American Heart Journal

Triple antithrombotic therapy after coronary stenting in the elderly with atrial fibrillation: Necessary or too hazardous?

Freek W.A. Verheugt — 2012-04-01

Dual antiplatelet therapy has become the cornerstone of the treatment for patients undergoing coronary stenting and of those with acute coronary syndromes with or without stent implantation. Although there is consensus about the indication for dual antiplatelet therapy, there is little evidence about the optimal duration of therapy. In patients surviving non–ST-segment elevation acute coronary syndromes, 1 year of treatment is advised. Cardiologists prefer longer dual antiplatelet therapy rather than single antiplatelet medication (aspirin alone) in patients with drug-eluting stents when compared with carriers of bare metal stents. Consequently, many patients in the cardiology practice in 2012 are on dual antiplatelet therapy, mainly aspirin and clopidogrel. The only important side effect of dual antiplatelet therapy is increased bleeding in comparison with aspirin alone. This has been established in the large trials with clopidogrel in acute coronary syndromes and therafter as well as in atrial fibrillation. Especially in the latter, dual antiplatelet therapy has shown to be as hazardous as oral anticoagulation. Special attention of the risks of dual antiplatelet therapy has been given to patients awaiting coronary artery bypass surgery. Clopidogrel on top of aspirin has been associated with significantly increased blood loss during coronary surgery when compared with aspirin alone. However, this excess bleeding was not significantly associated with an increased risk of reoperation or mortality. Yet, it is generally advised to discontinue clopidogrel 5 days ahead of coronary surgery. Little is known, however, about the optimal strategy in patients on dual antiplatelet therapy undergoing other forms of surgery such as abdominal surgery, orthopedic procedures, neurosurgical operations, or procedures in other vital organs where bleeding can result in organ loss.

Rationale and design of a Global Rheumatic Heart Disease Registry: The REMEDY study

2012-03-13

Background: Rheumatic heart disease (RHD) is the principal cause of valvular heart disease–related mortality and morbidity in low- and middle-income countries. The disease predominantly affects children and young adults. It is estimated that RHD may potentially be responsible for 1.4 million deaths annually worldwide and 7.5% of all strokes occurring in developing countries. Despite the staggering global burden, there are no contemporary data documenting the presentation, clinical course, complications, and treatment practices among patients with RHD.Methods: The REMEDY study is a prospective, international, multicenter, hospital-based registry planned in 2 phases: the vanguard phase involving centers in Africa and India will enrol 3,000 participants with RHD over a 1-year period. We will document clinical and echocardiographic characteristics of patients at presentation. Over a 2-year follow-up, we will document disease progression and treatment practices with particular reference to adherence to secondary prophylaxis and oral anticoagulation regimens. With 3,000 patients, we will be able to reliably determine the incidence of all-cause mortality, worsening heart failure requiring hospitalization, systemic embolism (including stroke), and major bleeding individually among all participants. We will identify barriers to care in a subgroup of 500 patients.Conclusion: The REMEDY study will provide comprehensive, contemporary data on patients with RHD and will help in the development of strategies to prevent and manage RHD and its complications.

Target temperature management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design

2012-04-01

Background: Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32°C to 34°C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known.Methods: The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33°C or 36°C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm.Discussion: The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.

Design and rationale for the PREVAIL study: Effect of e-Health individually tailored encouragements to physical exercise on aerobic fitness among adolescents with congenital heart disease—a randomized clinical trial

2012-04-01

Intensive exercise may be an important part of rehabilitation in patients with congenital heart disease (CHD). However, performing regular physical exercise is challenging for many adolescent patients. Consequently, effective exercise encouragements may be needed. Little is known on the effect of e-Health encouragements on physical fitness, physical activity, and health-related quality of life in adolescents.This trial is a nationwide interactive e-Health rehabilitation study lasting 1 year, centered on interactive use of mobile phone and Internet technology. We hypothesize that e-Health encouragements and interactive monitoring of intensive exercise for 1 year can improve physical fitness, physical activity, and health-related quality of life.Two hundred sixteen adolescents (age, 13-16 years) with surgically corrected complex CHD but without significant hemodynamic residual defects and no restrictions to participate in physical activity are in the process of being enrolled by invitation after informed consent.Physical fitness is measured as the maximal oxygen uptake (Vo2) at baseline and after 12 months by an assessor blinded to the randomization group. After baseline testing, the patients are 1:1 randomized to an intervention group or a control group.Individually fully automated tailored e-Health encouragements—SMS, Internet, and mobile applications—aimed at increasing physical activity are delivered to the participants in the intervention group once a week. The Bandura's Social Cognitive Theory inspires the behavioral theoretical background. The e-Health intervention and the Godfrey cycle ergometer protocol have been feasibility tested and seem applicable to adolescents with CHD. The trial is expected to contribute with new knowledge regarding how physical activity in adolescents with CHD can be increased and, possibly, comorbidity be reduced.

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): Rationale and study design of a randomized multicenter trial in a Dutch all-comers population

2012-04-01

Background: Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity.Methods: DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up.Summary: DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES.

Reinfarction after percutaneous coronary intervention or medical management using the universal definition in patients with total occlusion after myocardial infarction: Results from long-term follow-up of the Occluded Artery Trial (OAT) cohort

2012-04-01

Background: The OAT study randomized 2,201 patients with a totally occluded infarct-related artery on days 3 to 28 (>24 hours) after myocardial infarction (MI) to percutaneous coronary intervention (PCI) or medical treatment (MED). There was no difference in the primary end point of death, reinfarction, or heart failure at 2.9 or 6-year mean follow-up. However, in patients randomized to PCI, there was a trend toward a higher rate of reinfarction.Methods: We analyzed the characteristics and types of reinfarction according to the universal definition. Independent predictors of reinfarction were determined using Cox proportional hazard models with follow-up up to 9 years.Results: There were 169 reinfarctions: 9.4% PCI vs 8.0% MED, hazard ratio 1.31, 95% CI 0.97-1.77, P = .08. Spontaneous reinfarction (type 1) occurred with similar frequency in the groups: 4.9% PCI vs 6.7% MED, hazard ratio 0.78, 95% CI 0.53-1.15, P = .21. Rates of type 2 (secondary) and 3 (sudden death) MI were similar in both groups. There was an increase in type 4a reinfarctions (related to protocol or other PCI) (0.8% PCI vs 0.1% MED, P = .01) and type 4b reinfarctions (stent thrombosis) (2.7% PCI vs 0.6% MED, P < .001).Multivariate predictors of reinfarction were history of PCI before study entry (P = .001), diabetes (P = .005), and absence of new Q waves with the index infarction (P = .01).Conclusions: There was a trend for reinfarctions to be more frequent with PCI. Opening an occluded infarct-related artery in stable patients with late post-MI may expose them to a risk of subsequent reinfarction related to reocclusion and stent thrombosis.

Differences in symptom presentation and hospital mortality according to type of acute myocardial infarction

2012-03-30

Background: Chest pain/discomfort (CP) is the hallmark symptom of acute myocardial infarction (MI), but some patients with MI present without CP. We hypothesized that MI type (ST-segment elevation MI [STEMI] or non-STEMI [NSTEMI]) may be associated with the presence or absence of CP.Methods: We investigated the association between CP at presentation and MI type, hospital care, and mortality among 1,143,513 patients with MI in the National Registry of Myocardial Infarction (NRMI) from 1994 to 2006.Results: Overall, 43.6% of patients with NSTEMI and 27.1% of patients with STEMI presented without CP. For both MI type, patients without CP were older, were more frequently female, had more diabetes or history of heart failure, were more likely to delay hospital arrival, and were less likely to receive evidence-based medical therapies and invasive cardiac procedures. Multivariable analysis indicated that NSTEMI (vs STEMI) was the strongest predictor of atypical symptoms (adjusted odds ratio [95% CI], 1.93 [1.91-1.95]). Within the 4 CP/MI type categories, hospital mortality was highest for no CP/STEMI (27.8%), followed by no CP/NSTEMI (15.3%) and CP/STEMI (9.6%), and was lowest for CP/NSTEMI (5.4%). The adjusted odds ratio of mortality was 1.38 (1.35-1.41) for no CP (vs CP) in the STEMI group and 1.31 (1.28-1.34) in the NSTEMI group.Conclusions: Hospitalized patients with NSTEMI were nearly 2-fold more likely to present without CP than patients with STEMI. Patients with MI without CP were less quickly diagnosed and treated and had higher adjusted odds of hospital mortality, regardless of whether they had ST-segment elevation.

Heart rate recovery in pulmonary arterial hypertension: Relationship with exercise capacity and prognosis

2012-04-01

Background: Delayed postexercise heart rate recovery (HRR) has been associated with disability and poor prognosis in chronic cardiopulmonary diseases. The usefulness of HRR to predict exercise impairment and mortality in patients with pulmonary arterial hypertension (PAH), however, remains largely unexplored.Methods: Seventy-two patients with PAH of varied etiology (New York Heart Association classes I-IV) and 21 age- and gender-matched controls underwent a maximal incremental cardiopulmonary exercise test (CPET), with heart rate being recorded up to the fifth minute of recovery.Results: Heart rate recovery was consistently lower in the patients compared with the controls (P < .05). The best cutoff for HRR in 1 minute (HRR1min) to discriminate the patients from the controls was 18 beats. Compared with patients with HRR1min ≤18 (n = 40), those with HRR1min >18 (n = 32) had better New York Heart Association scores, resting hemodynamics and 6-minute walking distance. In fact, HRR1min >18 was associated with a range of maximal and submaximal CPET variables indicative of less severe exercise impairment (P < .05). The single independent predictor of HRR1min ≤18 was the 6-minute walking distance (odds ratio [95% CI] 0.99 [0.98-1.00], P < .05). On a multiple regression analysis that considered only CPET-independent variables, HRR1min ≤18 was the single predictor of mortality (hazard ratio [95% CI] 1.19 [1.03-1.37], P < .05).Conclusions: Preserved HRR1min (>18 beats) is associated with less impaired responses to incremental exercise in patients with PAH. Conversely, a delayed HRR1min response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated (and costlier) analyses provided by a full CPET are not available.

Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension

2012-04-01

Background: Accurate measurement of left ventricular filling pressure is important to distinguish between category 1 pulmonary arterial hypertension (PAH) and category 2 pulmonary hypertension (PH) from left heart diseases (PH-HFpEF). We hypothesized that the common practice of relying on the digitized mean pulmonary capillary wedge pressure (PCWP-digital) results in erroneous recordings, whereas end-expiratory PCWP measurements (PCWP–end Exp) provide a reliable surrogate measurement for end-expiratory left ventricular end-diastolic pressure (LVEDP–end Exp–end Exp).Methods: We prospectively performed left and right cardiac catheterization on 61 patients referred for evaluation of PH and compared the LVEDP–end Exp to end-expiration to the (a) PCWP–end Exp and (b) PCWP-digital.Results: The PCWP–end Exp was a more reliable reflection of LVEDP–end Exp (mean 13.2 mm Hg vs 12.4 mm Hg; P, nonsignificant) than PCWP-digital (mean 8.0 mm Hg vs 12.4 mm Hg, P < .05). Bland-Altman analysis of PCWP-digital and LVEDP–end Exp revealed a mean bias of −4.4 mm Hg with 95% limits of agreement of −11.3 to 2.5 mm Hg. Bland-Altman analysis of PCWP–end Exp and LVEDP–end Exp revealed a mean bias of 0.9 mm Hg with 95% limits of agreement of −5.2 to 6.9 mm Hg. If PCWP-digital were used to define LVEDP–end Exp, 14 (27%) of 52 patients would have been misclassified as having PAH rather than PH-HFpEF. Patients with obesity and hypoxia were particularly more likely to be misclassified as PAH instead of PH-HFpEF if PCWP-digital was used to define LVEDP–end Exp (odds ratio 8.1, 95% CI 1.644-40.04, P = .01).Conclusions: The common practice of using PCWP-digital instead of PCWP–end Exp results in a significant underestimation of LVEDP–end Exp. In our study, this translated to nearly 30% of patients being misclassified as having PAH rather than PH from HFpEF.

Use of a highly sensitive assay for cardiac troponin T and N-terminal pro-brain natriuretic peptide to diagnose acute rejection in pediatric cardiac transplant recipients

2012-04-01

Background: Biomarkers have been proposed to augment or replace endomyocardial biopsy (EMB) to diagnose acute transplant rejection (AR). A new, highly sensitive assay for troponin T detects levels of cardiac troponin T (cTnT) 10- to 100-fold lower than standard assays but has not been investigated in transplant patients. N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been evaluated in pediatric transplant patients. The purpose of this pilot study was to evaluate the association of cTnT and NT-proBNP with AR in pediatric cardiac transplant patients.Methods: Plasma was obtained at the time of EMB from pediatric patients ≥1 year old. N-terminal pro-brain natriuretic peptide was measured in fresh plasma at the time of biopsy, and cTnT was measured from frozen, stored samples using the highly sensitive assay for troponin T. Biomarker data were correlated with EMB results. Cellular AR was defined as an International Society for Heart and Lung Transplantation biopsy score of grade ≥2R.Results: Fifty-three blood samples were obtained from 42 patients (mean age 11 years). Seven episodes of AR occurred in 5 patients. Biopsies with vs without AR were associated with higher cTnT (median [interquartile range {IQR}] 66 [45-139] vs 7 [2-13] pg/mL, P = .001) and NT-proBNP (median [IQR] 11,169 [280-23,317] vs 334 [160-650] pg/mL, P < .01). After successful treatment of AR in 5 patients, cTnT fell markedly (median [IQR] 53.5 [44.8-66.5] to 10.7 [1.5-16.4], P = .05).Conclusion: In this pilot study, we found marked elevation of cTnT and NT-proBNP among children with AR. Moreover, reduction in cTnT levels after treatment paralleled improvement in EMB results. If these findings are confirmed in larger prospective studies, monitoring with these biomarkers may obviate surveillance EMB.

ComparisOn of neointimal coVerage betwEen zotaRolimus-eluting stent and everolimus-eluting stent using Optical Coherence Tomography (COVER OCT)

2012-04-01

Background: Data on strut surface coverage of second-generation drug-eluting stents (DES) are limited. We investigated stent strut coverage of resolute zotarolimus-eluting stent (ZES-R) or everolimus-eluting stent (EES) at 9 months after implantation using optical coherence tomography (OCT).Methods: ComparisOn of neointimal coVerage betwEen zotaRolimus-eluting stent and everolimus-eluting stent using Optical Coherence Tomography (COVER OCT) is a prospective, randomized, multicenter trial comparing ZES-R to EES using OCT at 9 months after stent implantation. The primary end point was the rate of stent strut coverage at 9 months.Results: A total of 51 patients were randomized to receive either ZES-R (ZES-R group) or EES (EES group), and 47 stents (24 ZES-R and 23 EES) in 44 of 51 patients were evaluated by OCT both immediately after stent implantation and at 9 months. The neointimal thickness was not significantly different between the 2 groups at 9 months (ZES-R vs EES: 139 ± 58 vs 124 ± 42 μm, P = .31). The mean percentages of uncovered stent struts were 3.3% for ZES-R versus 3.4% for EES at 9 months (P = .51). The proportions of malapposed struts immediately after stent implantation (P = .89) and at 9-month follow-up (P = .34) were 0.8% and 0.7% for ZES-R versus 1.0% and 0.1% for EES, respectively. Thrombi were documented in 1 stent (1 [4.2%] in ZES-R vs 0 [0%] in EES).Conclusion: According to the sequential OCT evaluation, ZES-R and EES showed comparable neointimal thickness and the rate of uncovered stent strut at 9 months after stent implantation.

Effect of strut thickness on neointimal atherosclerotic change over an extended follow-up period (≥4 years) after bare-metal stent implantation: Intracoronary optical coherence tomography examination

2012-04-01

Background: Neointima inside the bare-metal stents (BMSs) can transform into atherosclerotic tissue during an extended follow-up because of a persistent inflammatory reaction to the metal. We sought to investigate whether strut thickness may impact on the atherosclerotic change in neointima 4 years or more after BMS implantation using optical coherence tomography.Methods: Forty-six stented lesions of 41 patients with BMS ≥4 years after implantation who underwent optical coherence tomography were enrolled in the study. The strut was defined as thin when less than 100 μm and thick when ≥100 μm. According to these criteria, stents were divided into 2 groups (thin strut n = 19, thick strut n = 27). Neointimal tissue was categorized into normal neointima, characterized by a signal-rich band without signal attenuation, or lipid-laden intima, with marked signal attenuation and a diffuse border. Intimal disruption, thrombus, and neovascularization were also evaluated.Results: The mean period after implantation was 98.2 ± 25.8 months in the thin-strut group and 91.1 ± 22.8 months in the thick-strut group (P = .330). Lipid-laden intima (70% vs 32%, P = .016), thin-cap fibroatheroma–like intima (59% vs 16%, P = .0056), and intimal disruption (48% vs 16%, P = .031) were observed more frequently in the thick-strut group than in the thin-strut group, but no significant difference was observed in the frequency of thrombus. Although peristrut neovascularization was a common finding in both groups (thick vs thin 81% vs 79%, P = 1.000), the frequency of intraintima neovascularization tended to be higher in the thick-strut group (67% vs 42%, P = .135).Conclusions: A thinner strut thickness may have favorable effects on neointimal atherosclerotic changes after BMS implantation.

Use and overuse of left ventriculography

2012-03-30

Background: Left ventriculography provided the first imaging of left ventricular function and was historically performed as part of coronary angiography despite a small but significant risk of complications. Because modern noninvasive imaging techniques are more accurate and carry smaller risks, the routine use of left ventriculography is of questionable utility. We sought to analyze the frequency that left ventriculography was performed during coronary angiography in patients with and without a recent alternative assessment of left ventricular function.Methods: We performed a retrospective analysis of insurance claims data from the Aetna health care benefits database including all adults who underwent coronary angiography in 2007. The primary outcome was the concomitant use of left ventriculography during coronary angiography.Results: Of 96,235 patients who underwent coronary angiography, left ventriculography was performed in 78,705 (81.8%). Use of left ventriculography was high in all subgroups, with greatest use in younger patients, those with a diagnosis of coronary disease, and those in the Southern United States. In the population who had undergone a very recent ejection fraction assessment by another modality (within 30 days) and who had had no intervening diagnosis of new heart failure, myocardial infarction, hypotension, or shock (37,149 patients), left ventriculography was performed in 32,798 patients (88%)—a rate higher than in the overall cohort.Conclusions: Left ventriculography was performed in most coronary angiography cases and often when an alternative imaging modality had been recently completed. New clinical practice guidelines should be considered to decrease the overuse of this invasive test.

An intravascular ultrasound appraisal of atherosclerotic plaque distribution in diseased coronary arteries

2012-04-01

Background: The assumption that atherosclerosis accumulates in the proximal coronary arteries and that distal segments are spared has yet to be systematically shown in vivo.Methods: We used intravascular ultrasound to analyze complete proximal, mid, and distal segments from 75 diseased left anterior descending arteries (LADs) and 61 diseased right coronary arteries (RCAs) (including either the posterolateral [PLA; n = 38] or posterior descending artery [PDA; n = 23]) to document that distal coronary arteries are more often free of disease vs proximal vessels. External elastic membrane, lumen, and plaque and media areas were measured every 0.4 mm (median), and plaque burden (plaque and media/external elastic membrane) and percentage of normal (plaque and media thickness <0.3 mm) cross sections/segment were determined.Results: Left anterior descending artery plaque was heaviest in proximal and mid segments, diminishing significantly in distal segments; plaque burden was 46% ± 9% in proximal, 39% ± 8% in mid, and 31% ± 9% in distal LAD (P < .0001), with 93% (median) of distal LAD cross sections being normal compared with 21% of mid and 0% of proximal cross sections (P < .0001). Right coronary artery plaque gradient was less pronounced vs the LAD; plaque burden was 37% ± 13% in proximal, 40% ± 10% in mid, and 36% ± 10% in distal RCA, followed by 31% ± 11% in PDA and 33% ± 10% in PLA. This was supported by the median percentage of normal cross sections/segment: 0% proximal, 0% mid, and 23% distal RCA sections plus 100% PDA and 48% PLA sections.Conclusions: Intravascular ultrasound data indicated a proximal-to-distal LAD plaque gradient; significant disease was uncommon in the distal LAD. Conversely, the proximal-to-distal RCA plaque gradient was less distinct than the LAD, although disease in the PDA was still reduced compared with proximal segments.

Comparison of transradial and femoral approaches for percutaneous coronary interventions: A systematic review and hierarchical Bayesian meta-analysis

2012-04-01

Background: Despite lower risks of access site–related complications with transradial approach (TRA), its clinical benefit for percutaneous coronary intervention (PCI) is uncertain. We conducted a systematic review and meta-analysis of clinical studies comparing TRA and transfemoral approach (TFA) for PCI.Methods: Randomized trials and observational studies (1993-2011) comparing TRA with TFA for PCI with reports of ischemic and bleeding outcomes were included. Crude and adjusted (for age and sex) odds ratios (OR) were estimated by a hierarchical Bayesian random-effects model with prespecified stratification for observational and randomized designs. The primary outcomes were rates of death, combined incidence of death or myocardial infarction, bleeding, and transfusions, early (≤30 days) and late after PCI.Results: We collected data from 76 studies (15 randomized, 61 observational) involving a total of 761,919 patients. Compared with TFA, TRA was associated with a 78% reduction in bleeding (OR 0.22, 95% credible interval [CrI] 0.16-0.29) and 80% in transfusions (OR 0.20, 95% CrI 0.11-0.32). These findings were consistent in both randomized and observational studies. Early after PCI, there was a 44% reduction of mortality with TRA (OR 0.56, 95% CrI 0.45-0.67), although the effect was mainly due to observational studies (OR 0.52, 95% CrI 0.40-0.63, adjusted OR 0.49 [95% CrI 0.37-0.60]), with an OR of 0.80 (95% CrI 0.49-1.23) in randomized trials.Conclusion: Our results combining observational and randomized studies show that PCI performed by TRA is associated with substantially less risks of bleeding and transfusions compared with TFA. Benefit on the incidence of death or combined death or myocardial infarction is found in observational studies but remains inconclusive in randomized trials.

Safety and efficacy of rescue angioplasty for ST-elevation myocardial infarction with high utilization rates of glycoprotein IIb/IIIa inhibitors

2012-04-01

Background: Fibrinolytic therapies remain widely used for ST-elevation myocardial infarction, and for “failed reperfusion,” rescue percutaneous coronary intervention (PCI) is guideline recommended to improve outcomes. However, these recommendations are based on data from an earlier era of pharmacotherapy and procedural techniques.Methods and Results: To determine factors affecting prognosis after rescue PCI, we studied 241 consecutive patients (median age 55 years, interquartile range [IQR] 48-65) undergoing procedures between 2001 and 2009 (53% anterior ST-elevation myocardial infarction and 78% transferred). The median treatment-related times were 1.2 hours (IQR 0.8-2.2) from symptom onset to door, 2 hours (IQR 1.3-3.2) from symptom onset to fibrinolysis (93% tenecteplase), and 3.9 hours (IQR 3.1-5.2) from fibrinolysis to balloon. Procedural characteristics were stent deployment in 95% (11.6% drug eluting) and 78% glycoprotein IIb/IIIa inhibitor use, and Thrombolysis In Myocardial Infarction (TIMI) 3 flow rates pre-PCI and post-PCI were 41% and 91%, respectively (P < .001). At 30 days, TIMI major bleeding occurred in 16 (6.6%) patients, and 23 (9.5%) patients received transfusions; nonfatal stroke occurred in 4 (1.7%) patients (2 hemorrhagic). Predictors of TIMI major bleeding were female gender (odds ratio 3.194, 95% CI 1.063-9.597; P = .039) and pre-PCI shock (odds ratio 3.619, 95% CI,1.073-12.207; P = .038). Mortality at 30 days was 6.2%, and 3.2% in patients without pre-PCI shock. One-year mortality was 8.2% (5.3% in patients without pre-PCI cardiogenic shock), 5.2% had reinfarction, and the target vessel revascularization rate was 6.4% (2.6% in arteries ≥3.5 mm in diameter). Pre-PCI shock, female gender, and post-PCI TIMI flow grades ≤2 were significant predictors of 1-year mortality on multivariable regression modeling, but TIMI major bleeding was not.Conclusions: Rescue PCI with contemporary treatments can achieve mortality rates similar to rates for contemporary primary PCI in patients without pre-PCI shock. Whether rates of bleeding can be reduced by different pharmacotherapies and interventional techniques needs clarification in future studies.

Patient-focused intervention to improve long-term adherence to evidence-based medications: A randomized trial

2012-04-01

Background: Nonadherence to cardiovascular medications is a significant public health problem. This randomized study evaluated the effect on medication adherence of linking hospital and community pharmacists.Methods: Hospitalized patients with coronary artery disease discharged on aspirin, β-blocker, and statin who used a participating pharmacy were randomized to usual care or intervention. The usual care group received discharge counseling and a letter to the community physician; the intervention group received enhanced in-hospital counseling, attention to adherence barriers, communication of discharge medications to community pharmacists and physicians, and ongoing assessment of adherence by community pharmacists. The primary end point was self-reported use of aspirin, β-blocker, and statin at 6 months postdischarge; the secondary end point was a ≥75% proportion of days covered (PDC) for β-blocker and statin through 6 months postdischarge.Results: Of 143 enrolled patients, 108 (76%) completed 6-month follow-up, and 115 (80%) had 6-month refill records. There was no difference between intervention and control groups in self-reported adherence (91% vs 94%, respectively, P = .50). Using the PDC to determine adherence to β-blockers and statins, there was better adherence in the intervention versus control arm, but the difference was not statistically significant (53% vs 38%, respectively, P = .11). Adherence to β-blockers was statistically significantly better in intervention versus control (71% vs 49%, respectively, P = .03). Of 85 patients who self-reported adherence and had refill records, only 42 (49%) were also adherent by PDC.Conclusions: The trend toward better adherence by refill records with the intervention should encourage further investigation of engaging pharmacists to improve continuity of care.

Exercise intervention and inflammatory markers in coronary artery disease: A meta-analysis

2012-04-01

Background: Inflammatory activity plays a role in the development and progression of coronary artery disease (CAD), and exercise confers survival benefit. We performed a meta-analysis of changes in inflammatory biomarkers over the course of exercise interventions in patients with CAD.Methods: We searched MEDLINE, Embase, the Cochrane Collaboration, AMED, and CINAHL for studies reporting peripheral inflammatory biomarker concentrations before and after exercise interventions of ≥2 weeks in patients with CAD. Data were summarized using standard mean differences (SMD) and 95% CIs.Results: Twenty-three studies were included. Concentrations of C-reactive protein (CRP; SMD −0.345, 95% CI −0.444 to −0.246, n = 1,466, P < .001), interleukin 6 (SMD −0.546, 95% CI −0.739 to −0.353, n = 280, P < .001), fibrinogen (SMD −0.638, 95% CI −0.953 to −0.323, n = 247, P < .001), and vascular cell adhesion molecule 1 (SMD −0.413, 95% CI −0.778 to −0.048, n = 187, P = .027) were lower postintervention. Higher total cholesterol (B = −0.328, 95% CI −0.612 to −0.043, P = .026) and higher total/high-density lipoprotein cholesterol ratios (B = −0.250, 95% CI −0.425 to −0.076, P = .008) at baseline were associated with greater reductions in CRP. In controlled studies, follow-up concentrations of CRP (SMD −0.500, 95% CI −0.844 to −0.157, nexercise/control = 485/284, P = .004), and fibrinogen (SMD −0.544, 95% CI −1.058 to −0.030, nexercise/control = 148/100, P = .038) were lower in subjects who exercised compared with controls.Conclusion: Exercise training is associated with reduced inflammatory activity in patients with CAD. C-reactive protein and fibrinogen have provided the strongest evidence. Higher baseline CRP and adverse baseline lipid profiles predicted greater reductions in CRP.

The relationship between perceived discrimination and coronary artery obstruction

Brian J. Ayotte, Leslie R.M. Hausmann, Jeff Whittle, Nancy R. Kressin — 2012-04-01

Background: Chronic stressors such as perceived discrimination might underlie race disparities in cardiovascular disease. This study focused on the relationship between perceived discrimination and risk of severe coronary obstruction while also accounting for multiple psychosocial variables and clinical factors.Methods: Data from 793 (629 white and 164 black) male veterans with positive nuclear imaging studies were analyzed. Participants were categorized as being at low/moderate or high risk for severe coronary obstruction based on results of their nuclear imaging studies. Hierarchical logistic regression models were tested separately for blacks and whites. The first step of the models included clinical factors. The second step included the psychosocial variables of optimism, religiosity, negative affect, and social support. The final step included perceived discrimination.Results: Perceived discrimination was positively related to risk of severe obstruction among blacks but not among whites after controlling for clinical and psychosocial variables. Similar results were found in patients who underwent coronary angiography (n = 311).Conclusions: Perceived discrimination was associated with risk of severe coronary obstruction among black male veterans and could be an important target for future interventions.

Accuracy of intracardiac echocardiography for aortic root assessment in patients undergoing transcatheter aortic valve implantation

2012-04-01

Background: Multislice computed tomography (MSCT) has generally been accepted as the most accurate modality fulfilling this purpose with good reproducibility. A major drawback of MSCT consists in the use of contrast dye, which may be unsafe in transcatheter aortic valve implantation (TAVI) patients who frequently are affected by renal failure. We sought to appraise the accuracy of intracardiac echocardiography (ICE) in measurements of structures in the aortic root in patients undergoing TAVI.Methods: Aortic annulus and sinus of Valsalva diameters were measured using ICE, performed during standard invasive preprocedural assessment in 30 consecutive patients with severe aortic stenosis referred for TAVI. Multislice computed tomography was performed in all patients afterward, and aortic root measurements were made by an independent radiologist.Results: Effective ICE measurements were obtained in all patients, easily and without any complication. Mean aortic annulus diameters were 21.9 ± 1.8 mm using ICE, 22.0 ± 1.9 mm using MSCT (3-chamber [3-C] view) and 22.8 ± 1.8 mm using the mean of long-axis and short-axis (L-ax/S-ax) view MSCT (P = .192, ICE vs 3-C MSCT; P < .001, ICE vs L-ax/S-ax MSCT, respectively). Correlation between ICE and both MSCT measurements was good (r2 = 0.83, P < .001; r2 = 0.80, P < .001, respectively). Mean sinus of Valsalva diameters were 32.3 ± 3.3 mm using ICE and 32.5 ± 3.1 mm using 3-C MSCT view (P = .141). Even in this case, correlation between ICE and both MSCT measurements was excellent (r2 = 0.96, P < .001).Conclusions: In patients referred for TAVI, measurements of the aortic annulus and the sinus of Valsalva using ICE compare favorably with those made at MSCT. This approach might be a useful and reproducible strategy in patients with severe renal impairment to avoid the administration of contrast dye during MSCT.

Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study

2012-04-01

Background: Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS).Methods: Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1:1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events.Results: During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03).Conclusions: Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis.

Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy: Rationale, initial results, and advantages

2012-04-01

Background: A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were to establish the long-term predictive value of an LBBB-related strain pattern and to identify changes in contraction patterns during short-term and long-term CRT.Methods and Results: Sixty-seven patients with standard CRT criteria were prospectively enrolled between early 2009 and late 2010. Echocardiography including regional strain analysis by 2-dimensional speckle tracking was performed 1 week before implantation, at day 1, and 6 months after. Response was defined as a decrease in left ventricular end-systolic volume ≥15%. The predictive ability of a classical pattern was compared with time-to-peak measurements from velocity and deformation analysis.Forty-three patients (65%) were classified as responders. The presence of a classical pattern showed 91% specificity and 95% sensitivity for response and performed significantly better than time-to-peak parameters in prediction of response to CRT (P < .001, all). In responders, CRT acutely increased septal longitudinal peak systolic strain (−8.7% ± 3.6% to −11.1% ± 3%, P < .001) but not in nonresponders.Conclusions: The classical pattern is highly predictive of response to CRT and superior to time-to-peak methods. Patients who obtain long-term reverse remodeling are characterized by short-term reversal of the classical strain pattern. These findings emphasize the value of recognizing potentially reversible strain patterns in selection of CRT candidates.

The impact of high-density lipoprotein cholesterol levels on long-term outcomes after non–ST-elevation myocardial infarction

Danielle Duffy, DaJuanicia N. Holmes, Matthew T. Roe, Eric D. Peterson — 2012-04-01

Background: Low serum high-density lipoprotein cholesterol (HDL-C) level is a potent risk factor for developing atherosclerosis, yet it is uncertain if HDL-C level at the time of non–ST-segment elevation myocardial infarction (NSTEMI) has downstream prognostic importance.Methods: We evaluated 24,805 patients with NSTEMI aged ≥65 years enrolled at 434 Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) participating hospitals between February 15, 2003, and December 30, 2006, who had clinical data linked to Medicare files through December 31, 2008. Unadjusted and adjusted hazard ratios (HRs) were calculated to determine the association between HDL-C level at initial hospitalization and all-cause mortality, as well as a combined outcome of all-cause mortality or recurrent myocardial infarction (MI).Results: Overall, 50% of patients had low HDL-C (≤40 mg/dL) and 18% had very low HDL-C (≤30 mg/dL). The rate of all-cause mortality was 39.5% during a median follow-up of 2.9 years; death or recurrent MI occurred in 43% in this older population with NSTEMI. Compared with patients who had normal HDL-C, those with very low HDL-C had a modest but significantly higher long-term mortality risk (adjusted HR 1.12, 95% CI 1.06-1.19, P = .0001). The adjusted HR for mortality or recurrent MI was the same. When modeled as a continuous variable, every 5-mg/dL decrement in HDL-C below 40 mg/dL was associated with a 5% increased risk of long-term mortality, as well as the combined end point.Conclusions: Older patients with NSTEMI with low levels of HDL-C are at increased risk for downstream mortality or recurrent MI. Future studies are needed to evaluate strategies to reduce this residual risk.

Preventing cardiovascular disease in primary care: Role of a national risk factor management program

2012-04-01

Background: Heartwatch, a structured risk factor modification program for secondary prevention of cardiovascular (CV) disease (CVD) in primary care, is associated with improvements in CV risk factors in participating patients. However, it is not known whether Heartwatch translates into reductions in clinically important CV events.Objective: The aim of the study was to determine the association between participation in Heartwatch and future risk of CV events in patients with CVD.Methods: The study consisted of a prospective cohort of 1,609 patients with CVD in primary care practices. Of these, 97.5% had data available on Heartwatch participation status, of whom 15.2% were Heartwatch participants. Cox proportional hazards models were used to determine the association between Heartwatch participation and risk of the CV composite (CV death, nonfatal myocardial infarction, heart failure, and nonfatal stroke). All-cause mortality and CV mortality were secondary outcome measures.Results: During follow-up, the CV composite occurred in 208 patients (13.6%). Of Heartwatch participants, 8.4% experienced the CV composite compared with 14.5% of nonparticipants (P = .003). Participation in Heartwatch was associated with a significantly reduced risk of the CV composite (hazard ratio [HR] 0.52, 95% CI, 0.31-0.87), CV mortality (HR 0.31, 95% CI, 0.11-0.89), and all-cause mortality (HR 0.32, 95% CI, 0.15-0.68). Heartwatch participation was also associated with greater reductions in mean systolic blood pressure (P = .047), mean diastolic blood pressure (P < .001), and greater use of secondary preventative therapies for CVD, such as lipid-lowering agents (P < .001), β-blockers (P < .001), and angiotensin-converting enzyme inhibitors (P < .001).Conclusion: Heartwatch is associated with a reduced risk of major vascular events and improved risk factor modification, supporting its potential as a nationwide program for secondary prevention of CVD.

Safety and effectiveness of antithrombotic strategies in older adult patients with atrial fibrillation and non–ST elevation myocardial infarction

2012-03-14

Background: We aimed to study the comparative safety and effectiveness of various antithrombotic treatment strategies among older adults with non–ST elevation myocardial infarction (NSTEMI) and atrial fibrillation (AF).Methods: Using the CRUSADE registry linked to longitudinal Medicare claims data, we examined NSTEMI patients aged ≥65 years with a concomitant diagnosis of AF. Multivariable Cox analysis was used to compare risk of rehospitalization for bleeding and a major cardiac composite end point of death, readmission for myocardial infarction, or stroke, according to discharge antithrombotic strategy.Results: Among 7619 NSTEMI patients with AF, 29% were discharged on aspirin alone; 37%, on aspirin + clopidogrel; 7%, on warfarin alone; 17%, on aspirin + warfarin; and 10%, on warfarin + aspirin + clopidogrel. There was no difference in predicted stroke risk between groups. By 1 year, 12.2% of patients were rehospitalized for bleeding, and 33.1% had a major cardiac event. Relative to aspirin alone, antithrombotic intensification was associated with increased bleeding risk (aspirin + clopidogrel adjusted HR 1.22, 95% CI 1.03-1.46 and warfarin + aspirin HR 1.46, 95% CI 1.21-1.80). Patients treated with aspirin + clopidogrel + warfarin had the highest observed bleeding risk (HR 1.65, 95% CI 1.30-2.10). One-year risk of the major cardiac end point was similar between groups, although, relative to aspirin only, there was a trend toward lower risk for the warfarin + aspirin group (HR 0.88, 95% CI 0.78-1.00).Conclusions: Older NSTEMI patients with AF are at high risk for subsequent bleeding and major cardiac events. Increased antithrombotic management was associated with increased bleeding risk. Further investigation is needed to clarify whether these risks are counterbalanced by reduced thromboembolic events in this population.

Age of natural menopause and atrial fibrillation: The Framingham Heart Study

2012-03-30

Background: Early menopausal age is associated with risk of cardiovascular events including myocardial infraction, stroke, and increased mortality. Relations between menopausal age and atrial fibrillation (AF) have not been investigated. We examined the association between menopausal age and AF.Methods: Framingham Heart Study women ≥60 years old without prevalent AF and natural menopause were followed up for 10 years or until incident AF. Menopausal age was modeled as a continuous variable and by categories (<45, 45-53, and >53 years). We used Cox proportional hazards regression to determine associations between menopausal age and AF risk.Results: In 1,809 Framingham women (2,662 person-examinations, mean baseline age 71.4 ± 7.6 years, menopausal age 49.8 ± 3.6 years), there were 273 unique participants with incident AF. We did not identify a significant association between the SD of menopausal age (3.6 years) and AF (hazard ratio [HR] per SD 0.94, 95% CI 0.83-1.06; P = .29). In a multivariable model with established risk factors for AF, menopausal age was not associated with incident AF (HR per SD 0.97, 95% CI 0.86-1.09; P = .60). Examining categorical menopausal age, earlier menopausal age (<45 years) was not significantly associated with increased AF risk compared with older menopausal age >53 years (HR 1.20, 95% CI 0.74-1.94; P = .52) or menopausal age 45 to 53 years (HR 1.38, 95% CI 0.93-2.04; P = .11).Conclusion: In our moderate-sized, community-based sample, we did not identify menopausal age as significantly increasing AF risk. However, future larger studies will need to examine whether there is a small effect of menopausal age on AF risk.

Relationship of antihypertensive treatment to plasma markers of vascular inflammation and remodeling in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis study

2012-04-01

Background: Antihypertensive agents lower the risk of cardiovascular events, but whether they affect pathways important in inflammation and plaque remodeling in atherosclerosis is uncertain. We assessed whether 2 commonly used antihypertensive agents affected plasma biomarkers reflecting specific inflammatory and remodeling processes over 2 years in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study.Methods: The study was a randomized controlled trial of 2 antihypertensives (amlodipine and enalapril) compared with placebo in patients with coronary artery disease and diastolic blood pressure less than 100 mm Hg. In 196 subjects who had baseline and 2-year intravascular coronary ultrasound examinations, we measured plasma interleukin 18, interleukin 1 receptor antagonist, matrix metalloproteinase 9, neopterin, and C-reactive protein. Results for both treatment groups were pooled and compared with placebo.Results: Antihypertensive treatment with either agent significantly lowered diastolic blood pressure (−4.7 vs placebo 1.3 mm Hg, P = .002) and progression of coronary atheroma (Δ percent atheroma volume 0.6 vs placebo 2.1, P = .031). Antihypertensive therapy did not affect plasma biomarkers of inflammation or plaque remodeling in the 135 subjects with baseline and 2-year biomarker samples. Progression in percent atheroma volume was significantly less in subjects taking statins at baseline (−2.5%, P = .0008).Conclusions: In patients with coronary artery disease and well-controlled risk factors, antihypertensive therapy lowered blood pressure and progression of coronary atherosclerosis but did not affect plasma biomarkers of inflammation and remodeling. Antihypertensives may decrease atheroma progression by mechanisms other than those reflected by these plasma biomarkers.

Regarding the impact of left ventricular size on response to cardiac resynchronization therapy

Gaetano Santulli, Salvatore D'Ascia, Cristofaro D'Ascia — 2012-04-01

We read with interest the report by Rickard et al in a recent issue of the journal regarding the impact of left ventricular size on response to cardiac resynchronization therapy (CRT).

Cognitive decline and ischemic microlesions after coronary catheterization: A comparison to coronary artery bypass

Todd K. Rosengart — 2012-04-01

We read with great interest the report by Schwarz et al titled, “Cognitive decline and ischemic microlesions after coronary catheterization: a comparison to coronary artery bypass grafting,” We congratulate the authors on a well-conducted study, but we must point out some very concerning deficiencies in their reported conduct of coronary artery bypass grafting (CABG) procedures. As clearly noted in our prior study, this attention to detail can have significant implications in terms of the cognitive risk of CABG patients, presumably reflective of an increased incidence of cerebral emboli as a result of these deficiencies. Specifically, the Giessen and Bad Nauheim groups failed to perform epiaortic echocardiography to identify and avoid aortic plaques, failed to use a right angle or diffusing aortic cannula, and failed to use a “single clamp” technique for performing their proximal anastamoses. Each of these steps can add significantly to the incidence of cerebral microemboli, which the authors clearly identify as a source of “postinterventional cognitive dysfunction.” Although the authors are to be congratulated on a well-conducted neuropsychological study, we would caution that it is imperative that open heart procedures be conducted with “full cognitive protection” to best serve their patients. At a minimum, it is important that we do not extrapolate to the general CABG population the results of such studies that do not use these protections.

A need, also, for transformative innovation in the definition of hypertension

Oscar M.P. Jolobe — 2012-04-01

The recognition that “hypertension is a silent disease with few or no symptoms until the onset of long-term complications” should prompt a reappraisal of the level of blood pressure (BP) considered to be consistent with the definition of hypertension. In the era when a BP of 140/90 mm Hg or more was the defining feature of hypertension, the latter was characterized as “a rise in blood pressure…that increases the risk of cerebral, cardiac, and renal events.” Nevertheless, notwithstanding the documentation that the risk of cardiovascular disease is higher in subjects aged 35 to 64 years with systolic BP in the range of 130 to 139 mm Hg and/or diastolic BP of 85 to 89 mm Hg than in counterparts with systolic BP <120 mm Hg and diastolic BP <80 mm Hg, the logical next step has not been taken to redefine hypertension in the light of these findings. Redefinition of hypertension as a systolic BP of 130 mm Hg or more and/or a diastolic BP of 85 mm Hg or more would have an especially powerful impact on the cardiovascular health of women, given the fact that, in the above study, the risk factor–adjusted ratio for cardiovascular disease reached a higher level, namely, 2.5 (95% CI 1.6-4.1), in women than in men, for whom the corresponding ratio was 1.6 (95% CI 1.1-2.2). Hence, as to mitigate the risk of hypertension-related target organ damage, there should be a corresponding transformative redefinition of goal BP, exemplified by the study where tight control of systolic BP to a target level of <130 mm Hg was associated, on 2-year follow-up, with significantly (P = .008) lower prevalence of left ventricular hypertrophy and significantly (P = .044) lower prevalence of new-onset atrial fibrillation than the control of systolic BP to the more lenient target level of <140 mm Hg.

Authors' response to “A need, also, for transformative innovation in the definition of hypertension”

Robin Roark, Bimal R. Shah, Eric D. Peterson — 2012-04-01

We appreciate the comments regarding the need for redefining optimal blood pressure (BP) targets and agree with you that a redefinition of hypertension (HTN) could impact hypertensive patients' longitudinal outcomes. Although we acknowledge that there are epidemiologic data demonstrating that individuals with lower BP levels have better outcomes, we also note that there are limited and conflicting data on whether medical intervention for “pre-hypertension” or more aggressive therapeutic BP control will improve patient outcomes. As such, we concentrated on current guideline-recommended thresholds to define HTN. Our goal in the study was to highlight that better systems are needed to recognize, treat, and monitor the impact of HTN. Even with current definitions of high BP, 30% to 50% of adults in the United States are not at their BP goal. As a result, we feel that redefining BP thresholds for HTN alone will not improve outcomes without simultaneously improving our care and payment systems to support reaching these goals.

Could radial instead of femoral access for coronary angiography change renal outcome? Nephrologists call for help

Piero Stratta, Cristina Bozzola, Marco Quaglia — 2012-04-01

Rarely does one have an opportunity to share an interdisciplinary project such as following the stimulating article recently published concerning design and rationale of a randomized comparison of radial versus femoral access for coronary angiography/intervention in patients with acute coronary syndromes.

Authors' reply to “Could radial instead of femoral access for coronary angiography change renal outcome? Nephrologists call for help”

Sanjit S. Jolly, John Cairns, Shamir R. Mehta — 2012-04-01

Stratta suggests that radial instead of femoral access for coronary angiography may potentially reduce the incidence of acute kidney injury after cardiac catheterization. They suggest that, by avoiding passing through the descending aorta with radial instead of femoral access, one may reduce the incidence of atheroemboli to the renal arteries. They point out that, in a large observational study, radial compared with femoral access was associated with less acute kidney injury after adjustment for baseline variables. However, because of unmeasured confounders, selection bias could account for the differences observed in this observational study.

The not so “ideal” body weight–based dosing of Integrilin in obesity

Manjunath P. Pai, Anne N. Nafziger, Joseph S. Bertino — 2012-03-13

Vavalle et al recently compared end of infusion concentrations of Integrilin (eptifibatide) in obese patients (129-156 kg) scheduled to undergo elective percutaneous interventions. Their study objective was to compare actual body weight dosing (ABW), ideal body weight (IBW) dosing, and standard dosing of eptifibatide (based on the current product label). The authors speculated that ABW- or IBW-based dosing approaches might be better than standard dosing in patients weighing >121 kg. However, the underlying study presumption that IBW-based dosing might be better than standard dosing is flawed and may have contributed to the adverse outcomes seen in this study.

Authors' reply to “The not so ‘ideal’ body weight–based dosing of Integrilin in obesity”

John P. Vavalle, John H. Alexander — 2012-03-13

We appreciate the comments of Pai et al regarding the ideal body weight (IBW) eptifibatide dosing strategy investigated in obese patients undergoing percutaneous coronary intervention in the KILO study. KILO was initially designed to compare standard eptifibatide dosing with an actual body weight (ABW) dosing strategy using previously defined pharmacokinetic and pharmacodynamic targets for eptifibatide serum concentration and platelet inhibition. Because obese patients have increased body weight because of a disproportionate increase in extravascular adipose tissue and because eptifibatide distributes predominantly into the intravascular space, we felt that an ABW-based dosing strategy might lead to overdosing of eptifibatide. We, therefore, chose to include an arm in the study that used IBW, testing the hypothesis that IBW may be more proportional to intravascular volume than ABW. Indeed, as illustrated in Figure 1, the IBW dosing arm in KILO had the most consistent (flattest) plasma concentrations across patient weights, although, as Pai et al point out, at a concentration substantially lower than either the standard or ABW dosing regimens. The ideal dosing regimen for eptifibatide might, therefore, be some larger dose per kilogram dose administered according to an IBW. Overall, we agree with Pai et al that the tailoring of drug dosing using pharmacokinetic and pharmacodynamic approaches is important and might be particularly important in the growing obese population.

Improvement in ejection fraction—but do not forget the basics, the medications

Vijaiganesh Nagarajan — 2012-04-01

I read the article by Wilcox et al with great interest. In this article, approximately 28.6% of patients had >10% improvement in left ventricular ejection fraction (EF) during 24-month follow-up. Absence of ischemic heart disease or myocardial infarction was the clinically significant predictor of improvement in EF in this study. Interestingly, neither revascularization nor cardiovascular drugs were associated with improvement in EF. However, multiple studies have shown that cardiovascular drugs such as β-blockers (BB), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARB) are associated with improvement in EF. Ejection fraction is known to be one of the better predictors of mortality. Wilcox et al explained the absence of correlation between EF and these medications by the fact that >80% of patients were already on BB, ACEI, or ARB at the time of first EF assessment. The aforementioned classes of medications were not only shown to improve EF but also have got significant mortality benefit. As this study reaffirms the positive approach to be shown to patients with systolic heart failure, we recommend clinicians to be more aggressive in using cardiovascular medications with mortality benefit in patients with systolic heart failure when indicated. So with all the new trials every day, please do not forget the basics—the importance of BB, ACEI, and ARB cannot be reemphasized more.

In response to Nagarajan's letter to the editor “Improvement in ejection fraction—but do not forget the basics, the medications”

Jane E. Wilcox, Clyde W. Yancy, Mihai Gheorghiade, Gregg C. Fonarow — 2012-04-01

The comments from Dr Nagarajan regarding our article are greatly appreciated. We fully agree that evidence-based, guideline-directed medication and device therapies are essential for improving left ventricular ejection fraction (LVEF) and clinical outcomes and remain the cornerstone of therapy in patients with heart failure (HF) with reduced LVEF. We have previously reported that use of these evidence-based medications and device therapies for HF was associated with substantial improvements in 24-month survival. The salient point of the present study is that the diagnosis of HF is not always a fait accompli, but rather a dynamic process from which real recovery is possible with current available therapies. In this prospective cohort, almost one third of patients with HF had a substantial (92% relative improvement) increase in LVEF, a heretofore not fully characterized phenomenon, which may be partly related to the myocardial substrate. These improvements occurred in a background of high baseline rates of HF medications therapies and additional improvements that result from a fully deployed performance improvement process as orchestrated in the IMPROVE HF study. Identifying clinical predictors of recovery remains challenging given the heterogeneity of the HF population. Although we were able to identify certain clinical characteristics independently associated with LVEF improvement, there are likely additional factors that are important. Nevertheless, our data demonstrate that many patients with well-established HF may be candidates for substantial recovery of ventricular function and, in turn, much improved outcomes. Going forward, viable but dysfunctional myocardium that is potentially recoverable sets the stage for further research and may be an important target for future therapies.

2012-04-01

Editorial Board

2012-04-01

Information for Readers

2012-04-01

American Heart Journal

Triple antithrombotic therapy after coronary stenting in the elderly with atrial fibrillation: Necessary or too hazardous?

Rationale and design of a Global Rheumatic Heart Disease Registry: The REMEDY study

Target temperature management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design

Design and rationale for the PREVAIL study: Effect of e-Health individually tailored encouragements to physical exercise on aerobic fitness among adolescents with congenital heart disease—a randomized clinical trial

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): Rationale and study design of a randomized multicenter trial in a Dutch all-comers population

Reinfarction after percutaneous coronary intervention or medical management using the universal definition in patients with total occlusion after myocardial infarction: Results from long-term follow-up of the Occluded Artery Trial (OAT) cohort

Differences in symptom presentation and hospital mortality according to type of acute myocardial infarction

Heart rate recovery in pulmonary arterial hypertension: Relationship with exercise capacity and prognosis

Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension

Use of a highly sensitive assay for cardiac troponin T and N-terminal pro-brain natriuretic peptide to diagnose acute rejection in pediatric cardiac transplant recipients

ComparisOn of neointimal coVerage betwEen zotaRolimus-eluting stent and everolimus-eluting stent using Optical Coherence Tomography (COVER OCT)

Effect of strut thickness on neointimal atherosclerotic change over an extended follow-up period (≥4 years) after bare-metal stent implantation: Intracoronary optical coherence tomography examination

Use and overuse of left ventriculography

An intravascular ultrasound appraisal of atherosclerotic plaque distribution in diseased coronary arteries

Comparison of transradial and femoral approaches for percutaneous coronary interventions: A systematic review and hierarchical Bayesian meta-analysis

Safety and efficacy of rescue angioplasty for ST-elevation myocardial infarction with high utilization rates of glycoprotein IIb/IIIa inhibitors

Patient-focused intervention to improve long-term adherence to evidence-based medications: A randomized trial

Exercise intervention and inflammatory markers in coronary artery disease: A meta-analysis

The relationship between perceived discrimination and coronary artery obstruction

Accuracy of intracardiac echocardiography for aortic root assessment in patients undergoing transcatheter aortic valve implantation

Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study

Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy: Rationale, initial results, and advantages

The impact of high-density lipoprotein cholesterol levels on long-term outcomes after non–ST-elevation myocardial infarction

Preventing cardiovascular disease in primary care: Role of a national risk factor management program

Safety and effectiveness of antithrombotic strategies in older adult patients with atrial fibrillation and non–ST elevation myocardial infarction

Age of natural menopause and atrial fibrillation: The Framingham Heart Study

Relationship of antihypertensive treatment to plasma markers of vascular inflammation and remodeling in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis study

Regarding the impact of left ventricular size on response to cardiac resynchronization therapy

Cognitive decline and ischemic microlesions after coronary catheterization: A comparison to coronary artery bypass

A need, also, for transformative innovation in the definition of hypertension

Authors' response to “A need, also, for transformative innovation in the definition of hypertension”

Could radial instead of femoral access for coronary angiography change renal outcome? Nephrologists call for help

Authors' reply to “Could radial instead of femoral access for coronary angiography change renal outcome? Nephrologists call for help”

The not so “ideal” body weight–based dosing of Integrilin in obesity

Authors' reply to “The not so ‘ideal’ body weight–based dosing of Integrilin in obesity”

Improvement in ejection fraction—but do not forget the basics, the medications

In response to Nagarajan's letter to the editor “Improvement in ejection fraction—but do not forget the basics, the medications”

Table of Contents

Editorial Board

Information for Readers