Journal: Am J Cardiol

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Abstract

Using Metabolic Equivalents in Clinical Practice.

Franklin BA, Brinks J, Berra K, Lavie CJ, Gordon NF, Sperling LS
Metabolic equivalents, or METs, are routinely employed as a guide to exercise training and activity prescription and to categorize cardiorespiratory fitness (CRF). There are, however, inherent limitations to the concept, as well as common misapplications. CRF and the patient\'s capacity for physical activity are often overestimated and underestimated, respectively. Moreover, frequently cited fitness thresholds associated with the highest and lowest mortality rates may be misleading, as these are influenced by several factors, including age and gender. The conventional assumption that 1 MET = 3.5 mL O2/kg/min has been challenged in numerous studies that indicate a significant overestimation of actual resting energy expenditure in some populations, including coronary patients, the morbidly obese, and individuals taking β-blockers. These data have implications for classifying relative energy expenditure at submaximal and peak exercise. Heart rate may be used to approximate activity METs, resulting in a promising new fitness metric termed the \"personal activity intelligence\" or PAI score. Despite some limitations, the MET concept provides a useful method to quantitate CRF and define a repertoire of physical activities that are likely to be safe and therapeutic. In conclusion, for previously inactive adults, moderate-to-vigorous physical activity, which corresponds to ≥3 METs, may increase MET capacity and decrease the risk of future cardiac events.

Am J Cardiol: 31 Jan 2018; 121:382-387
Franklin BA, Brinks J, Berra K, Lavie CJ, Gordon NF, Sperling LS
Am J Cardiol: 31 Jan 2018; 121:382-387 | PMID: 29229271
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Abstract

Meta-Analysis of the Safety and Efficacy of the Oral Anticoagulant Agents (Apixaban, Rivaroxaban, Dabigatran) in Patients With Acute Coronary Syndrome.

Khan SU, Arshad A, Riaz IB, Talluri S, Nasir F, Kaluski E
The significance of adding new oral anticoagulants (NOACs) to antiplatelet therapy in patients with acute coronary syndrome (ACS) is unclear. We conducted a meta-analysis to assess the safety and efficacy of adding NOACs (apixaban, rivaroxaban, and dabigatran) to single antiplatelet agent (SAP) or dual antiplatelet therapy (DAPT) in patients with ACS. Seven randomized controlled trials were selected using PubMed or MEDLINE, Scopus, and Cochrane library (inception to August 2017). The summary measure was random effects hazard ratio (HR) with 95% confidence interval (CI). The primary safety outcome was clinically significant bleeding. The secondary efficacy outcome was major adverse cardiovascular events (MACE; composite of myocardial infarction, stroke, and all-cause mortality). In 31,574 patients, addition of NOAC to SAP did not increase the risk of clinically significant bleeding (HR 0.82, 95% CI 0.56 to 1.20, p = 0.31); however, the risk of clinically significant bleeding was significantly increased with NOAC plus DAPT (HR 2.24, 95% CI 1.75 to 2.87, p < 0.001). NOACs had no statistically beneficial effect on MACE when used with SAP (HR 0.82, 95% CI 0.66 to 1.04, p = 0.10); however, a modest reduction in MACE was observed when NOACs were combined with DAPT (HR 0.86, 95% CI 0.78 to 0.93, p < 0.001). In conclusion, in patients with ACS, the addition of NOAC to DAPT resulted in increased risk of clinically significant bleeding, whereas only a modest reduction in MACE was achieved. The addition of NOACs to SAP did not result in significant reduction of MACE or increase in clinically significant bleeding.

Am J Cardiol: 31 Jan 2018; 121:301-307
Khan SU, Arshad A, Riaz IB, Talluri S, Nasir F, Kaluski E
Am J Cardiol: 31 Jan 2018; 121:301-307 | PMID: 29195825
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Abstract

Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program).

Gaudet D, Watts GF, Robinson JG, Minini P, ... Louie MJ, Raal FJ
Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a).

Am J Cardiol: 28 Oct 2016; epub ahead of print
Gaudet D, Watts GF, Robinson JG, Minini P, ... Louie MJ, Raal FJ
Am J Cardiol: 28 Oct 2016; epub ahead of print | PMID: 27793396
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Abstract

Prognostic Significance of Ischemic Mitral Regurgitation on Outcomes in Acute ST-Elevation Myocardial Infarction Managed by Primary Percutaneous Coronary Intervention.

Mentias A, Raza MQ, Barakat AF, Hill E, ... Tuzcu EM, Kapadia SR
Ischemic mitral regurgitation (IMR) has been associated with worse outcome myocardial infarction. However, severity of mitral regurgitation (MR) and its impact on patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) remains unknown. We sought to determine impact of increasing severity of IMR on outcomes in patients with STEMI undergoing primary PCI. All patients presenting with STEMI who underwent primary PCI within 12 hours of symptoms from 1994 to 2014 were included. IMR was graded from 0 to 4+ within 3 days of index myocardial infarction by echocardiography. Overall, 4,005 patients with STEMI were included. None, 1+, 2+, 3+, and 4+ MR were present in 3,200 (79.9%), 427 (10.7%), 260 (6.5%), 91 (2.3%), and 27 (0.7%) patients, respectively. On multivariate logistic regression analysis, more severe MR was associated with older age, female gender, lower body mass index, anemia, inferior STEMI, and longer door-to-balloon time. The 30-day mortality rates were 6.8%, 7.3%, 8.8%, 19.8%, and 26.1%, respectively, with increasing grade of MR. The 1-year mortality rates were 10.8%, 12.4%, 20.8%, 37.4%, and 37.1%, whereas 5-year mortality rates were 16.2%, 23.1%, 36.5%, 53.8%, and 63%, respectively (p <0.001 all), for none to 4+ MR. After adjusting for age, gender, co-morbidities, ejection fraction, and shock by multivariate analysis, severity of IMR was associated with incremental effect on long-term mortality (hazard ratios of 1.42, 1.83, 2.41, and 2.95 for 1+ to 4+ MR respectively, p <0.01 for all). In conclusion, higher grades of MR in patients with STEMI undergoing primary PCI are associated with worse short- and long-term outcomes.

Am J Cardiol: 28 Oct 2016; epub ahead of print
Mentias A, Raza MQ, Barakat AF, Hill E, ... Tuzcu EM, Kapadia SR
Am J Cardiol: 28 Oct 2016; epub ahead of print | PMID: 27793397
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Abstract

Assessment of Progressive Pathophysiology After Early Prenatal Diagnosis of the Ebstein Anomaly or Tricuspid Valve Dysplasia.

Selamet Tierney ES, McElhinney DB, Freud LR, Tworetzky W, ... Silverman NH, Moon-Grady AJ
In fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD), poor hemodynamic status is associated with worse neonatal outcome. It is not known whether EA/TVD fetuses with more favorable physiology earlier in gestation progress to more severe disease in the third trimester. We evaluated if echocardiographic indexes in EA/TVD fetuses presenting <24 weeks of gestation are reliable indicators of physiologic status later in pregnancy. This multicenter, retrospective study included 51 fetuses presenting at <24 weeks of gestation with EA/TVD and serial fetal echocardiograms ≥4 weeks apart. We designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, left ventricular (LV) dysfunction, or tricuspid valve (TV) annulus Z-score >5.6. Median gestational age at diagnosis was 21 weeks (range, 18 to 24). Eighteen fetuses (35%) had no markers for poor hemodynamic status initially, whereas only 7 of these continued to have no markers of poor outcome in the third trimester. Nine of 27 fetuses (33%) with anterograde pulmonary blood flow on the first echocardiogram developed pulmonary atresia; 7 of 39 (18%) developed new pulmonary valve regurgitation. LV dysfunction was present in 2 (4%) patients at <24 weeks but in 14 (37%) later (p <0.001). The TV annulus Z-score and cardiothoracic area both increased from diagnosis to follow-up. In conclusion, progressive hemodynamic compromise was common in this cohort. Our study highlights that care must be taken in counseling before 24 weeks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring.

Am J Cardiol: 28 Oct 2016; epub ahead of print
Selamet Tierney ES, McElhinney DB, Freud LR, Tworetzky W, ... Silverman NH, Moon-Grady AJ
Am J Cardiol: 28 Oct 2016; epub ahead of print | PMID: 27793395
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Abstract

Relation of Left Atrial Size to Atrial Fibrillation in Patients Aged ≤22 Years.

Mah DY, Shakti D, Gauvreau K, Colan SD, ... Abrams DJ, Brown DW
Left atrial (LA) dilation has been shown to be associated with atrial fibrillation (AF) in the adult population, with some studies indicating that larger LAs are more prone to AF recurrence. The relation of LA size to AF in the pediatric and young adult population has not been investigated. In this study, all pediatric patients (aged ≤22 years) who presented to Boston Children\'s Hospital from January 2002 to December 2012 with AF were reviewed. Patients with significant congenital heart disease, cardiomyopathies, proven channelopathies, previous cardiac surgery, end-stage renal disease, or severe lung disease/cystic fibrosis were excluded. LA measurements were taken using the echocardiogram performed at the initial presentation. In total, 48 patients with AF were identified. The median age at presentation was 17.1 years (range 3.7 to 22.9 years); 38 patients (79%) were men. Eleven patients (23%) had at least 1 recurrence of their AF. There was no difference in body mass index, prevalence of systemic hypertension, alcohol, stimulant, or illicit drug use between those who had an isolated episode of AF and those who had a recurrence. There was no significant difference in LA dimension Z-scores between groups, with only 2 patients (1 isolated AF, 1 recurrent AF) having Z-scores >2. In conclusion, AF in the young without underlying heart disease is not associated with LA dilation.

Am J Cardiol: 25 Oct 2016; epub ahead of print
Mah DY, Shakti D, Gauvreau K, Colan SD, ... Abrams DJ, Brown DW
Am J Cardiol: 25 Oct 2016; epub ahead of print | PMID: 27780555
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Abstract

Causes and Predictors of Death in Patients With Coronary Heart Disease (from the Heart and Soul Study).

Wang EY, Dixson J, Schiller NB, Whooley MA
Although the prevalence of coronary heart disease (CHD) in the United States has increased during the past 25 years, cardiovascular mortality has decreased due to advances in CHD therapy and prevention. We sought to determine the proportion of patients with CHD who die from cardiovascular versus noncardiovascular causes and the causes and predictors of death, in a cohort of patients with CHD. The Heart and Soul Study enrolled 1,024 participants with stable CHD from 2000 to 2002 and followed them for 10 years. Causes of mortality were assigned based on detailed review of medical records, death certificates, and coroner reports by blinded adjudicators. During 7,680 person-years of follow-up, 401 participants died. Of these deaths, 42.4% were cardiovascular and 54.4% were noncardiovascular. Myocardial infarction, stroke, and sudden death accounted for 72% of cardiovascular deaths. Cancer, pneumonia, and sepsis accounted for 67% of noncardiovascular deaths. Independent predictors of cardiac mortality were older age, inducible ischemia on stress echocardiography, higher heart rate at rest, smoking, lower hemoglobin, and higher N-terminal pro-brain natriuretic peptide (all p values <0.05); independent predictors of noncardiac mortality included older age, inducible ischemia, higher heart rate, lower exercise capacity, and nonuse of statins (all p values <0.05). In conclusion, mortality in this cohort was more frequently due to noncardiovascular causes, and predictors of noncardiovascular mortality included factors traditionally associated with cardiovascular mortality.

Am J Cardiol: 27 Oct 2016; epub ahead of print
Wang EY, Dixson J, Schiller NB, Whooley MA
Am J Cardiol: 27 Oct 2016; epub ahead of print | PMID: 27788932
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Abstract

Frequency of Cardiac Death and Stent Thrombosis in Patients With Chronic Obstructive Pulmonary Disease Undergoing Percutaneous Coronary Intervention (from the BASKET-PROVE I and II Trials).

Jatene T, Biering-Sørensen T, Nochioka K, Mangione FM, ... Galatius S, BASKET-PROVE Investigators
Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death after percutaneous coronary intervention with bare-metal stents. Regarding other outcomes, previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not well known. We analyzed 4,605 patients who underwent percutaneous coronary intervention with bare-metal stents (33.1%) or DES (66.9%) from the Basel Stent Kosten-Effektivitats Trial-Prospective Validation Examination trials I and II. COPD patients (n = 283, 6.1%), were older and had more frequently a smoking or cardiovascular event history. At 2-year follow-up, cumulative event rates for patients with versus without COPD were the following: major adverse cardiac events (MACE: composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization): 15.2% versus 8.1% (p <0.001); all-cause death: 11.7% versus 2.4% (p <0.001); cardiac death: 5.7% versus 1.2% (p <0.001); myocardial infarction: 3.5% versus 1.9% (p = 0.045); definite/probable/possible stent thrombosis: 2.5% versus 0.9% (p = 0.01); and major bleeding: 4.2% versus 2.1% (p = 0.014). After adjusting for confounders including smoking status, COPD remained an independent predictor for MACE (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.31 to 2.49), all-cause death (HR 3.62, 95% CI 2.41 to 5.45), cardiac death (HR 3.12, 95% CI 1.74 to 5.60), and stent thrombosis (HR 2.39, 95% CI 1.03 to 5.54). We did not find evidence of an interaction between COPD and DES implantation (p for interaction = 0.29) for MACE. In conclusion, COPD is associated with increased 2-year rates of all-cause death, cardiac death, and stent thrombosis after stent implantation. DES use appears to be beneficial also in patients with COPD.

Am J Cardiol: 27 Oct 2016; epub ahead of print
Jatene T, Biering-Sørensen T, Nochioka K, Mangione FM, ... Galatius S, BASKET-PROVE Investigators
Am J Cardiol: 27 Oct 2016; epub ahead of print | PMID: 27788931
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Abstract

Impact of Iron Deficiency on Response to and Remodeling After Cardiac Resynchronization Therapy.

Martens P, Verbrugge F, Nijst P, Dupont M, Tang WH, Mullens W
Iron deficiency is prevalent in heart failure with reduced ejection fraction and relates to symptomatic status, readmission, and all-cause mortality. The relation between iron status and response to cardiac resynchronization therapy (CRT) remains insufficiently elucidated. This study assesses the impact of iron deficiency on clinical response and reverse cardiac remodeling and outcome after CRT. Baseline characteristics, change in New York Heart Association functional class, reverse cardiac remodeling on echocardiography, and clinical outcome (i.e., all-cause mortality and heart failure readmissions) were retrospectively evaluated in consecutive CRT patients who had full iron status and complete blood count available at implantation, implanted at a single tertiary care center with identical dedicated multidisciplinary CRT follow-up from October 2008 to August 2015. A total of 541 patients were included with mean follow-up of 38 ± 22 months. Prevalence of iron deficiency was 56% at implantation. Patients with iron deficiency exhibited less symptomatic improvement 6 months after implantation (p value <0.001). In addition, both the decrease in left ventricular end-diastolic diameter (-3.1 vs -6.2 mm; p value = 0.011) and improvement in ejection fraction (+11% vs +15%, p value = 0.001) were significantly lower in patients with iron deficiency. Iron deficiency was significantly associated with an increased risk for heart failure admission or all-cause mortality (adjusted hazard ratio 1.718, 95% confidence interval 1.178 to 2.506), irrespectively of the presence of anemia (Hemoglobin <12 g/dl in women and <13 g/dl in men). In conclusion, iron deficiency is prevalent and affects both clinical response and reverse cardiac remodeling after CRT implantation. Moreover, it is a powerful predictor of adverse clinical outcomes in CRT.

Am J Cardiol: 25 Oct 2016; epub ahead of print
Martens P, Verbrugge F, Nijst P, Dupont M, Tang WH, Mullens W
Am J Cardiol: 25 Oct 2016; epub ahead of print | PMID: 27780556
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Abstract

Risk of Aortic Dissection in Pregnant Patients With the Marfan Syndrome.

Kuperstein R, Cahan T, Yoeli-Ullman R, Ben Zekry S, Shinfeld A, Simchen MJ
Patients with Marfan syndrome (MS) face a high risk of aortic dissection during pregnancy. A dilated aortic root (>40 to 45 mm) is considered a relative contraindication for pregnancy. We investigated the risk for aortic dissection and pregnancy outcome in patients with MS. Women with MS who attended our cardiology high-risk pregnancy clinic from 2006 to 2015 were followed clinically and with serial echocardiograms by a multidisciplinary team. Beta blockers were offered and titrated by blood pressure and heart rate. Patients with aortic root dilation ≥40 mm were considered high-risk patients with MS. A consistent increase in aortic root diameter of >1 mm during pregnancy was classified as dilation during pregnancy; 31 pregnancies in 19 patients with MS were followed. Four pregnancies were terminated early because of prenatal diagnosis of fetal MS and 4 additional babies born with MS. Eight pregnancies were in patients with a dilated aortic root (40 to 46 mm); 21 patients (68%) were treated with β blockers. There were 2 cases of postpartum aortic dissection (6.5%): 1 type A dissection in a woman with a dilated aortic root who declined β blockers (1 of 8, 12.5%) and 1 type B dissection. Increasing aortic root diameter (>1 mm) in pregnancy was significantly associated with later aortic dissection (2 of 6 vs 0 of 21, p = 0.04). No maternal deaths occurred. All high-risk women with MS gave birth by cesarean section, whereas in the non-high-risk group mode of delivery was by obstetric indication. Preterm delivery rate was 41% (11 of 27). One antenatal fetal death and no major neonatal morbidity or mortality were observed. In conclusion, pregnant patients with MS, especially those with a dilating aortic root, are at high risk of aortic dissection, even with tight control of blood pressure and heart rate.

Am J Cardiol: 27 Oct 2016; epub ahead of print
Kuperstein R, Cahan T, Yoeli-Ullman R, Ben Zekry S, Shinfeld A, Simchen MJ
Am J Cardiol: 27 Oct 2016; epub ahead of print | PMID: 27788933
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Abstract

Meta-Analysis of Outcomes and Evolution of Pulmonary Hypertension Before and After Transcatheter Aortic Valve Implantation.

Tang M, Liu X, Lin C, He Y, ... Yu Y, Wang J
Pulmonary hypertension (PH) is a common entity in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI), but its role on clinical outcomes remains undetermined. We evaluated the impact of baseline and postprocedural PH on clinical outcomes and changes in pulmonary artery systolic pressure after TAVI by performing a meta-analysis of 16 studies enrolling 9,204 patients with AS who underwent TAVI. In patients with baseline PH, all-cause mortality was significantly increased, as shown by pooled odds ratio (ORs) for overall 30-day (OR 1.52, 95% confidence interval [CI] 1.28 to 1.80), 1-year (OR 1.39, 95% CI 1.27 to 1.51), and 2-year all-cause mortality (OR 2.00, 95% CI 1.49 to 2.69), compared with those without PH, independent of different methods of PH assessment. The presence of post-TAVI PH was associated with a significant increase in 2-year all-cause mortality (OR 2.32, 95% CI 1.43 to 3.74). Nevertheless, pulmonary artery systolic pressure decreased at 3-month to 1-year follow-up (standardized mean difference -1.12, 95% CI -1.46 to -0.78). Baseline PH was associated with higher 30-day and 1-year cardiovascular mortality. Patients with baseline PH had higher risk of stroke at 1 year and acute kidney injury at 30 days. But the risk of major vascular complications was significantly lower in patients with baseline PH. In conclusion, the presence of PH is associated with increased short- and long-term mortality, also higher risk of stroke and acute kidney injury after TAVI. A significant decrease in PSAP is detected in patients with AS in midterm follow-up after TAVI.

Am J Cardiol: 27 Oct 2016; epub ahead of print
Tang M, Liu X, Lin C, He Y, ... Yu Y, Wang J
Am J Cardiol: 27 Oct 2016; epub ahead of print | PMID: 27788934
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Abstract

Relation of Erectile Dysfunction to Subclinical Myocardial Injury.

Omland T, Randby A, Hrubos-Strøm H, Røsjø H, Einvik G
The circulating concentration of cardiac troponin I (cTnI) is an index of subclinical myocardial injury in several patient populations and in the general population. Erectile dysfunction is associated with greater risk for cardiovascular events, but the association with subclinical myocardial injury is not known. We aimed to test the hypothesis that the presence and severity of erectile dysfunction is associated with greater concentrations of cTnI in the general population. The presence and severity of erectile dysfunction was assessed by administering the International Index of Erectile Function 5 (IIEF-5) questionnaire to 260 men aged 30 to 65 years recruited from a population-based study. Concentrations of cTnI were determined by a high-sensitivity (hs) assay. Hs-cTnI levels were significantly higher in subjects with than in those without erectile dysfunction (median 2.9 vs 1.6 ng/l; p <0.001). Men with erectile dysfunction (i.e., IIEF-5 sum score <22) were also significantly older; had a higher systolic blood pressure, lower estimated glomerular filtration rate, higher augmentation index and N-terminal pro-B-type natriuretic peptide; and had a higher prevalence of hypertension, diabetes mellitus, and previous coronary artery disease than subjects without erectile dysfunction. These covariates were adjusted for in a multivariate linear regression model, yet the IIEF-5 sum score remained significantly negatively associated with the hs-cTnI concentration (standardized β -0.206; p <0.001). In conclusion, the presence and severity of erectile dysfunction is associated with circulating concentrations of hs-cTnI, indicating subclinical myocardial injury independently of cardiovascular risk factors, endothelial dysfunction and heart failure biomarkers.

Am J Cardiol: 25 Oct 2016; epub ahead of print
Omland T, Randby A, Hrubos-Strøm H, Røsjø H, Einvik G
Am J Cardiol: 25 Oct 2016; epub ahead of print | PMID: 27780552
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Abstract

Usefulness of Fragmented QRS Complexes in Patients With Congenital Heart Disease to Predict Ventricular Tachyarrhythmias.

Vogels RJ, Teuwen CP, Ramdjan TT, Evertz R, ... Bogers AJ, de Groot NM
Fragmented QRS complexes (fQRS) on 12-lead electrocardiogram are known predictors of ventricular tachyarrhythmia (VTA) in patients with coronary artery disease. There is limited knowledge of the clinical implications of fQRS in patients with congenital heart defects (CHD). Aims of this study were to examine (1) the occurrence of fQRS in patients with various types of CHD and (2) whether fQRS is associated with development of VTA. This study was designed as retrospective case-control study. Patients with CHD with VTA were included and matched with control patients of the same age, gender, and CHD type. Clinical data and fQRS were analyzed and compared. The initial VTA episode developed in 139 patients with CHD at a mean age of 39 ± 14 years. Compared with controls (n = 219, age 38 ± 13 years), QRS duration was longer in patients with VTA (110 vs 100 ms; p <0.01). Furthermore, fQRS was more frequently observed in patients with VTA in the last electrocardiogram before VTA (n = 73 [53%] vs n = 67 [31%]; p <0.001), especially in patients with sustained VTA (64%). Multiple conditional logistic regression demonstrated more fQRS (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5 to 5.8; p = 0.002), nonsystemic ventricular dysfunction (OR 5.1, 95% CI 2.1 to 12.4; p <0.001), and more prolonged QRS complexes (OR 2.8, 95% CI 1.3 to 6.2; p = 0.011) in patients with VTA. Therefore, the presence of fQRS on electrocardiogram may be a useful tool in daily clinical practice to identify patients at risk for developing VTA in patients with CHD, in addition to known predictors of VTA.

Am J Cardiol: 25 Oct 2016; epub ahead of print
Vogels RJ, Teuwen CP, Ramdjan TT, Evertz R, ... Bogers AJ, de Groot NM
Am J Cardiol: 25 Oct 2016; epub ahead of print | PMID: 27780553
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Abstract

Benefits of Heart Rate Slowing With Ivabradine in Patients With Systolic Heart Failure and Coronary Artery Disease.

Borer JS, Deedwania PC, Kim JB, Böhm M
Heart rate (HR) is a risk factor in patients with chronic systolic heart failure (HF) that, when reduced, provides outcome benefits. It is also a target for angina pectoris prevention and a risk marker in chronic coronary artery disease without HF. HR can be reduced by drugs; however, among those used clinically, only ivabradine reduces HR directly in the sinoatrial nodal cells without other known effects on the cardiovascular system. This review provides current information regarding the safety and efficacy of HR reduction with ivabradine in clinical studies involving >36,000 patients with chronic stable coronary artery disease and >6,500 patients with systolic HF. The largest trials, Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Disease and Left Ventricular Dysfunction and Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease, showed no effect on outcomes. The Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial, a randomized controlled trial in >6,500 patients with HF, revealed marked and significant HR-mediated reduction in cardiovascular mortality or HF hospitalizations while improving quality of life and left ventricular mechanical function after treatment with ivabradine. The adverse effects of ivabradine predominantly included bradycardia and atrial fibrillation (both uncommon) and ocular flashing scotomata (phosphenes) but otherwise were similar to placebo. In conclusion, ivabradine improves outcomes in patients with systolic HF; rates of overall adverse events are similar to placebo.

Am J Cardiol: 25 Oct 2016; epub ahead of print
Borer JS, Deedwania PC, Kim JB, Böhm M
Am J Cardiol: 25 Oct 2016; epub ahead of print | PMID: 27780557
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Abstract

Classification and Prognostic Evaluation of Left Ventricular Remodeling in Patients With Asymptomatic Heart Failure.

Pugliese NR, Fabiani I, La Carrubba S, Conte L, ... Di Bello V, Italian Society of Cardiovascular Echography (SIEC)
Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 ± 13 years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction <50%) and 483 diastolic dysfunction. According to the CRC, 891 patients were normals or presented with physiologic hypertrophy, 273 concentric remodeling, 47 eccentric remodeling, 350 concentric hypertrophy, 29 mixed hypertrophy, 86 dilated hypertrophy, and 53 eccentric hypertrophy. Age and gender distribution was noticed (p <0.001). After a median follow-up of 21 months, Kaplan-Meier analysis showed different survival distribution (p <0.001) of the CRC patterns. In multivariate Cox regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification, systolic, and diastolic dysfunction), CRC was independent predictor of primary end point (p = 0.044, hazard ratio 1.101, 95% CI 1.003 to 1.21), confirmed in a logistic regression (p <0.03). In conclusion, CRC could help physicians in prognostic stratification of patients in stage A and B HF.

Am J Cardiol: 24 Oct 2016; epub ahead of print
Pugliese NR, Fabiani I, La Carrubba S, Conte L, ... Di Bello V, Italian Society of Cardiovascular Echography (SIEC)
Am J Cardiol: 24 Oct 2016; epub ahead of print | PMID: 27776801
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Abstract

Influence of Myocardial Ischemia Extent on Left Ventricular Global Longitudinal Strain in Patients After ST-Segment Elevation Myocardial Infarction.

Dimitriu-Leen AC, Scholte AJ, Katsanos S, Hoogslag GE, ... Bax JJ, Delgado V
Two-dimensional echocardiographic left ventricular (LV) global longitudinal strain (GLS) after ST-segment elevation myocardial infarction (STEMI) is moderately correlated with infarct size and reflects the residual LV systolic function. This correlation may be influenced by the presence of myocardial ischemia. The present study investigated how myocardial ischemia modulates the correlation between LV GLS and infarct size determined with single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with first STEMI treated with primary coronary intervention. A total of 1,128 patients (age 60 ± 11 years) who underwent SPECT MPI for the evaluation of infarct size and residual ischemia were evaluated. LV GLS was measured on transthoracic echocardiography. The time interval between echocardiography and SPECT MPI was 1 ± 1 month. A moderate correlation between echocardiographic LV GLS and infarct size on SPECT MPI was observed (r = 0.58, p <0.001). This correlation was weakened by the presence or extent of ischemia; in the group of patients without ischemia, the correlation between LV GLS and infarct size on SPECT MPI was r = 0.66 (p <0.001), whereas in patients with mild or moderate-to-severe ischemia, the correlations were r = 0.56 and 0.38, respectively (both p <0.001). Moderate-to-severe myocardial ischemia was independently associated with more impaired LV GLS after adjusting for infarct size, age, diabetes mellitus, and hypertension (β 0.60, 95% confidence interval 013 to 1.06). In conclusion, the presence of myocardial ischemia after STEMI impacts on the correlation between echocardiographic LV GLS and infarct size measured on SPECT MPI. Residual ischemia is independently associated with more impaired LV GLS.

Am J Cardiol: 24 Oct 2016; epub ahead of print
Dimitriu-Leen AC, Scholte AJ, Katsanos S, Hoogslag GE, ... Bax JJ, Delgado V
Am J Cardiol: 24 Oct 2016; epub ahead of print | PMID: 27776800
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Abstract

Follow-Up of Electrocardiographic Findings and Arrhythmias in Patients With Anomalously Arising Left Coronary Artery from the Pulmonary Trunk.

Moore JA, Cabrera AG, Kim JJ, Valdés SO, de la Uz C, Miyake CY
Follow-up data and correlation of arrhythmias, electrocardiogram (ECG) changes, and cardiac function in anomalous left coronary artery from the pulmonary trunk or artery have not been previously studied. This is a retrospective single-center review of 44 anomalous left coronary artery from the pulmonary trunk or artery patients diagnosed between 1992 and 2014, at a median age of 3 months (3 days to 13 years). Clinical history, ECG, Holter, and echocardiogram data were reviewed. ECGs were reviewed for contiguous Q-or T-wave inversions, hypertrophy, bundle branch block, and axis deviation. High-grade ventricular ectopy, supraventricular tachycardia (SVT), and ventricular tachycardia (VT) were recorded. Patients with <6 months of clinical follow-up were excluded from longitudinal analysis. At diagnosis, 43 (98%) were noted to have electrocardiographic changes. During hospitalization, arrhythmias were seen in 13 patients (30%): 2 (5%) with sustained VT or ventricular fibrillation, 6 (17%) with high-grade ventricular ectopy, and 4 (9%) with SVT. Seven patients (16%) required antiarrhythmic treatment. During outpatient follow-up, arrhythmias were seen in 11 patients. New arrhythmias were documented in 6 without a history of in-hospital arrhythmias. Of 34 patients with at least 6 months follow-up (median 6 years, 0.5 to 20 years), 20 had left ventricular (LV) dysfunction before surgery. Normalization of function occurred in 94% (median 1 year, 5 days to 4 years). Electrocardiographic changes persisted in 94% at the time of LV function recovery. In conclusion, electrocardiographic changes and arrhythmias may persist despite recovery of ventricular function. Therefore, prolonged myocardial remodeling may continue even after resolution of LV dysfunction during which time arrhythmias may occur.

Am J Cardiol: 23 Oct 2016; epub ahead of print
Moore JA, Cabrera AG, Kim JJ, Valdés SO, de la Uz C, Miyake CY
Am J Cardiol: 23 Oct 2016; epub ahead of print | PMID: 27772664
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Abstract

Percutaneous Coronary Intervention as a Trigger for Stroke.

Varmdal T, Janszky I, Bakken IJ, Ellekjær H, ... Håberg SE, Bønaa KH
Percutaneous coronary intervention (PCI) is a plausible triggering factor for stroke, yet the magnitude of this excess risk remains unclear. This study aimed to quantify the transient change in risk of stroke for up to 12 weeks after PCI. We applied the case-crossover method, using data from the Norwegian Patient Register on all hospitalizations in Norway in the period of 2008 to 2014. The relative risk (RR) of ischemic stroke was highest during the first 2 days after PCI (RR 17.5, 95% confidence interval [CI] 4.2 to 72.8) and decreased gradually during the following weeks. The corresponding RR was 2.0 (95% CI 1.2 to 3.3) 4 to 8 weeks after PCI. The RR for women was more than twice as high as for men during the first 4 postprocedural weeks, RR 10.5 (95% CI 3.8 to 29.3) and 4.4 (95% CI 2.7 to 7.2), respectively. Our results were compatible with an increased RR of hemorrhagic stroke 4 to 8 weeks after PCI, but the events were few and the estimates were very imprecise, RR 3.0 (95% CI 0.8 to 11.1). The present study offers new knowledge about PCI as a trigger for stroke. Our estimates indicated a substantially increased risk of ischemic stroke during the first 2 days after PCI. The RR then decreased gradually but stayed elevated for 8 weeks. Increased awareness of this vulnerable period after PCI in clinicians and patients could contribute to earlier detection and treatment for patients suffering a postprocedural stroke.

Am J Cardiol: 24 Oct 2016; epub ahead of print
Varmdal T, Janszky I, Bakken IJ, Ellekjær H, ... Håberg SE, Bønaa KH
Am J Cardiol: 24 Oct 2016; epub ahead of print | PMID: 27776798
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Abstract

Comparison of Ambulatory, High-Dose, Intravenous Diuretic Therapy to Standard Hospitalization and Diuretic Therapy for Treatment of Acute Decompensated Heart Failure.

Buckley LF, Seoane-Vazquez E, Cheng JW, Aldemerdash A, ... Stevenson LW, Desai AS
Innovative treatment strategies for decompensated heart failure (HF) are required to achieve cost savings and improvements in outcomes. We developed a decision analytic model from a hospital perspective to compare 2 strategies for the treatment of decompensated HF, ambulatory diuretic infusion therapy, and hospitalization (standard care), with respect to total HF hospitalizations and costs. The ambulatory diuretic therapy strategy included outpatient treatment with high doses of intravenous loop diuretics in a specialized HF unit whereas standard care included hospitalization for intravenous loop diuretic therapy. Model probabilities were derived from the outcomes of patients who were treated for decompensated HF at Brigham and Women\'s Hospital (Boston, MA). Costs were based on Centers for Medicare and Medicaid reimbursement and the available reports. Based on a sample of patients treated at our institution, the ambulatory diuretic therapy strategy was estimated to achieve a significant reduction in total HF hospitalizations compared with standard care (relative reduction 58.3%). Under the base case assumptions, the total cost of the ambulatory diuretic therapy strategy was $6,078 per decompensation episode per 90 days compared with $12,175 per 90 days with standard care, for a savings of $6,097. The cost savings associated with the ambulatory diuretic strategy were robust against variation up to 50% in costs of ambulatory diuretic therapy and the likelihood of posttreatment hospitalization. An exploratory analysis suggests that ambulatory diuretic therapy is likely to remain cost saving over the long-term. In conclusion, this decision analytic model demonstrates that ambulatory diuretic therapy is likely to be cost saving compared with hospitalization for the treatment of decompensated HF from a hospital perspective. These results suggest that implementation of outpatient HF units that provide ambulatory diuretic therapy to well-selected subgroup of patients may result in significant reductions in health care costs while improving the care of patients across a variety of health care settings.

Am J Cardiol: 23 Oct 2016; 118:1350-1355
Buckley LF, Seoane-Vazquez E, Cheng JW, Aldemerdash A, ... Stevenson LW, Desai AS
Am J Cardiol: 23 Oct 2016; 118:1350-1355 | PMID: 27772698
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Abstract

Usefulness of Iron Deficiency Correction in Management of Patients With Heart Failure [from the Registry Analysis of Iron Deficiency-Heart Failure (RAID-HF) Registry].

Wienbergen H, Pfister O, Hochadel M, Michel S, ... Hambrecht R, RAID-HF (Registry Analysis of Iron Deficiency–Heart Failure) REGISTRY Study Group
Iron deficiency (ID) has been identified as an important co-morbidity in patients with heart failure (HF). Intravenous iron therapy reduced symptoms and rehospitalizations of iron-deficient patients with HF in randomized trials. The present multicenter study investigated the "real-world" management of iron status in patients with HF. Consecutive patients with HF and ejection fraction ≤40% were recruited and analyzed from December 2010 to October 2015 by 11 centers in Germany and Switzerland. Of 1,484 patients with HF, iron status was determined in only 923 patients (62.2%), despite participation of the centers in a registry focusing on ID and despite guideline recommendation to determine iron status. In patients with determined iron status, a prevalence of 54.7% (505 patients) for ID was observed. Iron therapy was performed in only 8.5% of the iron-deficient patients with HF; 2.6% were treated with intravenous iron therapy. The patients with iron therapy were characterized by a high rate of symptomatic HF and anemia. In conclusion, despite strong evidence of beneficial effects of iron therapy on symptoms and rehospitalizations, diagnostic and therapeutic efforts on ID in HF are low in the actual clinical practice, and the awareness to diagnose and treat ID in HF should be strongly enforced.

Am J Cardiol: 18 Oct 2016; epub ahead of print
Wienbergen H, Pfister O, Hochadel M, Michel S, ... Hambrecht R, RAID-HF (Registry Analysis of Iron Deficiency–Heart Failure) REGISTRY Study Group
Am J Cardiol: 18 Oct 2016; epub ahead of print | PMID: 27756479
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Abstract

Prognostic Significance of Right Ventricular Dysfunction in Patients With Functional Mitral Regurgitation Undergoing MitraClip.

Kaneko H, Neuss M, Weissenborn J, Butter C
Functional mitral regurgitation (MR) is common in patients with heart failure and left ventricular (LV) dysfunction. MitraClip (MC) is a novel therapeutic option for patients with high-risk MR. Similar to LV dysfunction, right ventricular dysfunction (RVD) is an important predictor of patients with heart failure. We aimed to clarify the effect of RVD on outcomes of functional MR and LV dysfunction after MC implantation. We examined 117 patients with severe functional MR and reduced LV ejection fraction (≤40%) treated with MC. RVD was defined as tricuspid annular plane systolic excursion <15 mm and was observed in 41 patients (35%). Mean age and gender were similar between patients with and without RVD. Atrial fibrillation was more common in patients with RVD. MR grades at baseline and discharge and LV ejection fraction were not different between the groups. Six months after MC implantation, responders to the N-terminal pro-B-type natriuretic peptide were less common in patients with RVD than those without (29% vs 65%, p = 0.005). Kaplan-Meier curves showed that survival rates of patients with RVD were significantly lower than those without (36.2% vs 69.6%, p = 0.008). After adjusting for covariates, RVD was still associated with all-cause mortality (hazard ratio 1.975, p = 0.042). The present study\'s results suggest that RVD is associated with worse survival of functional MR and LV dysfunction in patients undergoing MC in association with no response to N-terminal pro-B-type natriuretic peptide. The indication for MC should be carefully considered in functional MR patients with RVD.

Am J Cardiol: 21 Oct 2016; epub ahead of print
Kaneko H, Neuss M, Weissenborn J, Butter C
Am J Cardiol: 21 Oct 2016; epub ahead of print | PMID: 27769512
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Abstract

Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus.

Gurbel PA, Bliden KP, Chaudhary R, Patrick J, ... McLeod C, Tantry US
High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

Am J Cardiol: 21 Oct 2016; epub ahead of print
Gurbel PA, Bliden KP, Chaudhary R, Patrick J, ... McLeod C, Tantry US
Am J Cardiol: 21 Oct 2016; epub ahead of print | PMID: 27769511
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Abstract

Effectiveness and Safety of an Independently Run Nurse Practitioner Outpatient Cardioversion Program (2009 to 2014).

Norton L, Tsiperfal A, Cook K, Bagdasarian A, ... Shah M, Wang P
Sustained growth in the arrhythmia population at Stanford Health Care led to an independent nurse practitioner-run outpatient direct current cardioversion (DCCV) program in 2012. DCCVs performed by a medical doctor, a nurse practitioner under supervision, or nurse practitioners from 2009 to 2014 were compared for safety and efficacy. A retrospective review of the electronic medical records system (Epic) was performed on biodemographic data, cardiovascular risk factors, medication history, procedural data, and DCCV outcomes. A total of 869 DCCVs were performed on 557 outpatients. Subjects were largely men with an average age of 65 years; 1/3 were obese; most had atrial fibrillation; and majority of subjects were on warfarin. The success rate of the DCCVs was 93.4% (812 of 869) with no differences among the groups. There were no short-term complications: stroke, myocardial infarction, or death. The length of stay was shortest in the NP group compared to the other groups (p <0.001). In conclusion, the success rate of DCCV in all groups was extremely high, and there were no complications in any of the DCCV groups.

Am J Cardiol: 22 Oct 2016; epub ahead of print
Norton L, Tsiperfal A, Cook K, Bagdasarian A, ... Shah M, Wang P
Am J Cardiol: 22 Oct 2016; epub ahead of print | PMID: 27771002
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Abstract

Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by (13)N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy.

Yalçin H, Valenta I, Yalçin F, Corona-Villalobos C, ... Schindler TH, Abraham MR
Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using (13)NH3-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolumestress/LVvolumerest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E\', late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation(+) patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0 ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; p = 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation(+) patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation(+) vs 1.09 ± 0.39, LV cavity dilation(-); p <0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.

Am J Cardiol: 22 Oct 2016; epub ahead of print
Yalçin H, Valenta I, Yalçin F, Corona-Villalobos C, ... Schindler TH, Abraham MR
Am J Cardiol: 22 Oct 2016; epub ahead of print | PMID: 27771003
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Abstract

Effect of Beta-Blocker Therapy, Maximal Heart Rate, and Exercise Capacity During Stress Testing on Long-Term Survival (from The Henry Ford Exercise Testing Project).

Hung RK, Al-Mallah MH, Whelton SP, Michos ED, ... Keteyian SJ, Blaha MJ
Whether lower heart rate thresholds (defined as the percentage of age-predicted maximal heart rate achieved, or ppMHR) should be used to determine chronotropic incompetence in patients on beta-blocker therapy (BBT) remains unclear. In this retrospective cohort study, we analyzed 64,549 adults without congestive heart failure or atrial fibrillation (54 ± 13 years old, 46% women, 29% black) who underwent clinician-referred exercise stress testing at a single health care system in Detroit, Michigan from 1991 to 2009, with median follow-up of 10.6 years for all-cause mortality (interquartile range 7.7 to 14.7 years). Using Cox regression models, we assessed the effect of BBT, ppMHR, and estimated exercise capacity on mortality, with adjustment for demographic data, medical history, pertinent medications, and propensity to be on BBT. There were 9,259 deaths during follow-up. BBT was associated with an 8% lower adjusted achieved ppMHR (91% in no BBT vs 83% in BBT). ppMHR was inversely associated with all-cause mortality but with significant attenuation by BBT (per 10% ppMHR HR: no BBT: 0.80 [0.78 to 0.82] vs BBT: 0.89 [0.87 to 0.92]). Patients on BBT who achieved 65% ppMHR had a similar adjusted mortality rate as those not on BBT who achieved 85% ppMHR (p >0.05). Estimated exercise capacity further attenuated the prognostic value of ppMHR (per-10%-ppMHR HR: no BBT: 0.88 [0.86 to 0.90] vs BBT: 0.95 [0.93 to 0.98]). In conclusion, the prognostic value of ppMHR was significantly attenuated by BBT. For patients on BBT, a lower threshold of 65% ppMHR may be considered for determining worsened prognosis. Estimated exercise capacity further diminished the prognostic value of ppMHR particularly in patients on BBT.

Am J Cardiol: 26 Sep 2016; epub ahead of print
Hung RK, Al-Mallah MH, Whelton SP, Michos ED, ... Keteyian SJ, Blaha MJ
Am J Cardiol: 26 Sep 2016; epub ahead of print | PMID: 27670797
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Abstract

Pooled Analysis Comparing the Efficacy of Intracoronary Versus Intravenous Abciximab in Smokers Versus Nonsmokers Undergoing Primary Percutaneous Coronary Revascularization for Acute ST-Elevation Myocardial Infarction.

Piccolo R, Galasso G, Eitel I, Dominguez-Rodriguez A, ... Thiele H, Piscione F
Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We pooled data from 5 randomized trials comparing intracoronary versus intravenous abciximab bolus in patients undergoing primary PCI. The primary end point was the composite of death or reinfarction at a mean follow-up of 292 ± 138 days. Of 3,158 participants, 1,369 (43.3%) were smokers, and they had a lower risk of the primary end point in crude, but not in adjusted analyses (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.63 to 1.21, p = 0.405). Intracoronary versus intravenous abciximab was associated with a significant reduction in the risk of primary end point among smokers (3.6% vs 8.0%; HR 0.43, 95% CI 0.26 to 0.72, p = 0.001), but not in nonsmokers (10.2% vs 9.9%; HR 0.99, 95% CI 0.72 to 1.36, p = 0.96), with a significant interaction (p = 0.009). Furthermore, intracoronary abciximab decreased the risk of reinfarction in smokers (HR 0.30, 95% CI 0.15 to 0.62, p = 0.001), with no difference in nonsmokers (HR 1.20, 95% CI 0.71 to 2.01, p = 0.50). Stent thrombosis was lowered by intracoronary abciximab in smokers (HR 0.28, 95% CI 0.06 to 0.66, p = 0.009), but was ineffective in nonsmokers (HR 1.04, 95% CI 0.54 to 2.00, p = 0.903). Interaction testing showed heterogeneity in treatment effect for reinfarction (p = 0.002) and stent thrombosis (p = 0.018) according to smoking status. In conclusion, among patients with STEMI undergoing primary PCI, smoking status did not affect the adjusted risk of clinical events. Intracoronary abciximab bolus improved clinical outcomes by reducing the risk of death or reinfarction.

Am J Cardiol: 18 Oct 2016; epub ahead of print
Piccolo R, Galasso G, Eitel I, Dominguez-Rodriguez A, ... Thiele H, Piscione F
Am J Cardiol: 18 Oct 2016; epub ahead of print | PMID: 27756477
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Abstract

Effect of Heart Rate and Use of Beta Blockers on Mortality After Heart Transplantation.

Ciarka A, Lund LH, Van Cleemput J, Voros G, Droogne W, Vanhaecke J
Heart transplantation (HT) recipients may have tachycardia secondary to cardiac denervation. As higher heart rate predicts worse outcomes in cardiovascular disease, we hypothesized that tachycardia and nonuse of β blockers are associated with increased mortality after HT. All patients who underwent HT at our institution from 1987 to 2010 were included. The association of heart rate 3 months after HT and β-blocker use during follow-up to mortality was assessed using Kaplan-Meier and multivariate Cox proportional hazards regression analyses adjusting for clinically relevant baseline variables. From 1987 to 2010, there were 493 HT. After excluding 29 who died within 3 months and 3 with follow-up <3 months, 461 HT recipients (50 ± 2 years; 20% women) were included. Over a follow-up of 12 ± 7 years, selected important univariate predictors of post-HT mortality were older age, male gender, higher body mass index, ischemic cardiomyopathy, longer post-HT intensive care unit stay, and hospitalization and at 3 months, increased mean pulmonary artery pressure, right atrial pressure and pulmonary capillary occlusion pressure, higher heart rate, and nonuse of β blockers during follow-up. In multivariate analysis, older ager, longer hospitalization, higher mean pulmonary artery pressure, higher heart rate at 3 months (hazard ratio 1.02 per beat, 95% confidence interval 1.008 to 1.035, p = 0.02) and nonuse of β blockers (hazard ratio 1.43, 95% confidence interval 1.002 to 2.031, p <0.05) were associated with mortality. In conclusion, in a large single-center cohort of HT recipients, higher heart rate and nonuse of β blockers were independently associated with higher mortality.

Am J Cardiol: 15 Oct 2016; epub ahead of print
Ciarka A, Lund LH, Van Cleemput J, Voros G, Droogne W, Vanhaecke J
Am J Cardiol: 15 Oct 2016; epub ahead of print | PMID: 27743576
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Decade-Long Trends (2001 to 2011) in the Use of Evidence-Based Medical Therapies at the Time of Hospital Discharge for Patients Surviving Acute Myocardial Infarction.

Makam RC, Erskine N, McManus DD, Lessard D, ... Yarzebski J, Goldberg RJ
Optimization of medical therapy during discharge planning is vital for improving patient outcomes after hospitalization for acute myocardial infarction (AMI). However, limited information is available about recent trends in the prescribing of evidence-based medical therapies in these patients, especially from a population-based perspective. We describe decade-long trends in the discharge prescribing of aspirin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β blockers, and statins in hospital survivors of AMI. The study population consisted of 5,253 patients who were discharged from all 11 hospitals in central Massachusetts after AMI in 6 biennial periods from 2001 to 2011. Combination medical therapy (CMT) was defined as the prescription of all 4 cardiac medications at hospital discharge. The average age of this patient population was 69.2 years and 57.7% were men. Significant increases were observed in the use of CMT, from 25.6% in 2001 to 48.7% in 2011, with increases noted for each of the individual cardiac medications examined. Subgroup analysis also showed improvement in discharge prescriptions for P2Y12 inhibitors in patients who underwent a percutaneous coronary intervention. Presence of a do-not-resuscitate order, before co-morbidities, hospitalization for non-ST-segment elevation myocardial infarction, admission to a nonteaching hospital, and failure to undergo cardiac catheterization or a percutaneous coronary intervention were associated with underuse of CMT. In conclusion, our study demonstrates encouraging trends in the prescribing of evidence-based medications at hospital discharge for AMI. However, certain patient subgroups continue to be at risk for underuse of CMT, suggesting the need for strategies to enhance compliance with current practice guidelines.

Am J Cardiol: 15 Oct 2016; epub ahead of print
Makam RC, Erskine N, McManus DD, Lessard D, ... Yarzebski J, Goldberg RJ
Am J Cardiol: 15 Oct 2016; epub ahead of print | PMID: 27743577
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Usefulness of C-Reactive Protein as a Predictor of Contrast-Induced Nephropathy After Percutaneous Coronary Interventions in Patients With Acute Myocardial Infarction and Presentation of a New Risk Score (Athens CIN Score).

Lazaros G, Zografos T, Oikonomou E, Siasos G, ... Tsalamandris S, Tousoulis D
Contrast-induced nephropathy (CIN) after percutaneous coronary interventions (PCI) in patients with acute myocardial infarction (AMI) is associated with high morbidity and mortality, whereas there are no reliable predictive tools easy to use. We evaluated the association of pre-procedural high-sensitivity C-reactive protein (hsCRP) with the development of CIN and integrated this variable in a new risk CIN prediction model. Consecutive patients (348 AMI subjects) who underwent PCI were recruited. Creatinine levels were detected on admission, at 24, 48, and 72 hours after PCI. CIN was defined using the Kidney Disease: Improving Global Outcomes criteria. In our study population (348 subjects), CIN developed in 54 patients (15.5%). Patients with CIN were older and had higher hsCRP at admission, whereas their ejection fraction (EF) and glomerular filtration rate (GFR) were lower. In multivariate analysis after incorporating potential confounders, hsCRP at admission was an independent predictor of CIN (OR for logCRP 2.00, p = 0.01). In receiver-operating characteristic curve analysis, a model incorporating hsCRP, age, GFR, and EF showed good accuracy in predicting the development of CIN (c statistic 0.84, 95% confidence interval 0.793 to 0.879). A total risk score derived from the proposed model yielded significant positive and negative predictive values and classified 85.8% of our patients correctly for CIN. In conclusion, measuring hsCRP levels at admission in patients who underwent PCI for AMI may offer additional assistance in predicting the development of CIN. A model incorporating age and admission hsCRP, EF, and GFR emerged as an accurate tool for predicting CIN in this context.

Am J Cardiol: 16 Oct 2016; epub ahead of print
Lazaros G, Zografos T, Oikonomou E, Siasos G, ... Tsalamandris S, Tousoulis D
Am J Cardiol: 16 Oct 2016; epub ahead of print | PMID: 27745963
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Abstract

Etiologies and Predictors of 30-Day Readmission and In-Hospital Mortality During Primary and Readmission After Transcatheter Aortic Valve Implantation.

Panaich SS, Arora S, Patel N, Lahewala S, ... Grines CL, Badheka AO
There are sparse data on the etiologies and predictors of readmission after transcatheter aortic valve implantation (TAVI). The study cohort was derived from the National Readmission Data 2013, a subset of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. TAVI was identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. The coprimary outcomes were 30-day readmissions and in-hospital mortality during primary admission and readmission. Hierarchical 2-level logistic models were used to evaluate study outcomes. Our analysis included 5,702 (weighted n = 12,703) TAVI procedures. About 1,215 patients were readmitted (weighted n = 2,757) within 30 days during the study year. Significant predictors of readmission included transapical access (OR, 95% CI, p value) (1.23, 1.10 to 1.38, <0.01), diabetes (1.18, 1.06 to 1.32, p 0.004), chronic lung disease (1.32, 1.18 to 1.47, <0.01), renal failure (1.43, 1.24 to 1.65, <0.01), patients discharged to facilities (1.28, 1.14 to 1.43, <0.01), and those who had lengthier hospital stays during primary admission (length of stay >10 days: 3.06, 2.22 to 4.22, <0.01). Female gender (1.39, 1.16 to 1.68, <0.01), blood transfusion (1.88, 1.55 to 2.29, <0.01), use of vasopressors (3.63, 2.50 to 5.28, <0.01), hemodynamic support (6.39, 5.20 to 7.85, <0.01) and percutaneous coronary intervention (1.89, 1.30 to 2.74, 0.01) during primary admission were significant predictors of in-hospital mortality. Age and transapical access were significant predictors of in-hospital mortality during readmission. In conclusion, heart failure, pneumonia, and bleeding complications are among important etiologies of readmission in patients after TAVI. Patients who underwent transapical TAVI and those with slower in-hospital recovery and co-morbidities such as chronic lung disease and renal failure are more likely to be readmitted to the hospital.

Am J Cardiol: 27 Sep 2016; epub ahead of print
Panaich SS, Arora S, Patel N, Lahewala S, ... Grines CL, Badheka AO
Am J Cardiol: 27 Sep 2016; epub ahead of print | PMID: 27677388
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Abstract

Prognostic Usefulness of the Ballooning Pattern in Patients With Takotsubo Cardiomyopathy.

Stiermaier T, Möller C, Graf T, Eitel C, ... Thiele H, Eitel I
The aim of the present analysis was to evaluate the prognostic impact of different ballooning patterns in patients with Takotsubo cardiomyopathy (TTC). A total of 285 consecutive patients with TTC were included. Clinical characteristics and short- and long-term outcomes were compared between patients with typical apical ballooning (n = 204) and patients with an atypical ballooning pattern including midventricular and basal ballooning (n = 81). Patients with typical apical ballooning were significantly older (73.3 ± 10.2 vs 68.4 ± 10.3 years; p <0.01) and had a higher prevalence of diabetes mellitus (25.5% vs 12.3%; p = 0.02). The initial left ventricular (LV) ejection fraction was significantly lower in case of apical ballooning (41.5 ± 10.4% vs 46.9 ± 10.9%; p <0.01) but recovered to normal values in both groups (58.4 ± 8.0 vs 59.7 ± 7.0; p = 0.25). Although 28-day mortality did not differ significantly (p = 0.10), typical apical ballooning was associated with an increased 6-month (13.4% vs 1.3%; hazard ratio [HR] 10.81, 95% confidence interval [CI] 1.47 to 79.66; p = 0.02) and long-term mortality rates (28.9% vs 14.5%; HR 2.24, 95% CI 1.17 to 4.71; p = 0.02). A landmark analysis which included only patients who survived the first 6 months after the initial event demonstrated similar mortality rates in patients with typical (17.9%) and atypical (13.3%) ballooning (HR 1.36, 95% CI 0.67 to 2.79; p = 0.40). In conclusion, in patients with TTC, typical apical ballooning is associated with more severe LV dysfunction at acute presentation and higher mortality rates within the first 6 months after the initial event. After complete recovery of LV function, prognosis is similar in patients with typical and atypical ballooning patterns.

Am J Cardiol: 26 Sep 2016; epub ahead of print
Stiermaier T, Möller C, Graf T, Eitel C, ... Thiele H, Eitel I
Am J Cardiol: 26 Sep 2016; epub ahead of print | PMID: 27670792
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Abstract

Effect of Body Mass Index on Left Ventricular Mass in Career Male Firefighters.

Korre M, Porto LG, Farioli A, Yang J, ... Smith D, Kales SN
Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD) events; increased LV mass is common among US firefighters and plays a major role in firefighter sudden cardiac death. We aim to identify significant predictors of LV mass among firefighters. Cross-sectional study of 400 career male firefighters selected by an enriched randomization strategy. Weighted analyses were performed based on the total number of risk factors per subject with inverse probability weighting. LV mass was assessed by echocardiography (ECHO) and cardiac magnetic resonance, and normalized (indexed) for height. CVD risk parameters included vital signs at rest, body mass index (BMI)-defined obesity, obstructive sleep apnea risk, low cardiorespiratory fitness, and physical activity. Linear regression models were performed. In multivariate analyses, BMI was the only consistent significant independent predictor of LV mass indexes (all, p <0.001). A 1-unit decrease in BMI was associated with 1-unit (g/m(1.7)) reduction of LV mass/height(1.7) after adjustment for age, obstructive sleep apnea risk, and cardiorespiratory fitness. In conclusion, after height-indexing ECHO-measured and cardiac magnetic resonance-measured LV mass, BMI was found to be a major driver of LV mass among firefighters. Our findings taken together with previous research suggest that reducing obesity will improve CVD risk profiles and decrease on-duty CVD and sudden cardiac death events in the fire service. Our results may also support targeted noninvasive screening for LV hypertrophy with ECHO among obese firefighters.

Am J Cardiol: 29 Sep 2016; epub ahead of print
Korre M, Porto LG, Farioli A, Yang J, ... Smith D, Kales SN
Am J Cardiol: 29 Sep 2016; epub ahead of print | PMID: 27687051
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Abstract

Symptom-Onset-To-Balloon Time, ST-Segment Resolution and In-Hospital Mortality in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention in China: From China Acute Myocardial Infarction Registry.

Song F, Yu M, Yang J, Xu H, ... Yang Y, China Acute Myocardial Infarction (CAMI) Registry study group
Animal and imaging study evidence favors early reperfusion for acute myocardial infarction. However, in clinical trials, the effect of symptom-onset-to-balloon (S2B) time on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) has been inconsistent. Moreover, there are few data regarding the ischemic time in China. A total of 3,877 consecutive patients with STEMI with available S2B time undergoing pPCI from January 2013 to September 2014 at 108 hospitals that participated in the China Acute Myocardial Infarction registry were included and stratified into 3 S2B groups: <6 hours, 6 to 12 hours, >12 hours S2B time was tested in multivariate logistic regression analyses as an independent risk factor of mortality (primary outcome), major adverse cardiovascular and cerebrovascular events (MACCE), and impaired myocardial perfusion (secondary outcomes). The median S2B time was 5.5 (3.75 to 8.50) hours. Longer S2B time was associated with higher in-hospital mortality (<6 hours: 2.7%; 6 to 12 hours: 3.4%; >12 hours: 4.9%; p = 0.047) and ST-segment resolution <50% (<6 hours: 16.7%; 6 to 12 hours: 19.2%; >12 hours: 24.3%; p = 0.002) but not MACCE. In multivariate-adjusted analysis, S2B >12 hours remained associated with ST-segment resolution <50% (odds ratio 1.53, 95% confidence interval 1.16 to 2.01, p = 0.002) but not with in-hospital mortality (odds ratio 1.673, 95% confidence interval 0.95 to 2.94, p = 0.073). In conclusion, median S2B time in patients with STEMI undergoing pPCI was longer than that in registry studies from other countries. Longer S2B time was associated with impaired myocardial perfusion but not with in-hospital mortality or MACCE.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Song F, Yu M, Yang J, Xu H, ... Yang Y, China Acute Myocardial Infarction (CAMI) Registry study group
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666173
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Abstract

Relation of Statin Use and Mortality in Community-Dwelling Frail Older Patients With Coronary Artery Disease.

Pilotto A, Gallina P, Panza F, Copetti M, ... Marchionni N, MPI_AGE Project Investigators
Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged ≥65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1, -2, and -3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and ≥85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins.

Am J Cardiol: 26 Sep 2016; epub ahead of print
Pilotto A, Gallina P, Panza F, Copetti M, ... Marchionni N, MPI_AGE Project Investigators
Am J Cardiol: 26 Sep 2016; epub ahead of print | PMID: 27670793
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Abstract

Meta-Analysis Comparing Established Risk Prediction Models (EuroSCORE II, STS Score, and ACEF Score) for Perioperative Mortality During Cardiac Surgery.

Sullivan PG, Wallach JD, Ioannidis JP
A wide variety of multivariable risk models have been developed to predict mortality in the setting of cardiac surgery; however, the relative utility of these models is unknown. This study investigated the literature related to comparisons made between established risk prediction models for perioperative mortality used in the setting of cardiac surgery. A systematic review was conducted to capture studies in cardiac surgery comparing the relative performance of at least 2 prediction models cited in recent guidelines (European System for Cardiac Operative Risk Evaluation [EuroSCORE II], Society for Thoracic Surgeons 2008 Cardiac Surgery Risk Models [STS] score, and Age, Creatinine, Ejection Fraction [ACEF] score) for the outcomes of 1-month or inhospital mortality. For articles that met inclusion criteria, we extracted information on study design, predictive performance of risk models, and potential for bias. Meta-analyses were conducted to calculate a summary estimate of the difference in AUCs between models. We identified 22 eligible studies that contained 33 comparisons among the above models. Meta-analysis of differences in AUCs revealed that the EuroSCORE II and STS score performed similarly (with a summary difference in AUC = 0.00), while outperforming the ACEF score (with summary differences in AUC of 0.10 and 0.08, respectively, p <0.05). Other metrics of discrimination and calibration were presented less consistently, and no study presented any metric of reclassification. Small sample size and absent descriptions of missing data were common in these studies. In conclusion, the EuroSCORE II and STS score outperform the ACEF score on discrimination.

Am J Cardiol: 29 Sep 2016; epub ahead of print
Sullivan PG, Wallach JD, Ioannidis JP
Am J Cardiol: 29 Sep 2016; epub ahead of print | PMID: 27687052
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Abstract

Prognostic Value of the Thrombolysis in Myocardial Infarction Risk Score in ST-Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction (from the EPHESUS Trial).

Popovic B, Girerd N, Rossignol P, Agrinier N, ... Pitt B, Zannad F
The Thrombolysis in Myocardial Infarction (TIMI) risk score remains a robust prediction tool for short-term and midterm outcome in the patients with ST-elevation myocardial infarction (STEMI). However, the validity of this risk score in patients with STEMI with reduced left ventricular ejection fraction (LVEF) remains unclear. A total of 2,854 patients with STEMI with early coronary revascularization participating in the randomized EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial were analyzed. TIMI risk score was calculated at baseline, and its predictive value was evaluated using C-indexes from Cox models. The increase in reclassification of other variables in addition to TIMI score was assessed using the net reclassification index. TIMI risk score had a poor predictive accuracy for all-cause mortality (C-index values at 30 days and 1 year ≤0.67) and recurrent myocardial infarction (MI; C-index values ≤0.60). Among TIMI score items, diabetes/hypertension/angina, heart rate >100 beats/min, and systolic blood pressure <100 mm Hg were inconsistently associated with survival, whereas none of the TIMI score items, aside from age, were significantly associated with MI recurrence. Using a constructed predictive model, lower LVEF, lower estimated glomerular filtration rate (eGFR), and previous MI were significantly associated with all-cause mortality. The predictive accuracy of this model, which included LVEF and eGFR, was fair for both 30-day and 1-year all-cause mortality (C-index values ranging from 0.71 to 0.75). In conclusion, TIMI risk score demonstrates poor discrimination in predicting mortality or recurrent MI in patients with STEMI with reduced LVEF. LVEF and eGFR are major factors that should not be ignored by predictive risk scores in this population.

Am J Cardiol: 27 Sep 2016; epub ahead of print
Popovic B, Girerd N, Rossignol P, Agrinier N, ... Pitt B, Zannad F
Am J Cardiol: 27 Sep 2016; epub ahead of print | PMID: 27677387
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Abstract

Quantification of pericardial effusions by echocardiography and computed tomography.

Leibowitz D, Perlman G, Planer D, Gilon D, Berman P, Bogot N
Echocardiography is a well-accepted tool for the diagnosis and quantification of pericardial effusion (PEff). Given the increasing use of computed tomographic (CT) scanning, more PEffs are being initially diagnosed by computed tomography. No study has compared quantification of PEff by computed tomography and echocardiography. The objective of this study was to assess the accuracy of quantification of PEff by 2-dimensional echocardiography and computed tomography compared to the amount of pericardial fluid drained at pericardiocentesis. We retrospectively reviewed an institutional database to identify patients who underwent chest computed tomography and echocardiography before percutaneous pericardiocentesis with documentation of the amount of fluid withdrawn. Digital 2-dimensional echocardiographic and CT images were retrieved and quantification of PEff volume was performed by applying the formula for the volume of a prolate ellipse, π × 4/3 × maximal long-axis dimension/2 × maximal transverse dimension/2 × maximal anteroposterior dimension/2, to the pericardial sac and to the heart. Nineteen patients meeting study qualifications were entered into the study. The amount of PEff drained was 200 to 1,700 ml (mean 674 ± 340). Echocardiographically calculated pericardial effusion volume correlated relatively well with PEff volume (r = 0.73, p <0.001, mean difference -41 ± 225 ml). There was only moderate correlation between CT volume quantification and actual volume drained (r = 0.4, p = 0.004, mean difference 158 ± 379 ml). In conclusion, echocardiography appears a more accurate imaging technique than computed tomography in quantitative assessment of nonloculated PEffs and should continue to be the primary imaging in these patients.

Am J Cardiol: 07 Jan 2011; 107:331-5
Leibowitz D, Perlman G, Planer D, Gilon D, Berman P, Bogot N
Am J Cardiol: 07 Jan 2011; 107:331-5 | PMID: 21211612
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Abstract

Serum Potassium Levels and Outcome in Patients With Chronic Heart Failure.

Hoss S, Elizur Y, Luria D, Keren A, Lotan C, Gotsman I
Potassium levels are often abnormal in patients with heart failure (HF) and have a detrimental effect on clinical outcome. We evaluated potassium levels in a real-world cohort of patients with HF and its effect on mortality. All patients with a diagnosis of HF at a health maintenance organization were evaluated and followed for cardiac-related hospitalizations and death. The cohort consisted of 6,073 patients with HF. Mean potassium levels were 4.57 ± 0.53 mmol/L. Most patients (68%) had potassium levels in the normal range (4.0 to 5.0 mmol/L). High-normal potassium levels (5.0 to 5.5) were present in 17% of the patients, low potassium levels (<4.0) in 11%, and hyperkalemia (K ≥5.5) in 4%. Mean follow-up was 576 days. The overall mortality rate during this period was 14%. Survival rate by Kaplan-Meier analysis demonstrated that hypokalemia (K ≤3.5) was associated with the lowest survival rate. Survival was highest in patients with high-normal potassium levels. Cox regression analysis after adjustment for significant predictors including co-morbidities and standard HF drug therapies demonstrated that high-normal potassium levels were independently associated with reduced mortality compared with normal reference levels (hazard ratio 0.78, 95 confidence interval [CI] 0.64 to 0.95, p = 0.01). Subgroup analysis showed improved outcome with high-normal potassium levels in patients with reduced renal function, spironolactone, and loop diuretic therapy. In conclusion, potassium levels in the high-normal range appear to be safe and are associated with an improved outcome in patients with HF.

Am J Cardiol: 10 Oct 2016; epub ahead of print
Hoss S, Elizur Y, Luria D, Keren A, Lotan C, Gotsman I
Am J Cardiol: 10 Oct 2016; epub ahead of print | PMID: 27726855
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Abstract

Meta-Analysis of Randomized Trials on the Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients ≥65 Years of Age.

Bavishi C, Ahmed M, Trivedi V, Khan AR, ... Bangalore S, Messerli FH
The comparative efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) with other agents in patients ≥65 years of age with cardiovascular diseases or at-risk are unknown. Electronic databases were systematically searched to identify all randomized controlled trials that compared ACEIs with control (placebo or active) and reported long-term cardiovascular outcomes. We required the mean age of patients in the studies to be ≥65 years. Random-effects model was used to pool study results. Sixteen trials with 104,321 patients and a mean follow-up of 2.9 years were included. Compared with placebo, ACEIs significantly reduced all outcomes except stroke. Compared with active controls, ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI 0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to 1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95% CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was similar compared with active controls. Meta-regression analysis showed that the effect of ACEIs on outcomes remained consistent with age increasing ≥65 years. Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor blockers and heart failure trials yielded similar results, except for reduction in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to active controls for mortality outcomes. Compared with placebo, there was evidence for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke and increased the risk of angioedema, hypotension, and renal failure.

Am J Cardiol: 02 Oct 2016; epub ahead of print
Bavishi C, Ahmed M, Trivedi V, Khan AR, ... Bangalore S, Messerli FH
Am J Cardiol: 02 Oct 2016; epub ahead of print | PMID: 27692594
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Abstract

Rates and Implications for Hospitalization of Patients ≥65 Years of Age With Atrial Fibrillation/Flutter.

Naccarelli GV, Johnston SS, Dalal M, Lin J, Patel PP
The responsibility of managing atrial fibrillation (AF) and atrial flutter (AFL) falls predominantly on the Medicare system. Patients with AF or AFL often have a range of cardiovascular (CV) co-morbidities and are frequently hospitalized for AF and other CV causes. The present retrospective cohort study used medical claims data to evaluate the rates of hospitalization and inpatient mortality in elderly (aged ≥65 years) patients with AF or AFL with Medicare supplemental insurance. The data were extracted from the United States Thomson Reuters MarketScan Medicare Supplemental and Coordination of Benefits Database (January 2004 to December 2007). Patients aged ≥65 years with ≥1 inpatient or ≥2 outpatient nondiagnostic claims for AF or AFL and ≥12 months of continuous enrollment before their index AF or AFL diagnoses were identified. The frequencies of hospitalization and inpatient death were evaluated over the postindex study period (mean 24.3 months). Of an eligible study population of 55,774 patients with AF or AFL (mean age 77.9 years, 52.2% men), 28,939 patients (51.9%) were hospitalized (all causes) with nonfatal outcomes, 12,652 (22.7%) were rehospitalized, and 1,592 (2.9%) died in the hospital. Higher proportions of patients were hospitalized for non-CV than for CV causes (35.6% vs 27.2%). For CV hospitalizations culminating in inpatient death (n = 516), the most common admission diagnoses were major bleeding, stroke or transient ischemic attack, and congestive heart failure. In conclusion, elderly patients with AF or AFL undergo frequent hospitalization for CV and non-CV causes. Measures that lower inpatient admission rates, particularly readmission rates, may reduce the increasing cost of treating patients with AF or AFL with Medicare supplemental insurance.

Am J Cardiol: 28 Nov 2011; epub ahead of print
Naccarelli GV, Johnston SS, Dalal M, Lin J, Patel PP
Am J Cardiol: 28 Nov 2011; epub ahead of print | PMID: 22118826
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Abstract

Prevalence and Clinical Significance of an E-Reversal Wave in the Left Ventricular Outflow Tract.

Pressman GS, Matejkova M, Horrow JC, Pai RG
Diastolic waves are commonly seen in the left ventricular outflow tract on echocardiography. This work focuses on the E-reversal wave (Er) that occurs early in diastole, shortly after the mitral E wave. Factors associated with Er presence and velocity were investigated in a broad patient sample: 100 subjects with normal ejection fraction (EF >55%) and 100 subjects with reduced EF (<45%). Er presence was noted in 58% of the total cohort and correlated inversely with age. It was more common with normal EF (70% vs 45%, p = 0.0005) and was associated with higher mitral E velocity (78.3 ± 23.3 vs 68.4 ± 19.0 cm/s; p = 0.002) and septal e\' velocity (6.7 ± 2.5 vs 5.3 ± 2.3 cm/s; p <0.0001). Er velocity was higher in the normal EF group (50 ± 18 vs 34 ± 13 cm/s, p <0.0001) and showed moderate correlation with septal e\' velocity (r = 0.43; p <0.0001); 56 subjects experienced major adverse cardiovascular events (MACE) over 1.7 ± 0.3 years of follow-up. Those with an Er had less MACE (particularly heart failure), even after adjustment for multiple clinical and echocardiographic variables (OR 0.28, 95% CI 0.11 to 0.65; p = 0.003). When stratified by EF, the association between Er presence and MACE was significant only in the low EF group. Thus, Er occurs more commonly in younger subjects and those with preserved EF. It is associated with less MACE although this effect appears to be limited to patients with reduced EF.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Pressman GS, Matejkova M, Horrow JC, Pai RG
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666176
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Abstract

Anticoagulation After Heart Valve Replacement or Transcatheter Valve Implantation.

Carnicelli AP, O\'Gara PT, Giugliano RP
Valvular heart disease is prevalent and represents a significant contributor to cardiac morbidity and mortality. Several options for valve replacement exist, including surgical replacement and transcatheter valve implantation. Prosthetic valves lead to increased risk of thromboembolic disease; therefore, antithrombotic therapy after valve replacement is indicated. For patients with mechanical prostheses, indefinite vitamin K antagonist and antiplatelet therapy are the mainstays of treatment. There is no consensus regarding optimal antithrombotic therapy after bioprosthetic valve replacement, although vitamin K antagonist therapy of varying duration in addition to antiplatelet therapy is recommended by guidelines. Dual-antiplatelet therapy is commonly used after transcatheter valve implantation; however, alternative antithrombotic regimens are being studied. Further studies are needed to identify the optimal regimen, intensity, and duration of antithrombotic therapy after surgical bioprosthetic valve replacement and transcatheter valve implantation.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Carnicelli AP, O'Gara PT, Giugliano RP
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666180
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Abstract

Impact of Renal Dysfunction on Results of Transcatheter Aortic Valve Replacement Outcomes in a Large Multicenter Cohort.

Codner P, Levi A, Gargiulo G, Praz F, ... Barsheshet A, Kornowski R
Patients with advanced chronic renal dysfunction were excluded from randomized trials of transcatheter aortic valve replacement (TAVR). The potential impact of chronic renal disease on TAVR prognosis is not fully understood. We aim to evaluate outcomes within a large cohort of patients who underwent TAVR distinguished by renal function. Baseline characteristics, procedural data, and clinical follow-up findings were collected from 10 high-volume TAVR centers in Europe, Israel, and Japan. Data were analyzed according to renal function. Patients (n = 1,204) were divided into 4 groups according to pre-TAVR-estimated glomerular filtration rate (eGFR): group I (eGFR >60), n = 288 (female 45%), group II (eGFR 31 to 60), n = 452 (female 61%), group III (eGFR ≤30), n = 398 (female 61%), and group IV (dialysis), n = 66 (female 31%). Mean Society of Thoracic Surgeons score was higher in patients with lower preprocedural eGFR. All-cause mortality at 1 year was higher in patients with lower eGFR (9.0%, 12.1%, 24.3%, and 24.2% for group I, II, III, and IV, respectively, p <0.001). Multivariate analysis demonstrated that eGFR ≤30, but not eGFR 31 to 60, was associated with increased risk of death (odds ratio 3), bleeding (odds ratio 5.2), and device implantation failure (hazard ratio 2.28). For each 10 ml/min decrease in eGFR, there was an associated relative increase in the risk of death (35%; p <0.001), cardiovascular death (14%; p = 0.018), major bleeding 35% (p <0.001), and transcatheter valve failure (16%; p = 0.007). Renal dysfunction was not associated with stroke or need for pacemaker implantation. In conclusion, among patients who underwent TAVR, baseline renal dysfunction is an important independent predictor of morbidity and mortality.

Am J Cardiol: 10 Oct 2016; epub ahead of print
Codner P, Levi A, Gargiulo G, Praz F, ... Barsheshet A, Kornowski R
Am J Cardiol: 10 Oct 2016; epub ahead of print | PMID: 27726854
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Abstract

Comparing Coronary Atheroma Progression Rates and Coronary Events in the United States, Canada, Latin America, and Europe.

Puri R, Nicholls SJ, St John J, Tuzcu EM, ... Wolski K, Nissen SE
We explored for geographic variations in coronary atheroma progression rates in the United States compared to other world regions (Canada, Latin America, Western Europe, and Central-Eastern Europe) and sought to ascertain if this associated with regional differences in major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, coronary revascularization). Across 7 randomized trials with a global recruitment pattern, 5,451 participants with angiographic coronary disease underwent serial coronary intravascular ultrasonography during 18 or 24 months, with adjudicated MACE. Change in coronary percent atheroma volume (ΔPAV) and MACE in the United States versus other world regions were assessed. Despite similar baseline angiographic and plaque characteristics across participants and regions, following propensity-weighted and multivariate analysis, US (n = 3,706) versus non-US (n = 1,745) participants demonstrated marginal but significantly greater annualized ΔPAV (least-square means ± SE: 0.27 ± 0.14% vs 0.062 ± 0.14%, p = 0.005). However, MACE rates were disproportionately higher in US compared to non-US participants (23.5% vs 10.9%, p <0.001), driven by a doubling in crude rates of coronary revascularization procedures (16.1% vs 7.8%, p <0.001). The US participants hospitalized with unstable angina demonstrated more significant disease progression than their non-US counterparts (ΔPAV: 0.57 ± 0.19% vs -0.30 ± 0.36%, p = 0.033) and greater MACE (9.1% vs 4.8%, p <0.001). A US geographic disposition independently associated with MACE (hazard ratio 1.53, 95% confidence interval 1.22 to 1.92, p <0.001). In conclusion, in participants with stable coronary disease, coronary atheroma progression rates are modestly higher in US-based compared to non-US-based participants. Elective coronary revascularization rates however are disproportionately greater in US-based participants.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Puri R, Nicholls SJ, St John J, Tuzcu EM, ... Wolski K, Nissen SE
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666179
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Abstract

Usefulness of Transesophageal Echocardiography to Confirm Clinical Utility of CHA(2)DS(2)-VASc and CHADS(2) Scores in Atrial Flutter.

Parikh MG, Aziz Z, Krishnan K, Madias C, Trohman RG
The CHA(2)DS(2)-VASc and CHADS(2) risk stratification schemes are used to predict thromboembolism and ischemic stroke in patients with atrial fibrillation. However, limited data are available regarding the utility of these risk stratification schemes for stroke in patients with atrial flutter. A retrospective analysis of 455 transesophageal echocardiographic studies in patients with atrial flutter was performed to identify left atrial (LA) thrombi and/or spontaneous echocardiographic contrast (SEC). The CHA(2)DS(2)-VASc (Congestive heart failure, Hypertension, Age ≥75 years [doubled risk weight], Diabetes mellitus, previous Stroke/transient ischemic attack [doubled risk weight], Vascular disease, Age 65 to 74 years, Sex) and CHADS(2) (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack [double risk weight]) scores were calculated to stratify the risk of stroke or transient cerebrovascular ischemic events. Transesophageal echocardiography revealed LA thrombi in 5.3% and SEC in 25.9% of patients. Using CHADS(2), LA thrombus was found in 2.2% of the low-intermediate-risk group and 8.3% of the high-risk group (p = 0.005). SEC was found in 19.8% of the low-intermediate-risk group and 32% of the high-risk group (p = 0.004). Using CHA(2)DS(2)-VASc, LA thrombus was found in 1.7% of the low-intermediate-risk group and 6.5% of the high-risk group (p = 0.053). SEC was found in 11.8% of the low-intermediate-risk group versus 30.9% of the high-risk group (p = 0.004). The sensitivity for LA thrombus/SEC with a high CHADS(2) and CHA(2)DS(2)-VASc score was 64.8% and 88.7%, respectively (p = 0.0001). The specificity for LA thrombus/SEC with high CHADS(2) and CHA(2)DS(2)-VASc scores was 52.6% and 28.9%, respectively (p = 0.0001). In conclusion, both CHA(2)DS(2)-VASc and CHADS(2) scores are useful for stroke risk stratification in patients with atrial flutter. CHA(2)DS(2)-VASc had greater sensitivity for LA thrombus and SEC detection at the cost of reduced specificity.

Am J Cardiol: 02 Dec 2011; epub ahead of print
Parikh MG, Aziz Z, Krishnan K, Madias C, Trohman RG
Am J Cardiol: 02 Dec 2011; epub ahead of print | PMID: 22133753
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Impact:
Abstract

Frequency of Increase in Cardiac Troponin Levels After Peripheral Arterial Operations (Carotid Endarterectomy, Abdominal Aorta Procedure, Distal Bypass) and Their Effect on Medical Management.

Sandoval Y, Zakharova M, Rector TS, Brilakis ES, ... McFalls EO, Garcia S
The utility of measuring cardiac troponins (cTn) in asymptomatic patients during the perioperative period has been controversial. In the present substudy of the Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery Trial (NCT01558596), we hypothesized that surveillance of myocardial injury with cTnI in the perioperative period would lead to initiation or intensification of medical therapies for coronary artery disease. Increases in cTnI ≥0.01 μg/l in the perioperative period were considered clinically significant. Intensification of medical therapy was defined as initiation of aspirin or initiation or increases in the dose of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers, statins, or β blockers and was left to the discretion of treating physicians. From June 2011 to April 2015, a total of 185 patients (mean age 68 ± 7 years, 100% men) were enrolled in the trial. A total of 28 patients (15%) had significant increases in cTnI after vascular surgery, and 38 (20.5%) had their medical therapies intensified in the perioperative period. Among patients with increases in cTnI, 11 (39%) had intensification of medical therapy versus 27 patients (17%) with no or smaller increases in cTnI (p = 0.02). Among those patients with ΔcTnI ≥0.01 μg/l, hospital readmissions at 3 to 6 months were 7.6% for the intensification group versus 25% for the no intensification group (p = 0.18). Mortality rate at 6 months was low in both groups (2.6% vs 0%, respectively, p = 0.13). In conclusion, among patients undergoing vascular surgery, perioperative increases in cTn were associated with initiation or intensification of medical therapies for coronary artery disease at the time of discharge.

Am J Cardiol: 10 Oct 2016; epub ahead of print
Sandoval Y, Zakharova M, Rector TS, Brilakis ES, ... McFalls EO, Garcia S
Am J Cardiol: 10 Oct 2016; epub ahead of print | PMID: 27726853
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Abstract

Fetal Diagnosis of Interrupted Aortic Arch.

Vogel M, Vernon MM, McElhinney DB, Brown DW, Colan SD, Tworetzky W
To determine the frequency of prenatal detection among liveborn patients with an interrupted aortic arch (IAA), the accuracy of prenatal diagnosis, and the anatomic features associated with IAA in the fetus. The prenatal diagnosis of an IAA is challenging. The data on the features and outcomes of fetal IAA are limited. This was a retrospective review of the fetuses and neonates diagnosed with IAA at the Children\'s Hospital Boston. From 1988 to 2009, 26 fetuses were diagnosed with an IAA. Of these, 21 were live born, and 5 pregnancies were terminated. Of these 21 patients, 18 were confirmed to have an IAA after birth and 3 had severe aortic coarctation. Of the 56 patients diagnosed with an IAA as neonates, 3 had a prenatal echocardiogram that did not include the correct diagnosis. Among the liveborn patients with a postnatally confirmed IAA, 24% were diagnosed prenatally, which increased from 11% during the first 7-year period to 43% more recently. Also, 15% of the prenatally diagnosed patients with IAA had a family history of structural or genetic anomalies. In fetuses with an IAA, echocardiographic Z-scores for the aortic valve and ascending aorta were significantly lower than in normal fetuses, but the left ventricular dimensions were normal. Aortopulmonary diameter ratios were abnormally low. In conclusion, although the identification of IAA on a prenatal echocardiogram can be challenging, a number of anatomic features can facilitate the diagnosis. In particular, a low aortopulmonary diameter ratio in the absence of a ventricular size discrepancy should prompt consideration of this diagnosis. Despite the diagnostic challenges, the frequency of prenatal diagnosis of the IAA is increasing.

Am J Cardiol: 26 Feb 2010; 105:727-734
Vogel M, Vernon MM, McElhinney DB, Brown DW, Colan SD, Tworetzky W
Am J Cardiol: 26 Feb 2010; 105:727-734 | PMID: 20185024
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Abstract

Behavior of Unrepaired Perimembranous Ventricular Septal Defect in Young Adults.

Soufflet V, Van de Bruaene A, Troost E, Gewillig M, ... Post MC, Budts W
The number of adolescents and young adults with congenital heart defects, including ventricular septal defect (VSD), increases continuously. We evaluated the mid-term outcome of small and unclosed perimembranous VSDs (pmVSDs). All patients with a known unrepaired pmVSD at 16 years of age were selected from our database. The clinical, electrocardiographic, and echocardiographic changes between baseline and the latest follow-up examination were compared. A total of 220 patients (119 males, median age 18 years, interquartile range 7) could be included. During a median follow-up of 6 years (interquartile range 4, range 38), 2 patients died (1%; 1 from sudden death and 1 from end-stage heart failure). Endocarditis occurred in 8 patients (4%). One patient required pacemaker implantation (0.5%) and one required implantable cardioverter-defibrillator implantation (1%). Fifteen patients (7%) required a closing procedure. In 8 patients (4%), the pmVSD closed spontaneously. In the remaining 203 patients (93%), the QRS morphology changed in 5% and 1% lost sinus rhythm (p = 0.0001 and p = 0.015, respectively). The left ventricular ejection fraction and stroke volume index increased from 62 +/- 7% to 67 +/- 8% and from 41 +/- 11 to 44 +/- 15 ml/m(2) (p = 0.0001 and p = 0.035, respectively), the end-systolic diameter decreased, and the end-diastolic diameter did not change. Finally, patients with an open pmVSD developed more pulmonary arterial hypertension during follow-up (from 3% to 9%, p = 0.002). In conclusion, mid-term follow-up of adolescents and young adults with a small and unrepaired pmVSD was not uneventful. Some patients required intervention, but in others, spontaneous closure occurred. Electrocardiographic and structural changes were noticed, for which the clinical significance needs to be determined.

Am J Cardiol: 27 Jan 2010; 105:404-407
Soufflet V, Van de Bruaene A, Troost E, Gewillig M, ... Post MC, Budts W
Am J Cardiol: 27 Jan 2010; 105:404-407 | PMID: 20102957
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Abstract

Safety of Alirocumab (A PCSK9 Monoclonal Antibody) from 14 Randomized Trials.

Jones PH, Bays HE, Chaudhari U, Pordy R, ... Miller K, Robinson JG
Previous individual trials of alirocumab (a PCSK9 monoclonal antibody) showed significant low-density lipoprotein cholesterol reductions with overall treatment-emergent adverse event (TEAE) rates comparable with controls. This analysis evaluated safety data from 14 trials (4 phase 2 and 10 phase 3, 8 to 104 weeks; n = 5,234), in 2 pools according to control (placebo/ezetimibe). Overall, 3,340 patients received alirocumab (4,029 patient-years\' exposure), 1,276 received placebo, and 618 received ezetimibe. Incidence of deaths, serious TEAEs, discontinuations because of TEAEs, and overall TEAEs were similar between alirocumab and control groups. Alirocumab was associated with a higher incidence of local injection site reactions (7.4% vs 5.3% with placebo; 3.1% vs 2.3% with ezetimibe), pruritus (1.3% vs 0.4% placebo; 0.9% vs 0.5% ezetimibe), and upper respiratory tract infection signs and symptoms (2.1% vs 1.1% placebo; 1.3% vs 0.8% ezetimibe). Incidence of musculoskeletal, neurologic, neurocognitive, ophthalmologic, hepatic events, and TEAEs related to diabetes/diabetes complications was similar between alirocumab and control groups. In a prespecified analysis of phase 3 studies, adjudicated major adverse cardiovascular events (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, and unstable angina requiring hospitalization) occurred in 1.8% alirocumab versus 2.6% placebo patients (hazard ratio 0.69, 95% confidence interval 0.43 to 1.11) and 2.8% alirocumab versus 1.5% ezetimibe patients (hazard ratio 1.4, 95% confidence interval 0.65 to 3.02). In conclusion, pooled safety data from 14 trials demonstrate that alirocumab is generally well tolerated with a favorable safety profile.

Am J Cardiol: 11 Oct 2016; epub ahead of print
Jones PH, Bays HE, Chaudhari U, Pordy R, ... Miller K, Robinson JG
Am J Cardiol: 11 Oct 2016; epub ahead of print | PMID: 27729106
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Abstract

Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.

Lee SA, Yoon YE, Kim JE, Park JJ, ... Choi DJ, Choi SI
The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.

Am J Cardiol: 14 Oct 2016; epub ahead of print
Lee SA, Yoon YE, Kim JE, Park JJ, ... Choi DJ, Choi SI
Am J Cardiol: 14 Oct 2016; epub ahead of print | PMID: 27742424
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Abstract

Etiology of Heart Failure and Outcomes in Patients Hospitalized for Acute Decompensated Heart Failure With Preserved or Reduced Ejection Fraction.

Kajimoto K, Minami Y, Sato N, Kasanuki H, Investigators of the Acute Decompensated Heart Failure Syndromes (ATTEND) Registry
In the setting of acute decompensated heart failure (HF), relations among the etiology of HF, left ventricular systolic function, and outcomes are unclear. The aim of this study was to investigate the association of HF etiology with outcomes in patients with acute decompensated HF with a preserved or reduced ejection fraction (EF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry, 3,810 patients (1,601 with a preserved EF and 2,209 with a reduced EF) who had a hypertensive, ischemic, valvular, or idiopathic dilated etiology of HF were investigated to assess the association of etiology with a composite end point (all-cause mortality and readmission for HF). The median follow-up period after admission was 502 (381 to 759) days. The composite end point was reached in 44.6% and 41.7% of the preserved and reduced EF groups, respectively. After adjustment for multiple co-morbidities, the risk of the composite end point was comparable among hypertensive, ischemic, and valvular etiologies in the preserved EF group. In contrast, in the reduced EF group, ischemic etiology was associated with a tendency toward greater risk of the composite end point than hypertensive etiology (but this difference was not significant), whereas valvular etiology was associated with a significantly greater risk of the composite end point relative to hypertensive or idiopathic dilated etiology. In conclusion, this study demonstrated that taking the etiology of HF into account may help to reduce the heterogeneity of acute decompensated HF and assist in identifying patients at risk of adverse outcomes, especially among patients with reduced EF.

Am J Cardiol: 09 Oct 2016; epub ahead of print
Kajimoto K, Minami Y, Sato N, Kasanuki H, Investigators of the Acute Decompensated Heart Failure Syndromes (ATTEND) Registry
Am J Cardiol: 09 Oct 2016; epub ahead of print | PMID: 27720439
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Abstract

Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat With Incident Atrial Fibrillation (from the Framingham Heart Study).

Lee JJ, Yin X, Hoffmann U, Fox CS, Benjamin EJ
Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third-Generation Cohorts who participated in the multidetector computed tomography substudy examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and gender-adjusted incident AF rate per 1,000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and gender-adjusted model, greater pericardial fat (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03 to 1.34) and intrathoracic fat (HR 1.24, 95% CI 1.06 to 1.45) were associated with an increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99 to 1.30) for pericardial fat, 1.19 (1.01 to 1.40) for intrathoracic fat, and 1.09 (0.93 to 1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of body mass index, none of the associations remained significant (all p >0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Lee JJ, Yin X, Hoffmann U, Fox CS, Benjamin EJ
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666172
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Abstract

Contemporary Features, Risk Factors, and Prognosis of the Post-Pericardiotomy Syndrome.

Imazio M, Brucato A, Rovere ME, Gandino A, ... Spodick D, Adler Y
Contemporary series of postpericardiotomy syndrome (PPS) are lacking. The aim of this study was to evaluate the incidence, time course, features at presentation, risk factors, and prognosis of PPS. The study population consisted of 360 consecutive candidates to cardiac surgery enrolled in a prospective cohort study. PPS was diagnosed in 54 patients (15.0%; mean age 66 ± 12 years, 48.1% women): 79.6% in the first month, 13.0% in the second month, and 7.4% in the third month. Specific symptoms, signs, or features were pleuritic chest pain (55.6%), fever (53.7%), elevated markers of inflammation (74.1%), pericardial effusion (88.9%), and pleural effusion (92.6%). Cardiac tamponade was rare at presentation (1.9%). Female gender (hazard ratio 2.32, 95% confidence interval 1.22 to 4.39, p = 0.010), and pleura incision (hazard ratio 4.31, 95% confidence interval 2.22 to 8.33, p <0.001) were identified as risk factors in multivariate analysis. Patients with PPS had longer cardiac surgery stays (11.5 ± 4.6 vs 9.9 ± 4.7 days, p = 0.021) and rehabilitation stays (16.4 ± 6.7 vs 12.4 ± 6.2 days, p <0.001) and more readmissions (13.0% vs 0%, p <0.001). Adverse events after a mean follow-up period of 19.8 months were recurrences (3.7%), cardiac tamponade (<2%), but no cases of constriction. In conclusion, despite advances in cardiac surgery techniques, PPS is a common postoperative complication, generally occurring in the first 3 months after surgery. Severe complications are rare, but the syndrome is responsible for hospital stay prolongation and readmissions. Female gender and pleura incision are risk factors for PPS.

Am J Cardiol: 29 Jul 2011; epub ahead of print
Imazio M, Brucato A, Rovere ME, Gandino A, ... Spodick D, Adler Y
Am J Cardiol: 29 Jul 2011; epub ahead of print | PMID: 21798503
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Abstract

Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.

den Boer SL, Rizopoulos D, du Marchie Sarvaas GJ, Backx AP, ... Helbing WA, Dalinghaus M
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.

Am J Cardiol: 02 Oct 2016; epub ahead of print
den Boer SL, Rizopoulos D, du Marchie Sarvaas GJ, Backx AP, ... Helbing WA, Dalinghaus M
Am J Cardiol: 02 Oct 2016; epub ahead of print | PMID: 27692597
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Abstract

Meta-Analysis of Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes and All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus.

Tang H, Fang Z, Wang T, Cui W, Zhai S, Song Y
The benefit or risk of sodium glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus has not been established. We aimed to assess the comparative CV safety and mortality risk associated with the use of SGLT2 inhibitors. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were systematically searched up to January 27, 2016, to identify randomized controlled trials (RCTs) with the use of SGLT2 inhibitors of at least 24 weeks of duration. The primary outcomes included all-cause mortality and major adverse cardiovascular events. A random-effects network meta-analysis was performed to calculate the odds ratio (OR) with 95% CI. We identified 37 eligible trials involving 29,859 patients that compared 3 SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to placebo and other active antidiabetic treatments. Of all direct and indirect comparisons, only empagliflozin compared with placebo was significantly associated with lower risk of all-cause mortality (OR 0.67, 95% CI 0.56 to 0.81) and major adverse cardiovascular events (OR 0.81, 95% CI 0.70 to 0.93). However, the significant effect of empagliflozin was largely driven by one large randomized trial (EMPA-REG OUTCOME trial). Neither dapagliflozin nor canagliflozin was significantly associated with any harm. In conclusion, current RCT evidence suggests that 3 common SGLT2 inhibitors are not associated with increased risk of all-cause mortality and CV outcomes when used to treat patients with type 2 diabetes mellitus. Although empagliflozin may have a protective effect, further confirmative data from rigorous RCTs are needed.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Tang H, Fang Z, Wang T, Cui W, Zhai S, Song Y
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666177
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Abstract

Frequency of and Prognostic Significance of Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valve Implantation.

Sannino A, Stoler RC, Lima B, Szerlip M, ... Mack MJ, Grayburn PA
The prognostic implications of preexisting atrial fibrillation (AF) and new-onset AF (NOAF) in transcatheter aortic valve implantation (TAVI) remain uncertain. This study assesses the epidemiology of AF in patients treated with TAVI and evaluates their outcomes according to the presence of preexisting AF or NOAF. A retrospective analysis of 708 patients undergoing TAVI from 2 heart hospitals was performed. Patients were divided into 3 study groups: sinus rhythm (n = 423), preexisting AF (n = 219), and NOAF (n = 66). Primary outcomes of interest were all-cause death and stroke both at 30-day and at 1-year follow-up. Preexisting AF was present in 30.9% of our study population, whereas NOAF was observed in 9.3% of patients after TAVI. AF and NOAF patients showed a higher rate of 1-year all-cause mortality compared with patients in sinus rhythm (14.6% vs 6.5% for preexisting AF and 16.3% vs 6.5% for NOAF, p = 0.007). No differences in 30-day mortality were observed between groups. In patients with AF (either preexisting and new-onset), those discharged with single antiplatelet therapy displayed higher mortality rates at 1 year (42.9% vs 11.7%, p = 0.006). Preexisting AF remained an independent predictor of mortality at 1-year follow-up (hazard ratio [HR] 2.34, 95% CI 1.22 to 4.48, p = 0.010). Independent predictors of NOAF were transapical and transaortic approach as well as balloon postdilatation (HR 3.48, 95% CI 1.66 to 7.29, p = 0.001; HR 5.08, 95% CI 2.08 to 12.39, p <0.001; HR 2.76, 95% CI 1.25 to 6.08, p = 0.012, respectively). In conclusion, preexisting AF is common in patients undergoing TAVI and is associated with a twofold increased risk of 1-year mortality. This negative effect is most pronounced in patients discharged with single antiplatelet therapy compared with other antithrombotic regimens.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Sannino A, Stoler RC, Lima B, Szerlip M, ... Mack MJ, Grayburn PA
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666171
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Abstract

Relation Among Clot Burden, Right-Sided Heart Strain, and Adverse Events After Acute Pulmonary Embolism.

Hariharan P, Dudzinski DM, Rosovsky R, Haddad F, ... Chang Y, Kabrhel C
Computed tomography pulmonary angiogram (CTPA) provides a volumetric assessment of clot burden in acute pulmonary embolism (PE). However, it is unclear if clot burden is associated with right-sided heart strain (RHS) or adverse clinical events (ACE). We prospectively enrolled Emergency Department patients with PE (in CTPA) from 2008 to 2011. We assigned 1 to 9 points as clot burden score, based on whether emboli were saddle, central, lobar, segmental, and subsegmental. We evaluated a novel score (the "CT-PASS") based on the sum (in millimeters) of the largest filling defects in the right and left pulmonary vasculature. Our primary outcome was RHS, defined by imaging (echocardiography or CTPA) or cardiac biomarkers. Our secondary outcomes included 5-day ACE. We included 271 patients (50% women), with a mean age of 59 ± 17 years. Based on CTPA, 131 patients (48%) had central PE (clot burden score ≥5 points). The median CT-PASS was 9.1 mm (interquartile range 4.9 to 16.4). In univariate analysis, higher clot burden (highest quartile CT-PASS) was associated with RHS (p = 0.003). In multivariate analysis, after adjusting for RHS, age, and gender, central PE (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.10 to 7.81) and CT-PASS >20 mm (OR 3.54, 95% CI 1.39 to 8.97) were significantly associated with ACE. However, this association of central PE with ACE was not statistically significant after excluding patients with shock index >1 (OR 2.56, 95% CI 0.62 to 10.64). In conclusion, highest quartile CT-PASS was associated with RHS and central PE and ACE, but this association was not statistically significant in hemodynamically stable PE.

Am J Cardiol: 14 Oct 2016; epub ahead of print
Hariharan P, Dudzinski DM, Rosovsky R, Haddad F, ... Chang Y, Kabrhel C
Am J Cardiol: 14 Oct 2016; epub ahead of print | PMID: 27742425
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Abstract

Nomograms for Aortic Root Diameters in Children Using Two-Dimensional Echocardiography.

Gautier M, Detaint D, Fermanian C, Aegerter P, ... Vahanian A, Jondeau G
The evaluation of aortic root dilation is of major importance for the diagnosis and follow-up of patients with diverse diseases, including the Marfan syndrome. However, we noted that the available nomograms suggested a lower aortic root dilation rate in adults (75%) than in children (90%), when the opposite would have been expected. To establish new nomograms, we selected a population of 353 normal children. We took transthoracic echocardiographic measurements of the aortic root diameters at the level of the aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta according to the American Society of Echocardiography recommendations. All diameters correlated well with the height, weight, body surface area, and age (r = 0.75 to 0.84, p <0.0001). Covariance analysis adjusting for body surface area showed slightly larger diameters at the level of the sinuses of Valsalva in male children than in female children (+1 mm, p = 0.0002). Equations and derived nomograms were developed, giving the upper limit of normal (allowing simple recognition of aortic dilation) and the Z score (allowing fine quantification of dilation and differentiation of normal growth from pathologic dilation) for all 4 aortic root diameters (ie, aortic annulus, sinuses of Valsalva, sinotubular junction, and proximal ascending aorta) according to body surface area and gender. We applied the nomograms to 282 children with confirmed Marfan syndrome, of whom 65.2% presented with dilation of the sinuses of Valsalva. In conclusion, we propose equations to calculate the upper limit of normal and Z-score for aortic root diameters measured by 2-dimensional echocardiography, which should be useful tools for the diagnosis and follow-up of aortic root aneurysms in children.

Am J Cardiol: 09 Mar 2010; 105:888-894
Gautier M, Detaint D, Fermanian C, Aegerter P, ... Vahanian A, Jondeau G
Am J Cardiol: 09 Mar 2010; 105:888-894 | PMID: 20211339
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Abstract

Impact of Lipoprotein(a) on Long-term Outcomes in Patients With Diabetes Mellitus Who Underwent Percutaneous Coronary Intervention.

Konishi H, Miyauchi K, Shitara J, Endo H, ... Suwa S, Daida H
Patients with diabetes mellitus (DM) are at twofold to fourfold higher cardiovascular risk than those without DM. Serum levels of lipoprotein(a) (Lp(a)) can be risk factors for adverse events. However, the clinical implications of Lp(a) in patients with DM who underwent percutaneous coronary intervention (PCI) is unknown. The aim of the study was to determine the role of Lp(a) in patients with DM who underwent PCI. A total of 3,508 patients were treated by PCI from 1997 to 2011 at our institution. Among them, we analyzed consecutive 1,546 patients with DM. Eligible 1,136 patients were divided into 2 groups (high Lp(a) [n = 575] and low Lp(a) [n = 561]) by the median of Lp(a) levels. The number of chronic kidney disease, multivessel disease, and the level of LDL-C were higher in the group with high Lp(a) than with low Lp(a). The median follow-up period was 4.7 years. Event rate of all-cause death was same between the 2 groups (p = 0.37). However, cumulative incidence of cardiac death and acute coronary syndrome was significantly higher in the high Lp(a) than in the low Lp(a) group (p = 0.03). Multivariable analysis selected a high Lp(a) level as an independent predictor of cardiac death and acute coronary syndrome (hazard ratio 1.20; 95% confidence interval 1.00 to 1.42; p = 0.04). In conclusion, a high Lp(a) value could be associated with advanced cardiac events after PCI for patients with DM.

Am J Cardiol: 06 Oct 2016; epub ahead of print
Konishi H, Miyauchi K, Shitara J, Endo H, ... Suwa S, Daida H
Am J Cardiol: 06 Oct 2016; epub ahead of print | PMID: 27712648
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Abstract

Impact of Gender on the Prognostic Value of Coronary Artery Calcium in Symptomatic Patients With Normal Single-Photon Emission Computed Tomography Myocardial Perfusion.

Engbers EM, Timmer JR, Ottervanger JP, Mouden M, Knollema S, Jager PL
The coronary artery calcium (CAC) score provides independent prognostic value on top of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). We sought to determine whether the prognostic value of the CAC score in patients with normal SPECT MPI is gender specific. We studied 3,705 consecutive symptomatic patients without a history of coronary artery disease with normal SPECT MPI. All patients underwent concomitant CAC scoring, which was categorized as CAC score 0, 1 to 99, 100 to 399, 400 to 999, or ≥1,000. Major adverse cardiac events were defined as revascularization, nonfatal myocardial infarction, or all-cause mortality. The median CAC score was 9 in women (interquartile range 0 to 113) and 47 in men (interquartile range 1 to 307, p <0.001). The annual event rate was lower in women than in men (1.6% and 2.7%, respectively, p <0.001). When stratified by CAC score, annual event rates were similar (for women and men, respectively: CAC score 0, 0.6% and 0.5%, p = 0.95; CAC score 1 to 99, 0.9% and 1.2%, p = 0.45; CAC score 100 to 399, 2.7% and 3.8%, p = 0.23; CAC score 400 to 999, 3.8% and 5.3%, p = 0.34; CAC score ≥1,000, 8.4% and 8.7%, p = 0.99). The CAC score was an independent predictor of major adverse cardiac events in both genders (CAC score ≥1,000: hazard ratio for women 8.5, 95% confidence interval 4.0 to 18.1; hazard ratio for men 14.8, 95% confidence interval 5.3 to 41.1). In conclusion, risk for events is similar for both genders when stratified by CAC score, wherein a high CAC score carries a high risk for events despite normal SPECT MPI. Our findings do not reveal a gender-specific prognostic value of the CAC score.

Am J Cardiol: 07 Oct 2016; epub ahead of print
Engbers EM, Timmer JR, Ottervanger JP, Mouden M, Knollema S, Jager PL
Am J Cardiol: 07 Oct 2016; epub ahead of print | PMID: 27717443
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Abstract

Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study).

Ko D, Riles EM, Marcos EG, Magnani JW, ... Yin X, Rienstra M
Previous studies have shown several metabolic biomarkers to be associated with prevalent and incident atrial fibrillation (AF), but the results have not been replicated. We investigated metabolite profiles of 2,458 European ancestry participants from the Framingham Heart Study without AF at the index examination and followed them for 10 years for new-onset AF. Amino acids, organic acids, lipids, and other plasma metabolites were profiled by liquid chromatography-tandem mass spectrometry using fasting plasma samples. We conducted Cox proportional hazard analyses for association between metabolites and new-onset AF. We performed hypothesis-generating analysis to identify novel metabolites and hypothesis-testing analysis to confirm the previously reported associations between metabolites and AF. Mean age was 55.1 ± 9.9 years, and 53% were women. Incident AF developed in 156 participants (6.3%) in 10 years of follow-up. A total of 217 metabolites were examined, consisting of 54 positively charged metabolites, 59 negatively charged metabolites, and 104 lipids. None of the 217 metabolites met our a priori specified Bonferroni corrected level of significance in the multivariate analyses. We were unable to replicate previous results demonstrating associations between metabolites that we had measured and AF. In conclusion, in our metabolomics approach, none of the metabolites we tested were significantly associated with the risk of future AF.

Am J Cardiol: 25 Sep 2016; epub ahead of print
Ko D, Riles EM, Marcos EG, Magnani JW, ... Yin X, Rienstra M
Am J Cardiol: 25 Sep 2016; epub ahead of print | PMID: 27666170
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Abstract

Factors Associated With Resource Utilization and Coronary Artery Dilation in Refractory Kawasaki Disease (from the Pediatric Health Information System Database).

Lo JY, Minich LL, Tani LY, Wilkes J, Ding Q, Menon SC
Management guidelines for refractory Kawasaki disease (KD) are vague. We sought to assess practice variation and identify factors associated with large/complex coronary artery aneurysms (LCAA) and resource utilization in refractory KD. This retrospective cohort study identified patients aged ≤18 years with KD (2004 to 2014) using the Pediatric Health Information System. Refractory KD was defined as receiving >1 dose of intravenous immunoglobulin. Demographics, medications, concomitant infections, length of stay (LOS), and charges were collected. Antithrombotic therapy was a surrogate for LCAA. LOS and hospital charges assessed resource utilization. Multivariate regression identified factors associated with LOS, charges, and LCAA. Of 14,194 patients with KD, 2,974 (21%) had refractory KD and 203 of those 2,974 (7%) had LCAA. Additional intravenous immunoglobulin was the sole medication in 77%. Other medications added were steroids (18%), infliximab (2%), and both (3%). Warfarin, low-molecular-weight heparin, tissue plasminogen activator, and clopidogrel were prescribed with equal frequency (2%). Male gender (adjusted relative risk 1.52, 95% confidence interval [CI] 1.08 to 2.16, p <0.01), admission to an intensive care unit (4.79, 95% CI 3.40 to 6.74, p <0.001), arrhythmia (3.00, 95% CI 1.94 to 4.65, p <0.001), and concomitant viral infection (2.29, 95% CI 1.49 to 3.52, p <0.001) were associated with LCAA. Severe illness, race, region, and payer were independently associated with increased charges (p <0.05 for all). In conclusion, treatment for refractory KD varies widely. Concomitant viral infection was associated with a greater risk of LCAA in refractory KD. Better understanding of optimal management may improve outcomes and decrease both variability in management and resource utilization for refractory KD.

Am J Cardiol: 24 Sep 2016; epub ahead of print
Lo JY, Minich LL, Tani LY, Wilkes J, Ding Q, Menon SC
Am J Cardiol: 24 Sep 2016; epub ahead of print | PMID: 27665207
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Abstract

Comparison of Outcomes of Transcatheter Aortic Valve Replacement Plus Percutaneous Coronary Intervention Versus Transcatheter Aortic Valve Replacement Alone in the United States.

Singh V, Rodriguez AP, Thakkar B, Patel NJ, ... Elmariah S, O\'Neill WW
Transcatheter aortic valve replacement (TAVR) with percutaneous coronary intervention (PCI) has emerged as a less-invasive therapeutic option for high surgical risk patients with aortic stenosis and coronary artery disease. The aim of this study was to determine the outcomes of TAVR when performed with PCI during the same hospitalization. We identified patients using the International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes from the Nationwide Inpatient Sample between the years 2011 and 2013. A total of 22,344 TAVRs were performed between 2011 and 2013. Of these, 21,736 (97.3%) were performed without PCI (TAVR group) while 608 (2.7%) along with PCI (TAVR + PCI group). Among the TAVR + PCI group, 69.7% of the patients had single-vessel, 22.2% had 2-vessel, and 1.6% had 3-vessel PCI. Drug-eluting stents were more commonly used than bare-metal stents (72% vs 28%). TAVR + PCI group witnessed significantly higher rates of mortality (10.7% vs 4.6%) and complications: vascular injury requiring surgery (8.2% vs 4.2%), cardiac (25.4% vs 18.6%), respiratory (24.6% vs 16.1%), and infectious (10.7% vs 3.3%), p <0.001% for all, compared with the TAVR group. The mean length of hospital stay and cost of hospitalization were also significantly higher in the TAVR + PCI group. The propensity score-matched analysis yielded similar results. In conclusion, performing PCI along with TAVR during the same hospital admission is associated with higher mortality, complications, and cost compared with TAVR alone. Patients would perhaps be better served by staged PCI before TAVR.

Am J Cardiol: 24 Sep 2016; epub ahead of print
Singh V, Rodriguez AP, Thakkar B, Patel NJ, ... Elmariah S, O'Neill WW
Am J Cardiol: 24 Sep 2016; epub ahead of print | PMID: 27665205
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Abstract

Effect of Heart Failure With Preserved Ejection Fraction on Nitric Oxide Metabolites.

Zamani P, French B, Brandimarto JA, Doulias PT, ... Ischiropoulos H, Cappola TP
Endothelial function may be deranged in heart failure with preserved ejection fraction (HFpEF). Serum NO-derived metabolites (NOm) might provide a biochemical surrogate of endothelial function in patients with heart failure (HF). We measured serum NOm in 415 participants in the Penn HF Study. Participants with HFpEF (n = 82) and those whose EF had recovered (Recovered-HF, n = 125) were matched 1:1 to heart failure with reduced ejection fraction (HFrEF) participants based on age, gender, race, tobacco use, and eGFR. Serum NOm levels were quantified after chemical reduction coupled with gas-phase chemiluminescence detection. After adjustment for matching covariates and BMI, HFpEF (34.5 μM; interquartile range [IQR] 25.0, 51.5) participants had lower NOm levels than HFrEF (41.0 μM; IQR 28.3, 58.0; ratio of HFpEF:HFrEF 0.82, 95% confidence interval [CI] 0.67 to 0.99; p = 0.04), which further decreased when adjusted for covariates that affect endothelial function (ratio 0.79, 95% CI 0.65 to 0.98; p = 0.03). There were no differences between HFrEF (34.0; IQR 25.3, 49.0) and matched Recovered-HF (36.0 μM; IQR 25.0, 55.0) or HFpEF and Recovered-HF. Age (+21%/10-year increase, p <0.001) and black race (-28%, p = 0.03) associated with NOm in HFpEF, whereas age (+11%/10-year increase, p = 0.03), current tobacco use (+67%, p = 0.01), and eGFR (p = 0.01) associated with NOm in Recovered-HF. In conclusion, HFpEF participants have reduced NOm compared with HFrEF in this matched cohort. This might suggest either compromised endothelial function or poor dietary intake. Black race was associated with lower NOm in HFpEF.

Am J Cardiol: 14 Oct 2016; epub ahead of print
Zamani P, French B, Brandimarto JA, Doulias PT, ... Ischiropoulos H, Cappola TP
Am J Cardiol: 14 Oct 2016; epub ahead of print | PMID: 27742422
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Abstract

Long-Term Follow-Up of Patients With Previous Coronary Artery Bypass Grafting Undergoing Percutaneous Coronary Intervention for Chronic Total Occlusion.

Toma A, Stähli BE, Gick M, Colmsee H, ... Neumann FJ, Buettner HJ
Successful revascularization of chronic total occlusions (CTOs) has been associated with clinical benefit. Data on outcomes in patients with previous coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI) for CTO, however, are scarce. A total of 2,002 consecutive patients undergoing PCI for CTO from January 2005 to December 2013 were divided into patients with and without previous CABG, and outcomes were retrospectively assessed. The primary outcome measure was all-cause mortality. Median follow-up was 2.6 years (interquartile range 1.1 to 3.1). A total of 292 patients (15%) had previous CABG; they were older and had a greater prevalence of comorbidities. Procedural success was achieved in 75% and 84% of patients in the previous CABG and the non-CABG groups (p <0.001), respectively. All-cause mortality was 16% and 11% in the previous CABG and the non-CABG groups (p = 0.002), and differences were mitigated after adjustment for baseline characteristics (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.86 to 1.74, p = 0.27). All-cause death was significantly reduced in patients with procedural success, both in the previous CABG (11% vs 32%, adjusted HR 0.43, 95% CI 0.24 to 0.77, p = 0.005) and the non-CABG groups (10% vs 20%, adjusted HR 0.63, 95% CI 0.45 to 0.86, p = 0.004), with similar mortality benefits associated with successful revascularization in both groups (interaction p = 0.24). In conclusion, the relative survival benefit of successful recanalization of CTO is independent of previous CABG. However, owing to a greater baseline risk, the absolute survival benefit of successful CTO procedures is more pronounced in patients with previous CABG than in non-CABG patients.

Am J Cardiol: 02 Oct 2016; epub ahead of print
Toma A, Stähli BE, Gick M, Colmsee H, ... Neumann FJ, Buettner HJ
Am J Cardiol: 02 Oct 2016; epub ahead of print | PMID: 27692593
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Abstract

Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT).

Lip GY, Waldo AL, Ip J, Martin DT, ... Halperin JL, IMPACT Investigators
Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.

Am J Cardiol: 24 Sep 2016; epub ahead of print
Lip GY, Waldo AL, Ip J, Martin DT, ... Halperin JL, IMPACT Investigators
Am J Cardiol: 24 Sep 2016; epub ahead of print | PMID: 27665206
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Abstract

Acute Myocarditis and ST-Segment Elevation.

Shahid M, Hoey E, Basavarajaiah S
We report a case of focal myocarditis in a young boy mimicking acute ST-segment elevation MI. He presented with chest pain and the EKG changes were consistent with infero-laeral ST-segment elevation MI. Coronary angiogram revealed smooth arteries with no obstruction. Troponin was significantly elevated and the echocardiogram exhibited mildly impaired LV function with hypokinetic inferior and lateral walls. Subsequently performed cardiac magnetic resonance imaging confirmed the diagnosis of myocarditis by exhibiting classic features of delayed gadolinium enhancement in the epi and mid-myocardial regions of the lateral wall sparing the sub-endocardial region. This case exhibits the use of cardiac magnetic resonance imaging for diagnosis in such scenarios as often if the angiogram is normal other differential diagnosis are often speculated without actual evidence.

Am J Cardiol: 14 Oct 2016; epub ahead of print
Shahid M, Hoey E, Basavarajaiah S
Am J Cardiol: 14 Oct 2016; epub ahead of print | PMID: 27742420
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Abstract

Clinical Evaluation Versus Undetectable High-Sensitivity Troponin for Assessment of Patients With Acute Chest Pain.

Sanchis J, García-Blas S, Carratalá A, Valero E, ... Bosch X, Núñez J
Decision-making in acute chest pain remains challenging despite normal (below ninety-ninth percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ninety-ninth percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised 682 patients (November 2010 to September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/l). The main end point was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina, or revascularization) at a 4-year median follow-up; secondary end point was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain) and 2 points (recurrent pain and prior ischemic heart disease). The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/l), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI(Thrombolysis In Myocardial Infarction) risk (0.68, 0.77) or GRACE(Global Registry of Acute Coronary Events) (0.50, 0.47) scores. Likewise, the negative predictive values of score = 0 (97.5%, 100%) and ≤1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both clinical scores of 0 and ≤1 better classified patients at risk of MACE (p = 0.0001, log-rank test) than hs-cTnT <5 ng/l (p = 0.06). In conclusion, clinical data can guide decision-making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs-cTnT.

Am J Cardiol: 24 Sep 2016; epub ahead of print
Sanchis J, García-Blas S, Carratalá A, Valero E, ... Bosch X, Núñez J
Am J Cardiol: 24 Sep 2016; epub ahead of print | PMID: 27665208
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Abstract

Effect of New-Onset Left Bundle Branch Block After Transcatheter Aortic Valve Implantation (CoreValve) on Mortality, Frequency of Re-Hospitalization, and Need for Pacemaker.

López-Aguilera J, Segura Saint-Gerons JM, Bellido FM, Suárez de Lezo Herreros de Tejada J, ... Pavlovic D, de Lezo Cruz Conde JS
New-onset conduction disturbances are common after transcatheter aortic valve implantation (TAVI). The most common complication is left bundle branch block (LBBB). The clinical impact of new-onset LBBB after TAVI remains controversial. The aim of this study was to analyze the clinical impact of new-onset LBBB in terms of mortality and morbidity (need for pacemakers and admissions for heart failure) at long-term follow-up. From April 2008 to December 2014, 220 patients who had severe aortic stenosis were treated with the implantation of a CoreValve prosthesis. Sixty-seven of these patients were excluded from the analysis, including 22 patients with pre-existing LBBB and 45 with a permanent pacemaker, implanted previously or within 72 hours of implantation. The remaining 153 patients were divided into 2 groups: group 1 (n = 80), those with persistent new-onset LBBB, and group 2 (n = 73), those without conduction disturbances after treatment. Both groups were followed up at 1 month, 6 months, 12 months, and yearly thereafter. Persistent new-onset LBBB occurred in 80 patients (36%) immediately after TAVI; 73 patients (33%) did not develop conduction disturbances. The mean follow-up time of both groups was 32 ± 22 months (range 3 to 82 months), and there were no differences in time between the groups. There were no differences in mortality between the groups (39% vs 48%, p = 0.58). No differences were observed between the groups in re-hospitalizations for heart failure (11% vs 16%, p = 0.55). Group 1 did not require pacemaker implantation more often at follow-up (10% vs 13%, p = 0.38) than group 2. In conclusion, new-onset LBBB was not associated with a higher incidence of late need for a permanent pacemaker after CoreValve implantation. In addition, it was not associated with a higher risk of late mortality or re-hospitalization.

Am J Cardiol: 19 Sep 2016; epub ahead of print
López-Aguilera J, Segura Saint-Gerons JM, Bellido FM, Suárez de Lezo Herreros de Tejada J, ... Pavlovic D, de Lezo Cruz Conde JS
Am J Cardiol: 19 Sep 2016; epub ahead of print | PMID: 27645763
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Abstract

Adiponectin and Risk of Coronary Heart Disease in Apparently Healthy Men and Women (from the EPIC-Norfolk Prospective Population Study).

Côté M, Cartier A, Reuwer AQ, Arsenault BJ, ... Boekholdt SM, Khaw KT
The objective of the present study was to evaluate the association between adiponectin levels and incidence of coronary heart disease (CHD). We performed a prospective case-control analysis nested in the EPIC-Norfolk cohort. Participants were apparently healthy men and women 45 to 79 years of age who developed fatal or nonfatal CHD during an average follow-up period of 7.7 ± 1.1 years. In total 1,035 participants with incident CHD were matched for age, gender, and enrollment time to 1,920 controls who remained free of CHD over the study follow-up. Baseline nonfasting plasma adiponectin concentrations were determined by enzyme-linked immunosorbent assay. Adiponectin levels were lower in participants with CHD than in matched controls (men 8.74 vs 9.13 μg/ml, p = 0.01; women 12.6 vs 13.4 μg/ml, p = 0.03). A 1-μg/ml increment in adiponectin was associated with decreased CHD risk (odds ratio 0.78, 95% confidence interval 0.63 to 0.96, p = 0.02, in men; odds ratio 0.73, 95% confidence interval 0.55 to 0.96, p = 0.03, in women). However, this association was no longer significant after adjustment for established cardiovascular risk factors. Stratification of participants according to metabolic syndrome status showed that men and women with metabolic syndrome had a higher CHD risk, irrespective of their adiponectin levels. In conclusion, although a low adiponectin concentration is associated with an increased CHD risk, findings of the present study do not suggest that its measurement is useful to refine CHD risk assessment once traditional risk factors and clinical features of the metabolic syndrome have been considered.

Am J Cardiol: 09 May 2011; epub ahead of print
Côté M, Cartier A, Reuwer AQ, Arsenault BJ, ... Boekholdt SM, Khaw KT
Am J Cardiol: 09 May 2011; epub ahead of print | PMID: 21550577
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Abstract

Depressive Symptoms, Cardiac Disease Severity, and Functional Status in Patients With Coronary Artery Disease (from the Heart and Soul Study).

Schopfer DW, Regan M, Heidenreich PA, Whooley MA
Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly influenced by depressive symptoms as it is by cardiovascular disease severity.

Am J Cardiol: 24 Sep 2016; epub ahead of print
Schopfer DW, Regan M, Heidenreich PA, Whooley MA
Am J Cardiol: 24 Sep 2016; epub ahead of print | PMID: 27665203
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Abstract

Prevalence of Dyssynchrony and Relation With Long-Term Outcome in Patients After Acute Myocardial Infarction.

Antoni ML, Boden H, Hoogslag GE, Ewe SH, ... Bax JJ, Delgado V
The impact of left ventricular (LV) dyssynchrony on the long-term outcomes of patients with acute myocardial infarction (AMI) remains unknown. The purpose of the present study was to evaluate the prevalence of LV dyssynchrony after AMI and the potential relation with adverse events. A total of 976 consecutive patients admitted with AMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was performed <48 hours after admission. LV dyssynchrony was assessed with speckle-tracking imaging and calculated as the time difference between the earliest and latest activated segments. Patients were followed up for the occurrence of all-cause mortality (the primary end point) or the composite secondary end point (heart failure hospitalization and all-cause mortality). Within 48 hours of admission for the index infarction, mean LV dyssynchrony was 61 ±79 ms, and 14% of the patients demonstrated a ≥130-ms time difference, defined as significant LV dyssynchrony. During a mean follow-up period of 40 ±17 months, 82 patients (8%) reached the primary end point. In addition, 36 patients (4%) were hospitalized for heart failure. The presence of LV dyssynchrony was associated with an increased risk for all-cause mortality and hospitalization for heart failure during long-term follow-up (adjusted hazard ratio 1.06, 95% confidence interval 1.05 to 1.08, p <0.001, per 10-ms increase). Moreover, LV dyssynchrony provided incremental value over known clinical and echocardiographic risk factors for the prediction of adverse outcomes. In conclusion, LV dyssynchrony is a strong predictor of long-term mortality and hospitalization for heart failure in a population of patients admitted with ST-segment elevation AMI treated with primary percutaneous coronary intervention.

Am J Cardiol: 12 Sep 2011; epub ahead of print
Antoni ML, Boden H, Hoogslag GE, Ewe SH, ... Bax JJ, Delgado V
Am J Cardiol: 12 Sep 2011; epub ahead of print | PMID: 21906706
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Abstract

Usefulness of Atrial Fibrillation as a Marker for Adverse Cardiovascular Outcomes in Both Primary and Secondary Prevention in Patients With Implantable Cardioverter-Defibrillators.

Chang IC, Agamawi YM, Austin E, Adkisson WO, ... Benditt DG, Chen LY
Whether the risk factors for cardiovascular (CV) outcomes are different in primary versus secondary prevention implantable cardioverter-defibrillator (ICD) patients is unclear. We sought to identify predictors of CV outcomes in ICD recipients for primary (G1) versus secondary prevention (G2). Consecutive patients who had ICD implanted during August 2005 to December 2009 were included. The primary outcome was a composite of appropriate shock, acute coronary syndrome, ischemic stroke, coronary revascularization, heart failure exacerbation, CV hospitalization, or all-cause death. We used Cox proportional hazards model and a stepwise selection method to fit the most parsimonious model to predict the primary outcome in all patients and separately for G1 and G2 patients. We followed 223 (184 G1 and 39 G2, mean age 61 years) patients through December 31, 2012; 141 (63.2%) developed the primary outcome. In all patients, atrial fibrillation (AF; hazard ratio 6.72, 95% CI 4.20 to 10.75; p <0.001), use of antiarrhythmic drug (1.55, 1.02 to 2.36; p = 0.04), and lower estimated glomerular filtration rate (0.99, 0.98 to 0.997; p = 0.01) were associated with increased risk of the primary outcome; the attributable risks were 21.6%, 16.0%, and 15.9%, respectively. In G1, AF, hypertension, and lower estimated glomerular filtration rate were associated with increased risk, whereas in G2, AF, use of antiarrhythmic drug, and nonischemic cardiomyopathy were associated with increased risk. In conclusion, although risk factors are different for primary and secondary prevention patients, AF is a strong and consistent risk factor for adverse outcomes in both populations.

Am J Cardiol: 20 Sep 2016; epub ahead of print
Chang IC, Agamawi YM, Austin E, Adkisson WO, ... Benditt DG, Chen LY
Am J Cardiol: 20 Sep 2016; epub ahead of print | PMID: 27649879
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Abstract

Usefulness of the Atrial Emptying Fraction to Predict Maintenance of Sinus Rhythm After Direct Current Cardioversion for Atrial Fibrillation.

Luong CL, Thompson DJ, Gin KG, Jue J, ... Colley P, Tsang TS
Atrial volumes indexed to body surface area (AVI) are robust predictors of nonvalvular atrial fibrillation (AF) recurrence after direct current cardioversion (DCCV). The incremental value of atrial emptying fraction (EmF) compared with atrial volumes as a predictor for recurrent AF after DCCV has not been evaluated. We sought to compare the predictive ability of baseline left atrial (LA) EmF, right atrial (RA) EmF, LAVI, and RAVI for post-DCCV AF recurrence at 6 months. The first 95 patients enrolled in the AF Clinic Registry with adequate echocardiogram imaging constituted the study cohort. Each patient underwent echocardiogram within 6 months before cardioversion. Maximal LAVI and RAVI, LA EmF, and RA EmF were performed offline using 4-chamber single-plane Simpson\'s method, averaged over 5 cycles. The mean age of the study cohort was 64 ± 12 years, and 67% were men. Only 28 patients (29%) who underwent DCCV remained in sinus rhythm at 6 months of follow-up. The remaining, 67 (71%) had reverted to AF or underwent ablation during the 6 months of follow-up. The overall performance for prediction of AF recurrence was greatest for RA EmF, area under the receiver operator characteristic curve (AUC): RA EmF 0.92, LA EmF 0.89, RAVI 0.76, and LAVI 0.63. RA and LA EmF AUCs were significantly higher than for LAVI or RAVI (max p = 0.02). In conclusion, although RAVI and LAVI are strong predictors of AF recurrence after DCCV, RA and LA EmF outperformed in this cohort.

Am J Cardiol: 22 Sep 2016; epub ahead of print
Luong CL, Thompson DJ, Gin KG, Jue J, ... Colley P, Tsang TS
Am J Cardiol: 22 Sep 2016; epub ahead of print | PMID: 27658922
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Abstract

Updates and Current Recommendations for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes: What It Means for Clinical Practice.

Cayla G, Silvain J, Collet JP, Montalescot G
The American Heart Association (AHA) and the American College of Cardiology (ACC) have recently updated their joint guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS, including unstable angina [UA] and non-ST-elevation myocardial infarction [NSTEMI]). These guidelines replace the 2007 guidelines and the focused updates from 2011 and 2012 and now combine UA and NSTEMI into a new classification, NSTE-ACS, and updating the terminology around noninvasive management to ischemia-guided strategy. The latest guidelines include updated recommendations for the use of the oral antiplatelet agents (P2Y12 inhibitors) prasugrel and ticagrelor as part of dual-antiplatelet therapy-the cornerstone of treatment for these patients. This report provides a comprehensive overview of the new and modified recommendations for the management of patients with NSTE-ACS and the evidence supporting them. Also, where appropriate, similarities and differences between the current recommendations of the AHA/ACC and those of the European Society of Cardiology (ESC) are highlighted. For example, the AHA/ACC recommends the P2Y12 inhibitor ticagrelor over clopidogrel in all patients with NSTE-ACS and clopidogrel, prasugrel, or ticagrelor for patients in whom percutaneous coronary intervention is planned, whereas the ESC guidelines specifically recommend individual P2Y12 inhibitors for particular patient subgroups.

Am J Cardiol: 01 Mar 2015; 115:10A-22A
Cayla G, Silvain J, Collet JP, Montalescot G
Am J Cardiol: 01 Mar 2015; 115:10A-22A | PMID: 25728969
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Abstract

Prevalence and Predictors of Early Discontinuation of Dual-Antiplatelet Therapy After Drug-Eluting Stent Implantation in Korean Population.

Cho MH, Shin DW, Yun JM, Shin JH, ... Kim EH, Kim HK
The administration of antiplatelet drugs for months after a drug-eluting stent implantation is critical in decreasing the risk of complications, and premature discontinuation of antiplatelet therapy before the recommended period is the most important predictor for late complications. Therefore, we investigated the prevalence and associated factors of premature discontinuation of antiplatelet therapy in patients in Korea. This retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort data. Patients who were treated with dual-antiplatelet therapy (DAPT) were identified with medication prescription data. The Kaplan-Meier failure time plot was used to illustrate the cumulative probability of treatment discontinuation. Cox regression analysis was conducted to compare predictors of early discontinuation of DAPT. The characteristics of the early discontinuation group were not significantly different from the guideline concordance group, except for a higher prevalence of disability and a lower rate of chronic kidney disease. In a Cox regression model, the presence of hypertension was identified as a negative predictor of early discontinuation, and disability was not a statistically significant predictor. The prevalence of early discontinuation was 31.0% and seems to be significantly higher than those reported from prospective studies, which may more accurately reflect the real-world situation. In conclusion, physicians should make more effort to educate patients on the risk associated with premature discontinuation of antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent, and further studies investigating the reasons for nonadherence of DAPT are needed to improve DAPT compliance.

Am J Cardiol: 19 Sep 2016; epub ahead of print
Cho MH, Shin DW, Yun JM, Shin JH, ... Kim EH, Kim HK
Am J Cardiol: 19 Sep 2016; epub ahead of print | PMID: 27645764
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Abstract

Five-Year Outcomes of Percutaneous Versus Surgical Coronary Revascularization in Patients With Diabetes Mellitus (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).

Marui A, Kimura T, Nishiwaki N, Mitsudo K, ... Sakata R, The CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators
We investigated the impact of diabetes mellitus on long-term outcomes of percutaneous coronary intervention (PCI) in the drug-eluting stent era versus coronary artery bypass grafting (CABG) in a real-world population with advanced coronary disease. We identified 3,982 patients with 3-vessel and/or left main disease of 15,939 patients with first coronary revascularization enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2 (patients without diabetes: n = 1,984 [PCI: n = 1,123 and CABG: n = 861], and patients with diabetes: n = 1,998 [PCI: n = 1,065 and CABG: n = 933]). Cumulative 5-year incidence of all-cause death after PCI was significantly higher than after CABG both in patients without and with diabetes (19.8% vs 16.2%, p = 0.01, and 22.9% vs 19.0%, p = 0.046, respectively). After adjusting confounders, the excess mortality risk of PCI relative to CABG was no longer significant (hazard ratio [HR] 1.16; 95% confidence interval [CI] 0.88 to 1.54; p = 0.29) in patients without diabetes, whereas it remained significant (HR 1.31; 95% CI 1.01 to 1.70; p = 0.04) in patients with diabetes. The excess adjusted risks of PCI relative to CABG for cardiac death, myocardial infarction (MI), and any coronary revascularization were significant in both patients without (HR 1.59, 95% CI 1.01 to 2.51, p = 0.047; HR 2.16, 95% CI 1.20 to 3.87, p = 0.01; and HR 3.30, 95% CI 2.55 to 4.25, p <0.001, respectively) and with diabetes (HR 1.45, 95% CI 1.00 to 2.51, p = 0.047; HR 2.31, 95% CI 1.31 to 4.08, p = 0.004; and HR 3.70, 95% CI 2.91 to 4.69, p <0.001, respectively). There was no interaction between diabetic status and the effect of PCI relative to CABG for all-cause death, cardiac death, MI, and any revascularization. In conclusion, in both patients without and with diabetes with 3-vessel and/or left main disease, CABG compared with PCI was associated with better 5-year outcomes in terms of cardiac death, MI, and any coronary revascularization. There was no difference in the direction and magnitude of treatment effect of CABG relative to PCI regardless of diabetic status.

Am J Cardiol: 02 Mar 2015; epub ahead of print
Marui A, Kimura T, Nishiwaki N, Mitsudo K, ... Sakata R, The CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators
Am J Cardiol: 02 Mar 2015; epub ahead of print | PMID: 25733384
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Abstract

Causes of Death and Heart Weights in Adults at Necropsy in a Tertiary Texas Hospital, 2013-2015.

Roberts WC, Won VS, Vasudevan A, Guileyardo JM
The causes of death and heart weights at death appear to be quite different in the USA today than in the first few decades of the last century. We determined the causes of death and heart weights at necropsy in 231 adults and compared the heart weights to those reported in several studies in the first half of the 20th century. Of the 231 patients, 91 (39%) died of a cardiovascular (CV) condition, and 140 (61%), of a non-CV condition. Of the 91 fatal CV disease cases, 48 had fatal coronary artery disease (CAD); of the remaining 183 cases without fatal CAD, 25 had narrowing >75% of 1 or more major epicardial coronary arteries. Thus, 73 of the 231 (32%) patients at necropsy had severe CAD. Comparison between the fatal CV and fatal non-CV cases disclosed variable age (mean 64 years vs mean 57 years) and heart weight (529 g vs 449 g) to be significantly different. Heart weight was found to be the only significantly variable between men and women. Comparison of the heart weights in this study to those recorded as "normal" hearts 75 to 115 years earlier showed that today\'s "average" heart is much larger than those reported earlier. In contrast to the earlier studies, heart weight presently appears to increase with age and with an increase in body mass index. In conclusion, early studies in heart weight did not take into account today\'s longer survival and therefore a high prevalence of systemic hypertension, diabetes mellitus, obesity (and cardiac adiposity), and the presence of atherosclerotic CAD. Additionally, the cause of death (CV vs non-CV) was rarely considered in the early studies of heart weight.

Am J Cardiol: 15 Oct 2016; epub ahead of print
Roberts WC, Won VS, Vasudevan A, Guileyardo JM
Am J Cardiol: 15 Oct 2016; epub ahead of print | PMID: 27743575
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Abstract

Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee Meeting Regarding Cangrelor.

Lhermusier T, Baker NC, Waksman R
Landmark clinical trials have established the benefit of P2Y12 inhibitors in the setting of acute coronary syndrome and percutaneous coronary intervention. On February 12, 2014, the Medicines Company (Sponsor) presented efficacy and safety data regarding cangrelor to the Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee. The Sponsor sought approval for 2 indications: (1) in the setting of percutaneous coronary intervention for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with coronary artery disease and (2) in the setting of bridging therapy in patients with acute coronary syndrome or with stents who are at increased risk for thrombotic events (such as stent thrombosis) when oral P2Y12 therapy is interrupted because of surgery. The following is a summary of the data presented to the FDA by the Sponsor, the FDA\'s clinical review of cangrelor.

Am J Cardiol: 01 Mar 2015; epub ahead of print
Lhermusier T, Baker NC, Waksman R
Am J Cardiol: 01 Mar 2015; epub ahead of print | PMID: 25728646
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Abstract

Gender-Related Cardiovascular Risk in Healthy Middle-Aged Adults.

Perelshtein Brezinov O, Kivity S, Segev S, Sidi Y, ... Maor E, Klempfner R
Men tend to develop cardiovascular disease (CVD) earlier in life than women. Whether this difference is attributable only to gender is a matter of debate. The purpose of this study was to evaluate gender differences in cardiovascular risk in a large cohort of asymptomatic men and women and explore gender-related risk in prespecified risk factor subgroups. We investigated 14,966 asymptomatic men and women free of diabetes, hypertension, or ischemic heart disease who were annually screened. The primary end point of the present study was the occurrence of ischemic or cerebrovascular disease as composite end point. Multivariate Cox proportional hazards regression modeling was used to assess the gender difference regarding CVD and to examine the association between CVD risk factors and gender. Mean age of the study population was 47 ± 10 years and 30% were women. Kaplan-Meier survival analysis showed that at 6.2 ± 3.9 years\' follow-up, the rate of CVD events was 6.1% among men compared with 1.8% among women (log-rank p <0.001). Consistently, multivariate analysis demonstrated that male gender was independently associated with a significant threefold increased risk for development of CVD events (hazard ratio 3.05, CI 2.25 to 4.14). The CVD risk associated with male gender was consistent in each risk subset analyzed, including older age, low high-density lipoprotein, impaired fasting glucose, and positive family history for ischemic heart disease (all p values for gender-by-risk factor interactions <0.05). Higher performance on treadmill test had a protective effect regarding CVD development in both men and women. In conclusions, healthy middle-aged men experienced increased risk for the development of CVD events compared with women independently of traditional CVD risk factors. However, better exercise capacity is associated with a protective effect.

Am J Cardiol: 13 Oct 2016; epub ahead of print
Perelshtein Brezinov O, Kivity S, Segev S, Sidi Y, ... Maor E, Klempfner R
Am J Cardiol: 13 Oct 2016; epub ahead of print | PMID: 27737731
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Abstract

Comparison of Usefulness of Exercise Testing Versus Coronary Computed Tomographic Angiography for Evaluation of Patients Suspected of Having Coronary Artery Disease.

Ovrehus KA, Jensen JK, Mickley HF, Munkholm H, ... Bøtker HE, Nørgaard BL
In patients suspected of having coronary artery disease (CAD), we compared the diagnostic sensitivity and specificity of exercise testing using ST-segment changes alone and ST-segment changes, angina pectoris, and hemodynamic variables compared to coronary computed tomographic angiography (CTA). Quantitative invasive coronary angiography was the reference method (>50% coronary lumen reduction). A positive exercise test was defined as the development of significant ST-segment changes (>/=1 mV measured 80 ms from the J-point), and the occurrence of one or more of the following criteria: ST-segment changes >/=1 mV measured 80 ms from the J-point, angina pectoris, ventricular arrhythmia (the occurrence of >/=3 premature ventricular beats), and >/=20 mm Hg decrease in systolic blood pressure during the test. Positive results on CTA were defined as a coronary lumen reduction of >/=50%. In 100 patients (61 +/- 9 years old, 50% men, and 29% prevalence of significant CAD), the diagnostic sensitivity and specificity of exercise testing using ST-segment changes was 45% (95% confidence interval 53% to 87%) and 63% (95% confidence interval 61% to 84%), respectively. However, the inclusion of all test variables yielded a sensitivity of 72% (95% confidence interval 53% to 87%) and a specificity of 37% (95% confidence interval 26% to 49%). The diagnostic sensitivity of 97% (95% confidence interval 82% to 100%) and specificity of 80% (95% confidence interval 69% to 89%) for CTA, however, were superior to any of the exercise test analysis strategies. In conclusion, in patients suspected of having CAD, the diagnostic sensitivity of exercise testing significantly improves if all test variables are included compared to using ST-segment changes exclusively. Furthermore, the superior diagnostic performance of CTA for the detection and exclusion of significant CAD might favor CTA as the first-line diagnostic test in patients suspected of having CAD.

Am J Cardiol: 09 Mar 2010; 105:773-779
Ovrehus KA, Jensen JK, Mickley HF, Munkholm H, ... Bøtker HE, Nørgaard BL
Am J Cardiol: 09 Mar 2010; 105:773-779 | PMID: 20211318
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Abstract

Relation Between End-Procedural Activated Clotting Time Values and Radial Artery Occlusion Rate With Standard Fixed-Dose Heparin After Transradial Cardiac Catheterization.

Maden O, Kafes H, Balci KG, Tola M, ... Balci MM, Kısacık HL
Although heparin administration has reduced the incidence of radial artery occlusion (RAO) during the transradial coronary angiography (TRCA), the effective activated clotting time (ACT) value for guiding unfractionated heparin dosing in patients undergoing TRCA is unknown. Four hundred thirty-two patients who were scheduled for elective TRCA were enrolled in our prospective study. All the patients received a standard dose of 5,000 IU unfractionated heparin. Anticoagulation level was assessed by ACT measurements that were taken at the end of the procedure just before the sheath removal. The day after TRCA, all patients were evaluated by color Doppler ultrasound to detect RAO. RAO was found in 29 patients (6.7%). A median ACT of 205 seconds in the RAO group and 265 seconds in the radial artery patent group were detected (p <0.001). Mean procedure duration was significantly longer in the RAO group than in the radial artery patent group (18.55 ± 9.80 vs 11.24 ± 7.07 minutes, p <0.001). There was a negative correlation between end-procedural ACT and procedure duration (r = -0.117, p = 0.015). In multivariate analysis, end-procedural ACT (odds ratio 0.981, 95% confidence interval [CI] 0.972 to 0.989, p <0.001), procedure duration (odds ratio 1.076, 95% CI, 1.037 to 1.116, p <0.001), and radial artery diameter (odds ratio 0.240, 95% CI 0.063 to 0.907, p = 0.035) were found as independent predictors of RAO. In conclusion, shorter end-procedural ACT levels, longer procedural duration, and smaller radial arterial diameter were independently associated with RAOs after TRCA with standard-dose heparin. In prolonged procedures, ACT-based heparin dosing may be useful to overcome RAO.

Am J Cardiol: 19 Sep 2016; epub ahead of print
Maden O, Kafes H, Balci KG, Tola M, ... Balci MM, Kısacık HL
Am J Cardiol: 19 Sep 2016; epub ahead of print | PMID: 27645762
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Abstract

Structural Alterations of Retinal Arterioles in Adults Late After Repair of Aortic Isthmic Coarctation.

Pressler A, Esefeld K, Scherr J, Ali M, ... Schmidt-Trucksäss A, Hager A
Patients after coarctation repair still have an increased risk of cardiovascular or cerebrovascular events. This has been explained by the persisting hypertension and alterations in the peripheral vessels. However, involvement of the central vessels such as the retinal arteries is virtually unknown. A total of 34 patients after coarctation repair (22 men and 12 women; 23 to 58 years old, age range 0 to 32 years at surgical repair) and 34 nonhypertensive controls underwent structural and functional retinal vessel analysis. Using structural analysis, the vessel diameters were measured. Using functional analysis, the endothelium-dependent vessel dilation in response to flicker light stimulation was assessed. In the patients after coarctation repair, the retinal arteriolar diameter was significantly reduced compared to that of the controls (median 182 mum, first to third quartile 171 to 197; vs 197 mum, first to third quartile 193 to 206; p <0.001). These findings were independent of the peripheral blood pressure and age at intervention. No differences were found for venules. The functional analysis findings were not different between the patients and controls (maximum dilation 3.5%, first to third quartile 2.1% to 4.5% vs 3.6%, first to third quartile 2.2% to 4.3%; p = 0.81), indicating preserved autoregulative mechanisms. In conclusion, the retinal artery diameter is reduced in patients after coarctation repair, independent of their current blood pressure level and age at intervention. As a structural marker of chronic vessel damage associated with past, current, or future hypertension, retinal arteriolar narrowing has been linked to stroke incidence. These results indicate an involvement of cerebral microcirculation in aortic coarctation, despite timely repair, and might contribute to explain the increased rate of cerebrovascular events in such patients.

Am J Cardiol: 26 Feb 2010; 105:740-744
Pressler A, Esefeld K, Scherr J, Ali M, ... Schmidt-Trucksäss A, Hager A
Am J Cardiol: 26 Feb 2010; 105:740-744 | PMID: 20185026
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Abstract

Meta-Analysis of Relation of Epicardial Adipose Tissue Volume to Left Atrial Dilation and to Left Ventricular Hypertrophy and Functions.

Mancio J, Azevedo D, Fragao-Marques M, Falcao-Pires I, ... Fontes-Carvalho R, Bettencourt N
Many studies have explored the hypothesis that epicardial adipose tissue (EAT) accumulation adversely affects cardiac remodeling. We assessed, through a systematic review and meta-analysis, whether EAT is linked to left atrial (LA) and left ventricular (LV) structure and function, irrespective of global or abdominal visceral adiposity. We searched MEDLINE, Scopus, and Web of Science for studies evaluating the association of EAT volume quantified by computed tomography with cardiac morphology and function. We used DerSimonian and Laird random-effects models to summarize the adjusted-effect of 10 ml variation of EAT on LA size, LV mass, LV diastolic and systolic functions parameters, and presence of diastolic dysfunction. We quantified heterogeneity using I statistic. We included 19 studies. Quantitative analysis by cardiac parameters, including LA dimension (n = 2,719), LV mass (n = 2,519), diastolic function (n = 3,741), and systolic function (n = 2,037) showed that EAT was associated with LA dilation (pooled B-coefficient: 0.12 mm; 95% confidence interval [CI] 0.08 to 0.17; I: 97%), LV hypertrophy (pooled B-coefficient: 1.21 g; 95% CI 0.63 to 1.79; I: 77%), diastolic dysfunction (odds ratio: 1.35; 95% CI 1.16 to 1.57; I: 0%), higher E/E\' ratio (pooled B-coefficient: 0.28 cm/s; 95% CI 0.08 to 0.49; I: 67%), lower E\' velocity (pooled B-coefficient: -0.16 cm/s; 95% CI -0.22 to -0.09; I: 43%), and E/A ratio (pooled B-coefficient: -0.01; 95% CI -0.02 to -0.001; I: 70%), independently of body mass index. There was no association between EAT and LV systolic function. In conclusion, EAT volume measured by computed tomography was independently associated with LA dilation, LV hypertrophy, and diastolic dysfunction.

Am J Cardiol: 05 Nov 2018; epub ahead of print
Mancio J, Azevedo D, Fragao-Marques M, Falcao-Pires I, ... Fontes-Carvalho R, Bettencourt N
Am J Cardiol: 05 Nov 2018; epub ahead of print | PMID: 30477802
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Abstract

Usefulness of Coronary Pressure Measurement for Functional Evaluation of Drug-Eluting Stent Restenosis.

Nam CW, Rha SW, Koo BK, Doh JH, ... Choi CU, Oh DJ
Despite the widespread adoption of drug-eluting stent (DES) implantation, the optimal treatment of DES failures remains challenging. The present study evaluated the relation between quantitative angiography and the fractional flow reserve (FFR) in restenotic lesions after DES implantation and the efficacy of FFR in determining whether to treat these lesions. To assess their functional significance, the coronary pressure-derived FFR was measured in 50 DES restenotic lesions (49 patients). Additional intervention was performed in lesions with a FFR <0.8. Major adverse cardiac events were assessed at 12 months after the reintervention procedure. The mean percent diameter stenosis (%DS) was 58 ± 13%. Of the 50 lesions, 20 (40%) were deferred without additional intervention. The FFR and %DS had a negative correlation (r = -0.61, p <0.001). However, when only the lesions with diffuse-type restenosis (15 lesions) were analyzed, the degree of correlation decreased (r = -0.56, p = 0.12). Although most lesions (89%) with a %DS of ≥70 had significant functional ischemia, among 41 lesions with a %DS <70, only 20 (49%) had demonstrated functional patency. The incidence of adverse events during the 12 months of follow-up after FFR-guided treatment was 18.0% (23.3% in the FFR <0.80 group and 10.0% in FFR ≥0.80 group). In conclusion, a discrepancy was found between functional ischemia measured by the FFR and the angiographic %DS, in particular, in moderate- or diffuse-type restenotic lesions after DES implantation. The outcome of FFR-guided deferral in patients with DES in-stent restenosis seems favorable.

Am J Cardiol: 12 Apr 2011; epub ahead of print
Nam CW, Rha SW, Koo BK, Doh JH, ... Choi CU, Oh DJ
Am J Cardiol: 12 Apr 2011; epub ahead of print | PMID: 21481824
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Abstract

Long-Term Clinical Outcomes of Percutaneous Coronary Intervention for Chronic Total Occlusions in Patients With Versus Without Diabetes Mellitus.

Claessen BE, Dangas GD, Godino C, Lee SW, ... Mehran R, Multinational Cto Registry
There is a paucity of data on long-term outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) in the high-risk group of patients with diabetes mellitus (DM). The aim of this study was to evaluate long-term clinical outcomes after PCI of CTOs in patients with and without DM. A total of 1,742 patients with known DM status underwent PCI of CTOs at 3 tertiary care centers in the United States, South Korea, and Italy from 1998 to 2007. Five-year clinical outcomes were evaluated in patients with successful versus failed CTO PCI and the use of drug-eluting stents (DES) versus bare-metal stents (BMS) stratified according to DM status. A total of 395 patients (23%) had DM (42% of whom had insulin-dependent DM). Procedural success was similar in patients with versus without DM (69.6% vs 67.9%, p = 0.53). After successful CTO PCI, stents were implanted in 96.4% of patients with DM (BMS in 23.8%, DES in 76.2%) and in 94.0% of patients without DM (BMS in 38.6%, DES in 61.4%). Median follow-up was 3.0 years. In patients with DM, successful CTO PCI was associated with reduced long-term mortality (10.4% vs 13.0%, p <0.05) and a reduced need for coronary artery bypass grafting (2.4% vs 15.7%, p <0.01). The use of DES was associated with a reduction in target vessel revascularization in patients with DM (14.8% vs 54.1%, p <0.01) and in those without DM (17.6% vs 26.5%, p <0.01). Multivariate analysis identified insulin-dependent DM as an independent predictor of mortality in the DM cohort. In conclusion, successful CTO PCI in patients with DM was associated with a reduction in mortality and the need for coronary artery bypass grafting. Compared to non-insulin-dependent DM, patients with insulin-dependent DM had an increased risk for long-term mortality. The use of DES rather than BMS was associated with a reduction in target vessel revascularization in patients with and without DM.

Am J Cardiol: 08 Aug 2011; epub ahead of print
Claessen BE, Dangas GD, Godino C, Lee SW, ... Mehran R, Multinational Cto Registry
Am J Cardiol: 08 Aug 2011; epub ahead of print | PMID: 21820095
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Abstract

Analysis of the Bypass Angioplasty Revascularization Investigation Trial Using a Multistate Model of Clinical Outcomes.

Zhang X, Li Q, Rogatko A, Tighiouart M, ... Kaul S, Bairey Merz CN
Current cardiovascular randomized trials typically use composite outcomes. We hypothesized that the Bypass Angioplasty Revascularization Investigation (BARI) outcomes and conclusions would differ using a multistate model relative to the intervention for the composite outcome of death (D) and nonfatal Q-wave myocardial infarction (MI). We used a multistate model which uses transition paths to simultaneously assess multiple end points. Using the 10-year follow-up BARI data, we post hoc analyzed outcomes according to 3 transition paths: (1) from intervention to MI; (2) from intervention to death; and (3) from MI to death. Of 1,829 patients randomized to the intervention of percutaneous transluminal coronary angioplasty or coronary artery bypass grafting (CABG), 700 (38%) experienced the composite event D/MI which included 230 (13%) nonfatal MI and 470 (26%) death without antecedent nonfatal MI, whereas 79 of 230 (34%) experienced death after nonfatal MI. Outcomes of the 3 individual transition paths were analyzed by a multistate model. In contrast to standard survival analyses, after adjustment for baseline clinical covariates, outcomes after percutaneous transluminal coronary angioplasty or CABG were not significantly different for intervention to MI (p = 0.33) or intervention to death (p = 0.23), but MI to death favored CABG (p = 0.02). Deconstruction of the BARI data using a multistate model identifies a significant difference in individual transition-stage outcomes and therefore trial conclusions in contrast to the standard methods of survival analysis. These observations suggest multistate models should be considered in the design and analysis of randomized cardiovascular trials which use composite outcomes.

Am J Cardiol: 27 Feb 2015; epub ahead of print
Zhang X, Li Q, Rogatko A, Tighiouart M, ... Kaul S, Bairey Merz CN
Am J Cardiol: 27 Feb 2015; epub ahead of print | PMID: 25724784
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Abstract

Prognostic Impact of Clopidogrel Pretreatment in Patients With Acute Coronary Syndrome Managed Invasively.

Almendro-Delia M, Gonzalez-Torres L, Garcia-Alcantara Á, Reina-Toral A, ... García Rubira JC, ARIAM-Andalucía Group
Pretreatment with antiP2Y12 agents before angiography in acute coronary syndrome (ACS) is associated with a reduction in thrombotic events. However, recent evidences have questioned the benefits of upstream antiP2Y12, reporting a higher incidence of bleeding. We analyzed the prognostic impact of clopidogrel pretreatment in a large cohort of invasively managed patients with ACS. In hospital, safety and efficacy of clopidogrel pretreatment were retrospectively analyzed in patients included in the ARIAM-Andalucía Registry (Analysis of Delay in Acute Myocardial Infarction). Propensity score and inverse probability of treatment weighting analysis were performed to control treatment selection bias. Results were stratified by ACS type. Sensitivity analyses were used to explore stability of the overall treatment effect. Of 9,621 patients managed invasively, 69% received clopidogrel before coronary angiography. In the ST-elevation myocardial infarction group, pretreatment was associated with a significant reduction in reinfarction (odds ratio 0.53, 95% confidence interval [CI] 0.27 to 0.96; p = 0.027), stent thrombosis (odds ratio 0.15, 95% CI 0.06 to 0.38; p <0.0001), and mortality (odds ratio 0.67, 95% CI 0.48 to 0.94; p = 0.020), with an increase in minor bleeding but remained as a net clinical benefit strategy. Those benefits were not present in patients without ST elevation (non-ST elevation ACS). The weighting and propensity analysis confirmed the same results. An interaction between pretreatment duration and bleeding was observed. In conclusion, pretreatment with clopidogrel reduced the occurrence of death and thrombotic outcomes at the cost of minor bleeding. Those benefits exclusively affected ST-elevation myocardial infarction cases. The potential benefit of routine upstream pretreatment in patients with non-ST-elevation ACS should be reappraised at the present.

Am J Cardiol: 01 Mar 2015; epub ahead of print
Almendro-Delia M, Gonzalez-Torres L, Garcia-Alcantara Á, Reina-Toral A, ... García Rubira JC, ARIAM-Andalucía Group
Am J Cardiol: 01 Mar 2015; epub ahead of print | PMID: 25728644
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Abstract

Infective Endocarditis Involving the Pulmonary Valve.

Miranda WR, Connolly HM, DeSimone DC, Phillips SD, ... Steckelberg JM, Baddour LM
Pulmonary valve (PV) infective endocarditis (IE) is a rare entity, accounting for 1.5% to 2% of cases of IE. Published data are limited to a few case series and reports. We sought to review the Mayo Clinic experience and describe clinical, echocardiographic, and microbiologic features. We included all patients aged ≥18 years seen from 2000 to 2014 who had a diagnosis of native PV IE and unequivocal echocardiographic involvement of the PV. Nine patients with PV IE were identified. Isolated PV IE was present in 7 (78%) of 9 cases. The median age was 59 years and 22% were women. Three patients had congenital heart disease, 2 had central venous catheters, and 3 had cardiovascular implantable electronic devices. Five patients (56%) received chronic immunosuppressive therapy. Enterococcus faecalis and viridans group streptococci were the most common pathogens, isolated in 22% of cases each. Transthoracic echocardiogram (TTE) and transesophageal echocardiogram (TEE) were done in 6 and 7 patients, respectively. Four patients underwent both procedures. TTE was diagnostic in all cases, but TEE failed to detect PV involvement in 1 patient. Median follow-up was 1.8 years. Five patients (56%) underwent PV replacement. There were no operative deaths. One patient had sudden death during follow-up, unrelated to his PV IE episode. Our results suggest that PV IE is rare but carries significant morbidity. TTE and TEE provide complementary information with TEE providing better visualization of other cardiac structures. Our findings of a high prevalence of immunosuppressive therapy and cardiovascular implantable electronic devices have not been previously reported and deserve further investigation.

Am J Cardiol: 26 Nov 2015; 116:1928-31
Miranda WR, Connolly HM, DeSimone DC, Phillips SD, ... Steckelberg JM, Baddour LM
Am J Cardiol: 26 Nov 2015; 116:1928-31 | PMID: 26611123
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Abstract

Meta-Analysis Comparing Complete Revascularization Versus Infarct-Related Only Strategies for Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Artery Disease.

Shah R, Berzingi C, Mumtaz M, Jasper JB, ... Ramanathan KB, Rao SV
Several recent randomized controlled trials (RCTs) demonstrated better outcomes with multivessel complete revascularization (CR) than with infarct-related artery-only revascularization (IRA-OR) in patients with ST-segment elevation myocardial infarction. It is unclear whether CR should be performed during the index procedure (IP) at the time of primary percutaneous coronary intervention (PCI) or as a staged procedure (SP). Therefore, we performed a pairwise meta-analysis using a random-effects model and network meta-analysis using mixed-treatment comparison models to compare the efficacies of 3 revascularization strategies (IRA-OR, CR-IP, and CR-SP). Scientific databases and websites were searched to find RCTs. Data from 9 RCTs involving 2,176 patients were included. In mixed-comparison models, CR-IP decreased the risk of major adverse cardiac events (MACEs; odds ratio [OR] 0.36, 95% CI 0.25 to 0.54), recurrent myocardial infarction (MI; OR 0.50, 95% CI 0.24 to 0.91), revascularization (OR 0.24, 95% CI 0.15 to 0.38), and cardiovascular (CV) mortality (OR 0.44, 95% CI 0.20 to 0.87). However, only the rates of MACEs, MI, and CV mortality were lower with CR-SP than with IRA-OR. Similarly, in direct-comparison meta-analysis, the risk of MI was 66% lower with CR-IP than with IRA-OR, but this advantage was not seen with CR-SP. There were no differences in all-cause mortality between the 3 revascularization strategies. In conclusion, this meta-analysis shows that in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease, CR either during primary PCI or as an SP results in lower occurrences of MACE, revascularization, and CV mortality than IRA-OR. CR performed during primary PCI also results in lower rates of recurrent MI and seems the most efficacious revascularization strategy of the 3.

Am J Cardiol: 18 Sep 2016; epub ahead of print
Shah R, Berzingi C, Mumtaz M, Jasper JB, ... Ramanathan KB, Rao SV
Am J Cardiol: 18 Sep 2016; epub ahead of print | PMID: 27642115
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