CM, Marti CN, ... Parsey R, Butler J
Only about 1 in 5,000 investigational agents in a preclinical stage acquires Food and Drug Administration approval. Among many reasons for this includes an inefficient transition from preclinical to clinical phases, which exponentially increase the cost and the delays the process of drug development. Positron emission tomography (PET) is a nuclear imaging technique that has been used for the diagnosis, risk stratification, and guidance of therapy. However, lately with the advance of radiochemistry and of molecular imaging technology, it became evident that PET could help novel drug development process. By using a PET radioligand to report on receptor occupancy during novel agent therapy, it may help assess the effectiveness, efficacy, and safety of such a new medication in an early preclinical stage and help design successful clinical trials even at a later phase. In this article, we explore the potential implications of PET in the development of new heart failure therapies and review PET\'s application in the respective pathophysiologic pathways such as myocardial perfusion, metabolism, innervation, inflammation, apoptosis, and cardiac remodeling.

Am Heart J: 15 May 2016; 175:142-52
Papadimitriou L, Smith-Jones PM, Sarwar CM, Marti CN, ... Parsey R, Butler J
Am Heart J: 15 May 2016; 175:142-52 | PMID: 27179733
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Abstract

Prospective evaluation of the association between cardiac troponin T and markers of disturbed erythropoiesis in patients with heart failure.

Adams KF, Mehra MR, Oren RM, O\'Connor CM, ... Schwartz TA, Felker GM
Background: Elevated cardiac troponin T is a well-documented marker of cardiomyocyte damage and poor prognosis in patients with heart failure. We prospectively evaluated the relationship between this marker and hematopoietic disturbances in heart failure. Methods: Data were analyzed from 254 patients in the UNITE-HF Biomarker Registry, a prospective, observational, multicenter study of the clinical and biomarker correlates of anemia in heart failure. Logistic regression modeling assessed relationships between detectable troponin T and indices of hematologic function including anemia and red cell distribution width. Results: Anemia (hemoglobin ≤12 g/dL) was present in 65 of the 254 study patients, and detectable troponin T was found in 39. Anemia was a significant independent predictor of detectable troponin T in models that considered a number of clinical characteristics including renal function, functional class, heart rate, and systolic blood pressure (odds ratio 2.57, 95% CI 1.09-6.09, P = .032). Likewise, detectable troponin T was directly and independently related to red cell distribution width in similar multivariable analyses (odds ratio 1.36 per unit increase, 95% CI 1.08-1.71, P = .008). Conclusions: Anemia and increasing red cell distribution width were independently associated with elevated troponin T, a marker of cardiomyocyte injury or death in patients with heart failure.

Am Heart J: 14 Dec 2010; 160:1142-1148
Adams KF, Mehra MR, Oren RM, O'Connor CM, ... Schwartz TA, Felker GM
Am Heart J: 14 Dec 2010; 160:1142-1148 | PMID: 21146670
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Abstract

Switching of platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Review of the literature and practical considerations.

De Luca L, Capranzano P, Patti G, Parodi G
The combination of aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACSs) and in those undergoing percutaneous coronary intervention (PCI). At the present time, 3 different oral P2Y12 receptor inhibitors are available on the market; 2 have obtained the indication for ACS (clopidogrel and ticagrelor) and 1 for ACS with planned PCI (prasugrel). An intravenous direct acting P2Y12 inhibitor, cangrelor, has also been recently approved by US and European regulatory agencies for patients undergoing PCI. Although the correct timing and modality of transition from intravenous cangrelor to oral P2Y12 inhibitors is still controversial and needs further evidence, switching between oral P2Y12 receptor inhibitors frequently occurs in clinical practice for several reasons. This practice raises the question of the relative safety of this strategy and of which switching approaches are preferable. In this article, we review the data on switching antiplatelet treatment strategies with P2Y12 receptor inhibitors and discuss practical considerations for switching therapies in patients with ACS undergoing PCI.

Am Heart J: 05 Jun 2016; 176:44-52
De Luca L, Capranzano P, Patti G, Parodi G
Am Heart J: 05 Jun 2016; 176:44-52 | PMID: 27264219
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Abstract

The on- and off-target effects of morphine in acute coronary syndrome: A narrative review.

McCarthy CP, Mullins KV, Sidhu SS, Schulman SP, McEvoy JW
With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma.

Am Heart J: 05 Jun 2016; 176:114-121
McCarthy CP, Mullins KV, Sidhu SS, Schulman SP, McEvoy JW
Am Heart J: 05 Jun 2016; 176:114-121 | PMID: 27264228
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Abstract

Rationale and design of the Randomized Evaluation of patients with Stable angina Comparing Utilization of noninvasive Examinations (RESCUE) trial.

Stillman AE, Gatsonis C, Lima JA, Black WC, ... Udelson JE, Woodard PK
RESCUE is a phase III, randomized, controlled, multicenter, comparative efficacy study, designed to compare two diagnostic imaging/treatment paradigms that use coronary computed tomography angiography (CCTA) or single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) for assisting in the diagnosis of ischemic heart disease in patients with stable angina symptoms, and guiding subsequent treatment. The study is based on the hypothesis that CCTA as a diagnostic tool is associated with no increase in cardiac risk, decreased cost, and reduced radiation exposure compared with SPECT MPI. The RESCUE trial was funded by the Agency for Healthcare Research and Quality (AHRQ) and the American College of Radiology Imaging Network (ACRIN) Fund for Imaging Innovation, began in 2011, and completed in 2014.

Am Heart J: 05 Sep 2016; 179:19-28
Stillman AE, Gatsonis C, Lima JA, Black WC, ... Udelson JE, Woodard PK
Am Heart J: 05 Sep 2016; 179:19-28 | PMID: 27595676
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Abstract

Cardiovascular research in India: A perspective.

Vamadevan AS, Shah BR, Califf RM, Prabhakaran D
With cardiovascular disease (CVD) emerging as a major cause of mortality in India, clinical research in CVD is becoming increasingly important. There are several favorable factors that offer robust growth of clinical research infrastructure in India: well-established system of governance, a large investment in medical education infrastructure, growing interest in building capacity in clinical research, the presence of regulatory mechanisms governing clinical research, a large pharmaceutical industry, and a highly developed information technology and data processing infrastructure. However, the lack of trained research manpower, inadequate public spending on health, uneven distribution of health infrastructure, and the large prevalence of pretransitional diseases are major weakness in undertaking high-quality clinical research in CVD. Analysis of the contemporary scenario reveals that there are 3 important opportunities for clinical research in India: the need to identify low cost but cutting edge and context-specific interventions to address the health needs of India\'s large population, the potential for high-quality research, and the high degree of interest (domestically and internationally) in investing in clinical research education and infrastructure.

Am Heart J: 11 Mar 2011; 161:431-8
Vamadevan AS, Shah BR, Califf RM, Prabhakaran D
Am Heart J: 11 Mar 2011; 161:431-8 | PMID: 21392596
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Abstract

Admission and fasting plasma glucose for estimating risk of death of diabetic and nondiabetic patients with acute coronary syndrome: nonlinearity of hazard ratios and time-dependent comparison.

Cid-Alvarez B, Gude F, Cadarso-Suarez C, Gonzalez-Babarro E, ... Garcia-Acuna JM, Gonzalez-Juanatey JR
Background: In patients with acute coronary syndrome (ACS), increased plasma glucose levels are associated with worse outcome. Our aim is to ascertain the values of admission and fasting glucose for prediction of death among patients with ACS; and to compare their predictive capacities. Methods: The relationships of mortality to plasma glucose levels among 811 consecutive patients hospitalized with ACS were estimated using spline Cox models. Blood samples were obtained upon admission and after overnight fast. The predictive capacities of fasting and admission glucose were compared using time-dependent receiver operating characteristic curves. Results: Fasting and admission glucose levels were higher among the 151 patients who died (18.6%) than among survivors (P < .001). Among the 558 patients with no history of diabetes (68.8%) there was a J-shaped dependence of the all-time mortality hazard ratio on fasting glucose that persisted when adjusted for covariates: hazard was lowest at 110 mg/dL (6.1 mmol/L), and significantly greater at levels <90 mg/dL (5.0 mmol/L) or >117 mg/dL (6.5 mmol/L). Likewise among non-diabetic patients, the predictive capacities of admission and fasting glucose were similar for forecast times of up to about 1 year, but for later times the area under the receiver operating characteristic curve was larger for fasting glucose than admission glucose (P < .05). Neither admission nor fasting glucose levels discriminated among diabetic patients in regard to risk of death. Conclusions: Both admission and fasting glucose may be used for triage of nondiabetic ACS patients; fasting glucose may additionally be useful for long-term management, for which the relationship with the all-time mortality hazard ratio is J-shaped.

Am Heart J: 04 Dec 2009; 158:989-97
Cid-Alvarez B, Gude F, Cadarso-Suarez C, Gonzalez-Babarro E, ... Garcia-Acuna JM, Gonzalez-Juanatey JR
Am Heart J: 04 Dec 2009; 158:989-97 | PMID: 19958866
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Abstract

Defining nonvalvular atrial fibrillation: A quest for clarification.

Martins RP, Galand V, Colette E, Behar N, ... Daubert JC, Mabo P
Non-vitamin K oral anticoagulants (NOACs) are currently recommended for patients with nonvalvular atrial fibrillation since the publication of the 4 major pivotal trials evaluating the efficacy and safety of factor IIa and factor Xa inhibitors. The definition of nonvalvular atrial fibrillation is unclear, varying from one trial to another and even between North American and European guidelines, which is a source of uncertainties in clinical practice. However, many patients with atrial fibrillation present signs of valvular involvement, and clarification of this term is needed to not deny NOACs to patients based on the wrong perception that they may have valvular atrial fibrillation. The currently unique contraindications to NOACs are patients with mechanical heart valves and those with moderate-to-severe mitral stenosis, as stated by the recent 2015 position paper of the European Heart Rhythm Association. Patients with native heart valve involvement, regardless of their severity, are suitable for NOAC therapy. Patients with bioprosthetic heart valves and mitral valve repair may be suitable for NOACs except for the first 3 and the first 3-6 months postoperatively, respectively. Patients with transaortic valve implantation or percutaneous transluminal aortic valvuloplasty are also considered as being eligible for NOACs, although the bleeding risk has to be carefully considered in this population often requiring a combination with antiplatelet therapy. Future studies are warranted to increase the level of evidence of use of NOACs, particularly in patients with transaortic valve implantation and valvular surgery, and to determine whether they could be used in the future in the only 2 remaining contraindications.

Am Heart J: 08 Aug 2016; 178:161-7
Martins RP, Galand V, Colette E, Behar N, ... Daubert JC, Mabo P
Am Heart J: 08 Aug 2016; 178:161-7 | PMID: 27502864
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Abstract

Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: Results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry.

Melloni C, Shah BR, Ou FS, Roe MT, ... Peterson ED, Alexander KP
Background: Current American College of Cardiology/American Heart Association guidelines recommend initiation or intensification of statin therapy to achieve low-density lipoprotein cholesterol (LDL-C) goals after an acute coronary syndrome (ACS), yet little is known about the actual practice of intensifying lipid-lowering (LL) therapy and LDL-C achievement from hospital admission to 1-year follow-up. Methods: The MAINTAIN registry enrolled ACS patients from January 2006 through September 2007, collecting data on statin formulation, dose, and lipid profiles at both baseline and 12 months. Statin intensity (estimated LDL-C lowering) was categorized by formulation and dose as either moderate (<40%) or intensive (≥40%). In-hospital LL intensification is described and LDL goal attainment is reported for patients with complete baseline and 12-month lipid panels. Results: Of the 788 patients without contraindications to LL, 40% were on LL therapy before admission, and 89% at discharge. Among patients on LL therapy with LDL-C >100 mg/dL at admission, only 37% (n = 38) had their LL therapy intensified. Among 382 patients with 12 months of data, 89% (n = 341) were discharged on a statin. Of these, 89% were still on a statin at 12-month follow-up. A LDL-C goal of ≤100 mg/dL was achieved in 71% of patients, but the optional LDL-C goal ≤70 mg/dL was achieved in only 31%. Conclusions: Most high-risk ACS patients are prescribed statin therapy at hospital discharge and remain on therapy at 12-month follow-up. Despite this, the LDL-C goal of ≤70 mg/dL is achieved in a small minority. There is substantial opportunity to intensify LL therapy after ACS to achieve guideline LDL-C goals and prevent future morbidity and mortality.

Am Heart J: 14 Dec 2010; 160:1121-1129.e1
Melloni C, Shah BR, Ou FS, Roe MT, ... Peterson ED, Alexander KP
Am Heart J: 14 Dec 2010; 160:1121-1129.e1 | PMID: 21146667
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Abstract

A randomized, partially blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system in patients with acute coronary syndromes: Design and rationale of the RADAR Phase IIb trial.

Povsic TJ, Cohen MG, Mehran R, Buller CE, ... Becker RC, Alexander JH
Anticoagulants are the cornerstone of current acute coronary syndrome (ACS) therapy; however, anticoagulation regimens that aggressively reduce ischemic events are almost uniformly associated with more bleeding. REG1, an anticoagulation system, consists of RB006 (pegnivacogin), an RNA oligonucleotide factor IXa inhibitor, and RB007 (anivamersen), its complementary controlling agent. Phase I and IIa studies defined predictable relationships between doses of RB006, RB007, and degree of antifactor IX activity. The efficacy and safety of REG1 for the treatment of patients with ACS managed invasively and the safety of reversing RB006 with RB007 after cardiac catheterization are unknown. Randomized, partially-blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system compared to unfractionated heparin or low molecular heparin in subjects with acute coronary syndrome (RADAR) is designed to assess both the efficacy of the anticoagulant RB006 and the safety of a range of levels of RB006 reversal with RB007. The objectives of RADAR are (1) to determine the safety of a range of levels of RB006 reversal with RB007 after catheterization, (2) to confirm whether a dose of 1 mg/kg RB006 results in near-complete inhibition of factor IXa in patients with ACS, and (3) to assess the efficacy of RB006 as an anticoagulant in patients with ACS undergoing percutaneous coronary intervention.

Am Heart J: 14 Feb 2011; 161:261-268.e2
Povsic TJ, Cohen MG, Mehran R, Buller CE, ... Becker RC, Alexander JH
Am Heart J: 14 Feb 2011; 161:261-268.e2 | PMID: 21315207
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Abstract

Design and rationale of the HITTS randomized controlled trial: Effect of High-intensity Interval Training in de novo Heart Transplant Recipients in Scandinavia.

Nytrøen K, Yardley M, Rolid K, Bjørkelund E, ... Prescott EI, Gullestad L
There is no consensus on how, when, and at what intensity exercise should be performed and organized after heart transplantation (HTx). Most rehabilitation programs are conducted in HTx centers, which might be impractical and costly. We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in maintenance HTx recipients, but there are no studies among de novo patients, and whether HIT is feasible and superior to moderate training in HTx recipients is unclear. A total of 120 clinically stable HTx recipients older than 18 years will be recruited from 3 Scandinavian HTx centers. Participants are randomized to HIT or moderate training, shortly after surgery. All exercises are supervised in the patients\' local communities. Testing at baseline and follow-up includes the following: VO2peak (primary end point), muscle strength, body composition, quality of life, myocardial performance, endothelial function, biomarkers, and progression of cardiac allograft vasculopathy. A subgroup (n = 90) will also be tested at 3-year follow-up to assess long-term effects of exercise. So far, the HIT intervention is well tolerated, without any serious adverse events. We aim to test whether decentralized HIT is feasible, safe, and superior to moderate training, and whether it will lead to significant improvement in exercise capacity and less long-term complications.

Am Heart J: 08 Feb 2016; 172:96-105
Nytrøen K, Yardley M, Rolid K, Bjørkelund E, ... Prescott EI, Gullestad L
Am Heart J: 08 Feb 2016; 172:96-105 | PMID: 26856221
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Reducing the burden of disease and death from familial hypercholesterolemia: A call to action.

Knowles JW, O\'Brien EC, Greendale K, Wilemon K, ... Rader DJ, Khoury MJ
Familial hypercholesterolemia (FH) is a genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol, unrelated to diet or lifestyle. Untreated FH patients have 20 times the risk of developing coronary artery disease, compared with the general population. Estimates indicate that as many as 1 in 500 people of all ethnicities and 1 in 250 people of Northern European descent may have FH; nevertheless, the condition remains largely undiagnosed. In the United States alone, perhaps as little as 1% of FH patients have been diagnosed. Consequently, there are potentially millions of children and adults worldwide who are unaware that they have a life-threatening condition. In countries like the Netherlands, the United Kingdom, and Spain, cascade screening programs have led to dramatic improvements in FH case identification. Given that there are currently no systematic approaches in the United States to identify FH patients or affected relatives, the patient-centric nonprofit FH Foundation convened a national FH Summit in 2013, where participants issued a "call to action" to health care providers, professional organizations, public health programs, patient advocacy groups, and FH experts, in order to bring greater attention to this potentially deadly, but (with proper diagnosis) eminently treatable, condition.

Am Heart J: 02 Dec 2014; 168:807-11
Knowles JW, O'Brien EC, Greendale K, Wilemon K, ... Rader DJ, Khoury MJ
Am Heart J: 02 Dec 2014; 168:807-11 | PMID: 25458642
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Abstract

Aggressive hydraTion in patients with ST-Elevation Myocardial infarction undergoing Primary percutaneous coronary intervention to prevenT contrast-induced nephropathy (ATTEMPT): Study design and protocol for the randomized, controlled trial, the ATTEMPT, RESCIND 1 (First study for REduction of contraSt-induCed nephropathy followINg carDiac catheterization) trial.

Liu Y, Chen JY, Huo Y, Ge JB, ... Tan N, RESCIND group
Adequate hydration is recommended for acute ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) to prevent contrast-induced nephropathy (CIN). However, the optimal hydration regimen has not been well established in these high-risk patients. The objective of this study is to evaluate the efficacy of a preprocedural loading dose plus postprocedural aggressive hydration with normal saline guided by the left ventricular end-diastolic pressure (LVEDP) compared with general hydration for CIN prevention. The ATTEMPT study is a multicenter, open-label, investigator-driven, randomized controlled trial in China. Approximately 560 patients with STEMI undergoing primary PCI will be randomized (1:1) to receive either periprocedural general hydration (control group) or aggressive hydration (treatment group). Patients in the control group receive periprocedural general hydration with ≤500 mL normal saline (within 6 hours) at a normal rate (0.5 or 1 mL/kg · h). Patients in the treatment group receive a preprocedural loading dose (125/250 mL) of normal saline within 30 minutes and intravenous hydration at a normal rate until LVEDP is available, followed by postprocedural aggressive hydration guided by LVEDP for 4 hours and then continuous intravascular hydration at the normal rate until 24 hours after PCI. The primary end point is CIN, defined as a >25% or 0.5-mg/dL increase in serum creatinine from baseline during the first 48 to 72 hours after procedure. The ATTEMPT study has the potential to identify optimal hydration regimens for STEMI patients undergoing PCI.

Am Heart J: 08 Feb 2016; 172:88-95
Liu Y, Chen JY, Huo Y, Ge JB, ... Tan N, RESCIND group
Am Heart J: 08 Feb 2016; 172:88-95 | PMID: 26856220
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Abstract

The golden hour of prehospital reperfusion with triple antiplatelet therapy: A sub-analysis from the Ongoing Tirofiban in Myocardial Evaluation 2 (On-TIME 2) trial early initiation of triple antiplatelet therapy.

Heestermans T, van \'t Hof AW, Ten Berg JM, van Werkum JW, ... Zijlstra F, Hamm C
Background: It is known that the efficacy of thrombolytic therapy in ST-segment elevation myocardial infarction (STEMI) is highly time dependent with the best efficacy when given within the so-called golden hour. This analysis from the On-TIME 2 trial evaluated the efficacy of triple antiplatelet therapy on initial patency and ST-segment resolution (STR) in relation to time from symptom onset to first medical contact. Methods: The On-TIME 2 trial included 1,398 consecutive STEMI patients referred for primary percutaneous coronary intervention (PCI). Patients were randomized to dual (500 mg aspirin and 600 mg clopidogrel) or triple antiplatelet (500 mg aspirin, 600 mg clopidogrel, and tirofiban 25 μg/kg bolus and 0.15 μg/kg per minute maintenance infusion for 18 hours) pretreatment in the ambulance. Primary outcome of this sub-analysis was initial patency of the infarct-related vessel and STR before PCI according to time from symptom onset to first medical contact in quartiles. In addition, the incidence of aborted myocardial infarction, defined as the absence of a rise in creatinine kinase, was assessed. Results: Initial patency, STR before PCI, and the incidence of aborted myocardial infarction gradually increased with shorter time from symptom onset to first medical contact. Initial Thrombolysis in Myocardial Infarction flow was present in 21.2% in the total population and 26.2%, 21.5%, 18.1%, and 18.8% in the time quartiles, respectively (P for trend = .01). The incidence of complete STR pre-angiography was 16.6% in the total population and 23.4%, 18.2%, 14.7%, and 9.9% in the 4 quartiles, respectively (P for trend < .001). This was largely driven by the effect of triple antiplatelet therapy, which further improved initial patency and STR and led to a significantly higher incidence of aborted myocardial infarction (13.2% vs 8.7%, P = .011), especially in the patients with short duration of symptoms. Conclusion: Antiplatelet pretreatment before primary PCI, including a glycoprotein IIb/IIIa blocker, seems to be most effective when given shortly after symptom onset. Further studies should be performed to test this hypothesis.

Am Heart J: 14 Dec 2010; 160:1079-1084
Heestermans T, van 't Hof AW, Ten Berg JM, van Werkum JW, ... Zijlstra F, Hamm C
Am Heart J: 14 Dec 2010; 160:1079-1084 | PMID: 21146661
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Abstract

Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events) - DEVOTE 1.

Marso SP, McGuire DK, Zinman B, Poulter NR, ... Rabøl R, Buse JB
DEVOTE was designed to evaluate the cardiovascular safety of insulin degludec (IDeg) vs insulin glargine U100 (IGlar) in patients with T2D at high risk of cardiovascular events. DEVOTE is a phase 3b, multicenter, international, randomized, double-blind, active comparator-controlled trial, designed as an event-driven trial that would continue until 633 positively adjudicated primary events were accrued. The primary end point was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Patients with T2D at high risk of cardiovascular complications were randomized 1:1 to receive either IDeg or IGlar, each added to background therapies. This trial was designed to demonstrate statistical noninferiority of IDeg vs IGlar for the primary end point. DEVOTE enrolled 7,637 patients between October 2013 and November 2014 at 436 sites in 20 countries. Of these, 6,506 patients had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. DEVOTE was designed to provide conclusive evidence regarding the cardiovascular safety of IDeg relative to IGlar in a high-risk population of patients with T2D.

Am Heart J: 05 Sep 2016; 179:175-83
Marso SP, McGuire DK, Zinman B, Poulter NR, ... Rabøl R, Buse JB
Am Heart J: 05 Sep 2016; 179:175-83 | PMID: 27595693
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Abstract

Cardiovascular drugs that increase the risk of new-onset diabetes.

Ong KL, Barter PJ, Waters DD
The prevalence of type 2 diabetes is increasing worldwide, and diabetes is a strong adverse prognostic factor among patients with cardiovascular (CV) disease. Four classes of drugs that are commonly used for CV risk reduction, statins, niacin, thiazide diuretics, and ß-blockers, have been shown to increase the risk of new-onset diabetes (NOD) by 9% to 43% in meta-analyses or large-scale clinical trials. Clinical predictors for drug-related NOD appear to be similar to the predictors that have been described for NOD unrelated to drugs: fasting blood glucose >100 mg/dL and features of the metabolic syndrome such as body mass index >30 kg/m(2), serum triglycerides >150 mg/dL, and elevated blood pressure, among others. The mechanisms whereby these drugs increase the risk of NOD are incompletely understood, although different hypotheses have been suggested. Lifestyle intervention consisting of diet and exercise has been shown in multiple studies to reduce the risk of NOD by approximately 50%, with persistent benefit during long-term follow-up. In patients at high risk for NOD, niacin should be avoided, and for hypertension, an angiotensin-converting enzyme inhibitor or even a ß1-selective blocker might be a better choice than a standard ß-blocker. For thiazide diuretics and particularly statins, benefit in terms of CV event reduction outweighs the risk of NOD.

Am Heart J: 23 Mar 2014; 167:421-428
Ong KL, Barter PJ, Waters DD
Am Heart J: 23 Mar 2014; 167:421-428 | PMID: 24655688
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Abstract

Proceedings from duke resistant hypertension think tank.

Vemulapalli S, Ard J, Bakris GL, Bhatt DL, ... Califf RM, Patel MR
To identify patients at increased risk for cardiovascular outcomes, apparent treatment resistant hypertension (aTRH) is defined as having a blood pressure (BP) above goal despite the use of ≥3 antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. In light of growing scientific interest in the treatment of this group, a multistakeholder think tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field. Although recent epidemiologic studies in selected populations estimate that the prevalence of aTRH is 10% to 15% of hypertensive patients, further large-scale observational studies will be needed to better elucidate risk factors. To spur the development of therapies for aTRH, the development of an "aTRH" label for pharmacologic and device therapies with a developmental pathway including treatment added to the use of existing therapies is favored. Although demonstration of adequate BP lowering should be sufficient to gain Food and Drug Administration approval for therapies targeting aTRH, assessment of improvement in quality of life and cardiovascular outcomes is also desirable and considered in Centers for Medicare and Medicaid Services coverage decisions. Device trials under the aTRH label will need uniform and consistent processes for defining appropriate patient populations as well as postapproval registries assessing both long-term safety and duration of responses. Finally, patients with aTRH are likely to benefit from evaluation by a hypertension team to assure proper patient identification, diagnostic work-up, and therapeutic management before consideration of advanced or novel therapies to lower BP.

Am Heart J: 02 Jun 2014; 167:775-788.e1
Vemulapalli S, Ard J, Bakris GL, Bhatt DL, ... Califf RM, Patel MR
Am Heart J: 02 Jun 2014; 167:775-788.e1 | PMID: 24890525
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Abstract

Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure.

Tsutamoto T, Kawahara C, Nishiyama K, Yamaji M, ... Yamamoto T, Horie M
Background: Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are useful biomarkers in patients with chronic heart failure (CHF). However, the clinical use has limitations due to the low sensitivity of a conventional commercial assay system. Recently, a high sensitive-cTnI (hs-cTnI) commercial assay has become available. Methods: To compare the prognostic value of cTnT and hs-cTnI, we measured hemodynamic parameters and serum levels of cTnT, hs-cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP)in 258 consecutive CHF patients and then followed these patients for a mean period of 2.6 years. In both assays of cTnT and hs-cTnI, the lowest concentration at which the coeffi cient of variation was < or =10% were 0.03 ng/mL, respectively. Therefore, in the present study, an elevated cTnT or cTnI test was defined as a level of > or =0.03 ng/mL. Results: During long-term follow up, there were 20 cardiac deaths. In 258 CHF patients, serum cTnT were elevated (> or =0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI was elevated (> or =0.03 ng/mL) in 112 patients (43%). On stepwise multivariate analyses, high plasma NT-proBNP (> or =627 pg/mL, P = .0063) and hs-cTnI (> or =0.03 ng/mL) (P = .016) were independent significant prognostic predictors but cTnT (> or =0.03 ng/mL) was not. The hazard ratio for mortality of patients with high plasma NT-proBNP (> or =627 pg/mL) and hs-cTnI (> or =0.03 ng/mL) was 5.74 (95% CI, 2.33-14.28, P < .0001) compared to that of those with low NT-proBNP (<627 pg/mL) or hs-cTnI (<0.03 ng/mL). Conclusions: These findings indicate that a high plasma concentration of hs-cTnI is an independent and useful prognostic predictor in patients with CHF.

Am Heart J: 27 Jan 2010; 159:63-7
Tsutamoto T, Kawahara C, Nishiyama K, Yamaji M, ... Yamamoto T, Horie M
Am Heart J: 27 Jan 2010; 159:63-7 | PMID: 20102868
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Abstract

Rationale and design of the AngeLmed for Early Recognition and Treatment of STEMI trial: A randomized, prospective clinical investigation.

Gibson MC, Krucoff M, Fischell D, Fischell TA, ... Patel C, Holmes D
Significant improvements in door-to-balloon times have led to a reduction in mortality in ST-segment elevation myocardial infarction; however, mean symptom-to-door times remain at 2 to 3 hours. An intracardiac electrogram monitoring device may be beneficial in high-risk patients by alerting them to rapidly progressive ST-segment changes indicative of acute coronary occlusion. The Cardiosaver and DETECT phase I clinical studies demonstrated the safety, feasibility, and potential benefit of using an intracardiac electrogram monitoring device to alert the patient to seek medical attention. The goal of the randomized, prospective ALERTS Trial (Clinicaltrials.gov no. NCT00781118) is to evaluate the efficacy of an implantable monitoring device (IMD) in reducing the composite of either cardiac or unexplained death, new Q-wave myocardial infarction, or symptom-to-door time of >2 hours for confirmed thrombotic events. The IMD alerts the patient in real time when ST-segment deviation from a personalized baseline exceeds the trigger threshold. The trial is designed to enroll high-risk post-acute coronary syndrome patients or patients with previous multivessel coronary artery bypass surgery. All patients have the IMD implanted, with 1:1 unblinded randomization to the alerting feature being either turned on versus turned off for the first 6 months. Randomization occurs at the first follow-up visit, 7 to 14 days after the implantation of the IMD. Subjects then return for follow-up visits at months 1, 3, and 6 and thereafter every 6 months until closure of the investigational device exemption. Subjects who cannot be implanted successfully or who have the device explanted are removed from the study and followed up for a minimum of 30 days post-procedure. If a subject experiences a device-related complication and/or adverse experience, the subject is followed up until resolution or until the condition becomes stable and no further change is anticipated.

Am Heart J: 27 Jul 2014; 168:168-74
Gibson MC, Krucoff M, Fischell D, Fischell TA, ... Patel C, Holmes D
Am Heart J: 27 Jul 2014; 168:168-74 | PMID: 25066555
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Abstract

CYP2C19 genotype-guided antiplatelet therapy in ST-segment elevation myocardial infarction patients-Rationale and design of the Patient Outcome after primary PCI (POPular) Genetics study.

Bergmeijer TO, Janssen PW, Schipper JC, Qaderdan K, ... Deneer VH, Ten Berg JM
In patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI), the use of dual antiplatelet therapy is essential to prevent atherothrombotic complications. Therefore, patients are treated with acetylsalicylic acid and clopidogrel, prasugrel, or ticagrelor. Clopidogrel, however, shows a major interindividual variation in antiplatelet effect, which is correlated to an increase in atherothrombotic events in patients with high platelet reactivity. This interindividual variation is partly a result of CYP2C19 genetic variants. Ticagrelor and prasugrel reduce atherothrombotic events but increase bleeding rate and drug costs, as compared with clopidogrel. CYP2C19-based tailoring of antiplatelet therapy might be beneficial to STEMI patients.

Am Heart J: 22 Jun 2014; 168:16-22.e1
Bergmeijer TO, Janssen PW, Schipper JC, Qaderdan K, ... Deneer VH, Ten Berg JM
Am Heart J: 22 Jun 2014; 168:16-22.e1 | PMID: 24952855
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Abstract

Oral antiplatelet therapy for atherothrombotic disease: Current evidence and new directions.

White HD
Despite the proven efficacy of dual antiplatelet therapy with aspirin and one of the first-generation P2Y(12) antagonists (clopidogrel, prasugrel) in patients with atherothrombotic disease, residual ischemic risk remains substantial, and bleeding rates are increased. Incomplete protection against ischemic events can be attributed to the fact that these therapies each target a single platelet activation pathway, allowing continued platelet activation via other pathways, including the protease-activated receptor-1 (PAR-1) pathway stimulated by thrombin. Increased bleeding with dual antiplatelet therapy can be attributed to blockade of the thromboxane A(2) (by aspirin) and adenosine diphosphate (by P2Y(12) antagonist) platelet activation pathways that are essential to hemostasis. The second-generation P2Y(12) inhibitor ticagrelor plus aspirin demonstrated superior ischemic outcomes, including reduction in total mortality, versus clopidogrel plus aspirin, but event rates remain high, and major bleeding not related to coronary artery bypass grafting is increased. The novel P2Y(12) antagonist elinogrel, available in intravenous and oral formulations, may have a more favorable benefit-to-risk profile than existing agents in this class because of reversible and competitive binding to the P2Y(12) receptor. Inhibition of PAR-1 is an attractive, novel approach in antiplatelet therapy because it may provide incremental ischemic protection without increasing bleeding. The PAR-1 antagonist vorapaxar (SCH 530348) has been associated with favorable efficacy and safety in phase 2 trials. Two phase 3 trials are evaluating the efficacy and safety of vorapaxar in patients presenting with non-ST-segment elevation acute coronary syndromes and in patients with documented atherothrombotic disease.

Am Heart J: 11 Mar 2011; 161:450-61
White HD
Am Heart J: 11 Mar 2011; 161:450-61 | PMID: 21392598
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Abstract

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH).

The AIM-HIGH Investigators
Background: The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk. Methods: Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event. Results: AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012. SUMMARY: AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol.

Am Heart J: 11 Mar 2011; 161:471-477.e2
The AIM-HIGH Investigators
Am Heart J: 11 Mar 2011; 161:471-477.e2 | PMID: 21392600
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Abstract

Designing effective drug and device development programs for hospitalized heart failure: A proposal for pretrial registries.

Greene SJ, Shah AN, Butler J, Ambrosy AP, ... Vaduganathan M, Gheorghiade M
Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a "pretrial registry" as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site\'s ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012.

Am Heart J: 27 Jul 2014; 168:142-9
Greene SJ, Shah AN, Butler J, Ambrosy AP, ... Vaduganathan M, Gheorghiade M
Am Heart J: 27 Jul 2014; 168:142-9 | PMID: 25066552
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Abstract

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

Costanzo MR, Negoianu D, Fonarow GC, Jaski BE, ... Nabut JL, Schollmeyer MP
In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events.

Am Heart J: 18 Sep 2015; 170:471-82
Costanzo MR, Negoianu D, Fonarow GC, Jaski BE, ... Nabut JL, Schollmeyer MP
Am Heart J: 18 Sep 2015; 170:471-82 | PMID: 26385030
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Abstract

Rechanneling the cardiac proarrhythmia safety paradigm: A meeting report from the Cardiac Safety Research Consortium.

Sager PT, Gintant G, Turner JR, Pettit S, Stockbridge N
This white paper provides a summary of a scientific proposal presented at a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/Food and Drug Administration-sponsored Think Tank, held at Food and Drug Administration\'s White Oak facilities, Silver Spring, MD, on July 23, 2013, with the intention of moving toward consensus on defining a new paradigm in the field of cardiac safety in which proarrhythmic risk would be primarily assessed using nonclinical in vitro human models based on solid mechanistic considerations of torsades de pointes proarrhythmia. This new paradigm would shift the emphasis from the present approach that strongly relies on QTc prolongation (a surrogate marker of proarrhythmia) and could obviate the clinical Thorough QT study during later drug development. These discussions represent current thinking and suggestions for furthering our knowledge and understanding of the public health case for adopting a new, integrated nonclinical in vitro/in silico paradigm, the Comprehensive In Vitro Proarrhythmia Assay, for the assessment of a candidate drug\'s proarrhythmic liability, and for developing a public-private collaborative program to characterize the data content, quality, and approaches required to assess proarrhythmic risk in the absence of a Thorough QT study. This paper seeks to encourage multistakeholder input regarding this initiative and does not represent regulatory guidance.

Am Heart J: 27 Feb 2014; 167:292-300
Sager PT, Gintant G, Turner JR, Pettit S, Stockbridge N
Am Heart J: 27 Feb 2014; 167:292-300 | PMID: 24576511
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Abstract

The impact of drug shortages on patients with cardiovascular disease: causes, consequences, and a call to action.

Reed BN, Fox ER, Konig M, Jackevicius CA, ... Rabinstein AA, Page RL
Shortages of cardiovascular drugs have become increasingly common, representing an ongoing public health crisis. Given few therapeutic alternatives to many of the drugs in short supply, these shortages also pose a major challenge for cardiovascular care professionals. Although changes in the regulatory environment have led to some improvements in recent years, problems involving manufacturing processes remain the most common underlying cause. Because of the complex nature of drug shortages, sustainable solutions to prevent and mitigate them will require collaboration between regulatory agencies, drug manufacturers, and other key stakeholder groups. In this report, we describe the scope of the cardiovascular drug shortage crisis in the United States, including its underlying causes and the efforts currently being made to address it. Furthermore, we provide specific recommendations for how cardiovascular care professionals can be involved in efforts to limit the impact of drug shortages on patient care as well as policy changes aimed at preventing and mitigating them.

Am Heart J: 15 May 2016; 175:130-41
Reed BN, Fox ER, Konig M, Jackevicius CA, ... Rabinstein AA, Page RL
Am Heart J: 15 May 2016; 175:130-41 | PMID: 27179732
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Impact:
Abstract

Management patterns of non-ST segment elevation acute coronary syndromes in relation to prior coronary revascularization.

Elbarasi E, Goodman SG, Yan RT, Welsh RC, ... Canadian Acute Coronary Syndrome Registries I and II (ACS I and ACS II), Canadian Global Registry of Acute Coronary Events (GRACE/expanded-GRACE) Investigators
Background: Contemporary guidelines support an early invasive strategy for non-ST elevation acute coronary syndrome (NSTE-ACS) patients who had prior coronary revascularization. However, little is known about the management pattern of these patients in "real world." Methods: We analyzed 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events [GRACE]/expanded-GRACE) that recruited 12,483 NSTE-ACS patients from June 1999 to December 2007. We stratified the study population according to prior coronary revascularization status into 4 groups and compared their clinical characteristics, in-hospital use of medications, and cardiac procedures. Results: Of the 12,483 NSTE-ACS patients, 71.2% had no prior revascularization, 14.2% had percutaneous coronary intervention (PCI) only, 9.5% had coronary artery bypass graft surgery (CABG) only, and 5% had both PCI and CABG. Compared to their counterparts without prior revascularization, patients with previous PCI and/or CABG were more likely to be male, to have diabetes, myocardial infarction, and heart failure but less likely to have ST-segment deviation or positive cardiac biomarker on presentation. Early use of evidence-based medications was higher among patients with previous PCI only and lower among patients with previous CABG only. After adjusting for possible confounders including GRACE risk score, prior PCI was independently associated with in-hospital use of cardiac catheterization (adjusted odds ratio [OR] 1.18, 95% CI 1.04-1.34, P = .008). In contrast, previous CABG was an independent negative predictor (adjusted OR .77, 95% CI 0.68-0.87, P < .001). There was no significant interaction (P = .93) between previous PCI and CABG. Conclusions: The NSTE-ACS patients with previous PCI were more likely to be treated invasively. Conversely, patients with prior CABG less frequently received invasive therapy. Future studies should determine the appropriateness of this treatment discrepancy.

Am Heart J: 27 Jan 2010; 159:40-6
Elbarasi E, Goodman SG, Yan RT, Welsh RC, ... Canadian Acute Coronary Syndrome Registries I and II (ACS I and ACS II), Canadian Global Registry of Acute Coronary Events (GRACE/expanded-GRACE) Investigators
Am Heart J: 27 Jan 2010; 159:40-6 | PMID: 20102865
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Abstract

Automatic Optimization of Cardiac Resynchronization Therapy Using SonR-Rationale and Design of the Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the Paradym RF SonR CRT-D (RESPOND CRT) Trial.

Brugada J, Brachmann J, Delnoy PP, Padeletti L, ... Borri-Brunetto A, Singh JP
Although cardiac resynchronization therapy (CRT) is effective in most patients with heart failure (HF) and ventricular dyssynchrony, a significant minority of patients (approximately 30%) are non-responders. Optimal atrioventricular and interventricular delays often change over time and reprogramming these intervals might increase CRT effectiveness. The SonR algorithm automatically optimizes atrioventricular and interventricular intervals each week using an accelerometer to measure change in the SonR signal, which was shown previously to correlate with hemodynamic improvement (left ventricular [LV] dP/dtmax). The RESPOND CRT trial will evaluate the effectiveness and safety of the SonR optimization system in patients with HF New York Heart Association class III or ambulatory IV eligible for a CRT-D device. Enrolled patients will be randomized in a 2:1 ratio to either SonR CRT optimization or to a control arm employing echocardiographic optimization. All patients will be followed for at least 24 months in a double-blinded fashion. The primary effectiveness end point will be evaluated for non-inferiority, with a nested test of superiority, based on the proportion of responders (defined as alive, free from HF-related events, with improvements in New York Heart Association class or improvement in Kansas City Cardiomyopathy Questionnaire quality of life score) at 12 months. The required sample size is 876 patients. The two primary safety end points are acute and chronic SonR lead-related complication rates, respectively. Secondary end points include proportion of patients free from death or HF hospitalization, proportion of patients worsened, and lead electrical performance, assessed at 12 months. The RESPOND CRT trial will also examine associated reverse remodeling at 1 year.

Am Heart J: 23 Mar 2014; 167:429-36
Brugada J, Brachmann J, Delnoy PP, Padeletti L, ... Borri-Brunetto A, Singh JP
Am Heart J: 23 Mar 2014; 167:429-36 | PMID: 24655689
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Abstract

Atrial fibrillation: A major risk factor for cognitive decline.

Hui DS, Morley JE, Mikolajczak PC, Lee R
Atrial fibrillation is a common disease of the elderly, conferring considerable morbidity and mortality related to cardiovascular effects and thromboembolic risks. Anticoagulation, antiarrhythmic medications, and rate control are the cornerstone of contemporary management, whereas ablation and evolving surgical techniques continue to play important secondary roles. Growing evidence shows that atrial fibrillation is also a risk factor for significant cognitive decline through a multitude of pathways, further contributing to morbidity and mortality. At the same time, cognitive decline associated with cryptogenic strokes may be the first clue to previously undiagnosed atrial fibrillation. These overlapping associations support the concept of cognitive screening and rhythm monitoring in these populations. New research suggests modulating effects of currently accepted treatments for atrial fibrillation on cognition; however, there remains the need for large multicenter studies to examine the effects of novel oral anticoagulants, rhythm and rate control, and left atrial appendage occlusion on long-term cognitive function.

Am Heart J: 29 Mar 2015; 169:448-456
Hui DS, Morley JE, Mikolajczak PC, Lee R
Am Heart J: 29 Mar 2015; 169:448-456 | PMID: 25819850
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Abstract

The effect of renal denervation added to standard pharmacologic treatment versus standard pharmacologic treatment alone in patients with resistant hypertension: Rationale and design of the SYMPATHY trial.

Vink EE, de Beus E, de Jager RL, Voskuil M, ... Bots ML, Blankestijn PJ
The first studies on renal denervation (RDN) suggest that this treatment is feasible, effective, and safe in the short term. Presently available data are promising, but important uncertainties exist; therefore, SYMPATHY has been initiated. SYMPATHY is a multicenter, randomized, controlled trial in patients randomized to RDN in addition to usual care (intervention group) or to continued usual care (control group). Randomization will take place in a ratio of 2 to 1. At least 300 participants will be included to answer the primary objective. Sample size may be extended to a maximum of 570 to address key secondary objectives. The primary objective is to assess whether RDN added to usual care compared with usual care alone reduces blood pressure (BP) (ambulatory daytime systolic BP) in subjects with an average daytime systolic BP ≥135, despite use of ≥3 BP-lowering agents, 6 months after RDN. Key secondary objectives are evaluated at 6 months and at regular intervals during continued follow-up and include the effect of RDN on the use of BP-lowering agents, in different subgroups (across strata of estimated glomerular filtration rate and of baseline BP), on office BP, quality of life, and cost-effectiveness.

Am Heart J: 27 Feb 2014; 167:308-314.e3
Vink EE, de Beus E, de Jager RL, Voskuil M, ... Bots ML, Blankestijn PJ
Am Heart J: 27 Feb 2014; 167:308-314.e3 | PMID: 24576513
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Impact:

This program is still in alpha version.