Bindu Kalesan

Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism

BACKGROUND The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy. METHODS We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population. RESULTS The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56). CONCLUSIONS Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT00166257.).

Very Late Coronary Stent Thrombosis of a Newer-Generation Everolimus-Eluting Stent Compared With Early-Generation Drug-Eluting Stents A Prospective Cohort Study

Background— Early-generation drug-eluting stents releasing sirolimus (SES) or paclitaxel (PES) are associated with increased risk of very late stent thrombosis occurring >1 year after stent implantation. It is unknown whether the risk of very late stent thrombosis persists with newer-generation everolimus-eluting stents (EES). Methods and Results— We assessed the risk of stent thrombosis in a cohort of 12 339 patients with unrestricted use of drug-eluting stents (3819 SES, 4308 PES, 4212 EES). Results are incidence rates per 100 person-years after inverse probability of treatment weighting to adjust for group differences. During follow-up of up to 4 years, the overall incidence rate of definite stent thrombosis was lower with EES (1.4 per 100 person-years) compared with SES (2.9; hazard ratio, 0.41; 95% confidence interval, 0.27–0.62; P<0.0001) and PES (4.4; hazard ratio, 0.33; 95% confidence interval, 0.23–0.48; P<0.0001). The incidence rate per 100 person-years of early (0–30 days), late (31 days–1 year), and very late stent thrombosis amounted to 0.6, 0.1, and 0.6 among EES-treated patients; 1.0, 0.3, and 1.6 among SES-treated patients; and 1.3, 0.7, and 2.4 among PES-treated patients. Differences in favor of EES were most pronounced beyond 1 year, with a hazard ratio of 0.33 (EES versus SES; P=0.006) and 0.34 (EES versus PES; P<0.0001). There was a lower risk of cardiac death or myocardial with EES compared with PES (hazard ratio, 0.65; 95% confidence interval, 0.56–0.75; P<0.0001), which was directly related to the lower risk of stent thrombosis–associated events (EES versus PES: hazard ratio, 0.36; 95% confidence interval, 0.23–0.57). Conclusion— Current treatment with EES is associated with a lower risk of very late stent thrombosis compared with early-generation drug-eluting stents.

Aortic Root Dimensions Among Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

OBJECTIVES The aim of this study was to characterize aortic root dimensions of patients with aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) and to evaluate sex differences. BACKGROUND The advent of TAVR makes a precise delineation of the aortic root anatomy mandatory and requires a profound anatomic understanding. METHODS Patients planned to undergo TAVR underwent screening imaging with use of a 64-slice or dual-source electrocardiogram-gated contrast-enhanced computed tomography. Anatomic dimensions were assessed at the level of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, and ascending aorta. RESULTS The study population comprised 80 men and 97 women (age: 82 ± 6 years) with symptomatic severe aortic valve stenosis. Multislice computed tomography aortic root assessment revealed larger annular and LVOT dimensions in men than women (area annulus: 483.1 ± 75.6 mm(2) vs. 386.9 ± 58.5 mm(2), p = 0.0002; area LVOT: 478.2 ± 131.0 mm(2) vs. 374.0 ± 94.2 mm(2), p = 0.0024), whereas dimensions of the ascending aorta were comparable. Both LVOT and annulus were predominantly oval without sex differences, with a higher mean ellipticity index for the LVOT compared with the annulus (1.49 ± 0.2 vs. 1.29 ± 0.1); the ascending aorta was primarily circular (1.07 ± 0.1). Although similar in mean surface area, an area mismatch of annulus and LVOT of more than 10%, 20%, and 40% was detected in 42, 9, and 2 patients, respectively. The mean distance from annulus to the left coronary ostium was smaller than the mean distance of the right coronary ostium (14.4 ± 3.6 mm vs. 16.7 ± 3.6 mm), and distances were lower among women than men. CONCLUSIONS The aortic root has specific anatomic characteristics, which affect device design, selection, and clinical outcome in patients undergoing TAVR. Female sex is associated with smaller annular and LVOT but not aortic dimensions. The degree of ellipticity as well as a significant mismatch between annular and LVOT dimensions in selected patients deserve careful evaluation.

Predictors of Clinical Outcomes in Patients With Severe Aortic Stenosis Undergoing TAVI A Multistate Analysis

Background—Patients with severe aortic stenosis at increased surgical risk continue to experience compromised long-term survival despite successful transcatheter aortic valve implantation. We used time-related pathways in a multistate analysis to identify predictors of adverse long-term outcome in patients who underwent transcatheter aortic valve implantation. Methods and Results—In a cohort of 389 patients with a mean age of 82.4±5.8 years and a STS score of 6.8±5.3 undergoing transcatheter aortic valve implantation between 2007 and 2011, multistate analysis was used to estimate mortality and stroke taking into account intercurrent events including kidney injury and the composite of access site and bleeding complications (ABC). Transapical access emerged as a predictor of kidney injury (hazard ratio [HR], 2.12; 95% confidence interval [CI] 1.00–4.47) and ABC (HR, 1.78; 95% CI, 1.07–2.96), but had no impact on the risk of stroke or death. Body mass index ⩽20 kg/m2 increased the risk of stroke or death (HR, 2.64; 95% CI, 1.25–5.54). Age >80 years (HR, 3.15; 95% CI, 1.11–8.92), body mass index ⩽20 kg/m2 (HR, 4.11; 95% CI, 1.33–12.70), prior stroke (HR, 16.42; 95% CI, 3.63–74.21), and presence of atrial fibrillation at baseline (HR, 4.12; 95% CI, 1.87–9.97) increased the risk of stroke and death after an intercurrent event of ABC. Conclusions—A body mass index ⩽20 kg/m2 was identified as a primary predictor of stroke and death after transcatheter aortic valve implantation during long-term follow-up, whereas transapical access emerged as a predictor of kidney injury and ABC. Age >80 years, body mass index ⩽20 kg/m2, prior stroke, and presence of atrial fibrillation at baseline increased the risk of stroke and death after an intercurrent event of ABC.

The Impact of Anemia on Long-Term Clinical Outcome in Patients Undergoing Revascularization With the Unrestricted Use of Drug-Eluting Stents

Background— Anemia is frequent among patients with cardiovascular disease and adversely affects prognosis. The objective of this analysis was to assess the impact of anemia on long-term clinical outcomes among patients undergoing percutaneous coronary intervention (PCI) with the unrestricted use of drug-eluting stents (DES). Methods and Results— Between April 2002 to March 2009, 6528 consecutive patients underwent PCI with the unrestricted use of DES. Among patients with anemia according to the criteria by the World Health Organization (WHO) (hemoglobin <130 g/L for men and <120 g/L for women, respectively) patients below the 25th percentile separately for men and women were defined to have severe anemia. We compared clinical outcomes among patients with severe anemia and no/mild anemia during long-term follow-up through 4 years. Whereas 21.6% of patients were found to have anemia according to the WHO definition, 347 patients (5.5%) had severe anemia (mean hemoglobin, 98±11 g/L). Severe anemia was more prevalent among the elderly (P<0.001), diabetics (P<0.001), and patients with chronic kidney disease (P<0.001). In adjusted analyses, severe anemia was associated with an increased risk of death (hazard ratio, 1.86; 95% confidence interval, 1.37–2.52; P<0.0001), cardiac death (hazard ratio, 2.32; 95% confidence interval, 1.57–3.43; P<0.0001), and myocardial infarction (hazard ratio, 2.02; 95% confidence interval, 1.36–3.01; P=0.00054) as compared with no/mild anemia without significant interaction across sexes (P=0.86) and acute coronary syndromes (P=0.61) and a trend toward a particularly high risk of mortality among anemic patients <65 years of age (P=0.07). Severe anemia resulted in a greater risk of overall definite stent thrombosis (hazard ratio, 2.59; 95% confidence interval, 1.48–4.54; P=0.00089). Conclusions— Severe anemia is common among patients undergoing PCI with the unrestricted use of DES and adversely affects long-term prognosis, including survival.

Firearm legislation and firearm mortality in the USA: a cross-sectional, state-level study

BACKGROUND In an effort to reduce firearm mortality rates in the USA, US states have enacted a range of firearm laws to either strengthen or deregulate the existing main federal gun control law, the Brady Law. We set out to determine the independent association of different firearm laws with overall firearm mortality, homicide firearm mortality, and suicide firearm mortality across all US states. We also projected the potential reduction of firearm mortality if the three most strongly associated firearm laws were enacted at the federal level. METHODS We constructed a cross-sectional, state-level dataset from Nov 1, 2014, to May 15, 2015, using counts of firearm-related deaths in each US state for the years 2008-10 (stratified by intent [homicide and suicide]) from the US Centers for Disease Control and Preventions Web-based Injury Statistics Query and Reporting System, data about 25 firearm state laws implemented in 2009, and state-specific characteristics such as firearm ownership for 2013, firearm export rates, and non-firearm homicide rates for 2009, and unemployment rates for 2010. Our primary outcome measure was overall firearm-related mortality per 100,000 people in the USA in 2010. We used Poisson regression with robust variances to derive incidence rate ratios (IRRs) and 95% CIs. FINDINGS 31,672 firearm-related deaths occurred in 2010 in the USA (10·1 per 100,000 people; mean state-specific count 631·5 [SD 629·1]). Of 25 firearm laws, nine were associated with reduced firearm mortality, nine were associated with increased firearm mortality, and seven had an inconclusive association. After adjustment for relevant covariates, the three state laws most strongly associated with reduced overall firearm mortality were universal background checks for firearm purchase (multivariable IRR 0·39 [95% CI 0·23-0·67]; p=0·001), ammunition background checks (0·18 [0·09-0·36]; p<0·0001), and identification requirement for firearms (0·16 [0·09-0·29]; p<0·0001). Projected federal-level implementation of universal background checks for firearm purchase could reduce national firearm mortality from 10·35 to 4·46 deaths per 100,000 people, background checks for ammunition purchase could reduce it to 1·99 per 100,000, and firearm identification to 1·81 per 100,000. INTERPRETATION Very few of the existing state-specific firearm laws are associated with reduced firearm mortality, and this evidence underscores the importance of focusing on relevant and effective firearms legislation. Implementation of universal background checks for the purchase of firearms or ammunition, and firearm identification nationally could substantially reduce firearm mortality in the USA. FUNDING None.

Firearm-related Hospitalizations and In-Hospital Mortality in the United States, 2000–2010

Most firearm-related injuries are nonfatal and require hospitalization. Using data on 3,257,720 hospitalizations from the National Hospital Discharge Survey (2000-2010), we determined overall and cause-, gender-, and race-specific trends in firearm-related hospitalization (FRH) and determinants of in-hospital firearm mortality. Types of FRH evaluated, according to International Classification of Diseases, Ninth Revision, Clinical Modification, E-diagnostic codes, were accident (codes E922.0-E922.3, E922.8, and E922.9), assault (codes E965.0-E965.4), attempted suicide (codes E955.0-E955.4), legal intervention (code E970), undetermined intent (codes E985.0-E985.3), and war (code E991). A moderate reduction in FRH rates was observed from 2000 to 2011: from 62 FRHs per 100,000 hospitalizations to 57 per 100,000 (P-trend = 0.0016). The majority of FRHs were due to assault (P-trend = 0.19) or accident (P-trend = 0.32) and showed no significant reduction in rates over time, whereas rates for 14% of all FRHs-those due to attempted suicide (P-trend = 0.002) and undetermined intent (P-trend = 0.0029)-declined moderately. Moderate declines were observed among both blacks (from 213.1 FRHs per 100,000 hospitalizations to 164.4 per 100,000; P-trend = 0.049) and whites (from 38.4 FRHs per 100,000 hospitalizations to 32.2 per 100,000; P-trend = 0.031). The decline was significant only among men (effect size = 0.9, P-trend = 0.004). In conclusion, the reduction in FRH was driven by a reduction in self-inflicted and undetermined injuries. FRH rates were 6-fold greater among blacks than among whites and 14-fold greater in men than in women throughout the period.

Impact of atrial fibrillation on clinical outcomes among patients with coronary artery disease undergoing revascularisation with drug-eluting stents

AIMS Coronary artery disease (CAD) and atrial fibrillation (AF) are major determinants of morbidity and mortality. A combined treatment with antiplatelet agents and vitamin K antagonists limits the risk of stent thrombosis and stroke while increasing the rate of bleeding. The objective of this study was to investigate the impact of atrial fibrillation (AF) on long-term clinical outcomes in patients with CAD undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS Among 6,308 consecutive patients undergoing PCI with DES between 2002 and 2009, 323 (5.3%) patients were diagnosed with AF. We compared clinical outcomes between patients with and those without AF throughout four years. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), ischaemic stroke, and BARC bleeding type 3b/3c/5a/5b. In adjusted analyses, the primary composite endpoint was more frequent among patients with AF (HR 1.59, 95% CI 1.26-2.00; p<0.001). Differences were driven by an increased risk of all-cause mortality (HR 1.67, 95% CI 1.27-2.20; p=0.003), ischaemic stroke (HR 3.09, 95% CI 1.45-6.56; p=0.003), and intracranial bleeding (HR 4.28, 95% CI 1.36-13.48; p=0.013). We observed a gradient of risk among patients with higher CHA2DS2-VASc scores and modified outpatient bleeding risk index. CONCLUSIONS Among patients with CAD undergoing revascularisation with DES, AF confers an increased risk of all-cause mortality, ischaemic stroke, and intracranial bleeding. The hazard imposed by AF correlates with the CHA2DS2-VASc score.

Long-term comparison of everolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for percutaneous coronary intervention of saphenous vein grafts

AIMS Newer-generation everolimus-eluting stents (EES) have been shown to improve clinical outcomes compared with early-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in patients undergoing percutaneous coronary intervention (PCI). Whether this benefit is maintained among patients with saphenous vein graft (SVG) disease remains controversial. METHODS AND RESULTS We assessed cumulative incidence rates (CIR) per 100 patient years after inverse probability of treatment weighting to compare clinical outcomes. The pre-specified primary endpoint was the composite of cardiac death, myocardial infarction (MI), and target vessel revascularisation (TVR). Out of 12,339 consecutively treated patients, 288 patients (5.7%) underwent PCI of at least one SVG lesion with EES (n=127), SES (n=103) or PES (n=58). Up to four years, CIR of the primary endpoint were 58.7 for EES, 45.2 for SES and 45.6 for PES with similar adjusted risks between groups (EES vs. SES; HR 0.94, 95% CI: 0.55-1.60, EES vs. PES; HR 1.07, 95% CI: 0.60-1.91). Adjusted risks showed no significant differences between stent types for cardiac death, MI and TVR. CONCLUSIONS Among patients undergoing PCI for SVG lesions, newer-generation EES have similar safety and efficacy to early-generation SES and PES during long-term follow-up to four years.

Relative Contributions of Arterial Stiffness and Hypertension to Cardiovascular Disease: The Framingham Heart Study

Background The presence and implications of abnormal arterial stiffness, a potential independent predictor of outcomes, in community‐dwelling treated hypertensives is unknown. Furthermore, limited data exist regarding the risk of cardiovascular disease (CVD) associated with arterial stiffness across the entire range of blood pressure. Methods and Results We measured carotid‐femoral pulse wave velocity (PWV) and classical CVD risk factors in 2127 community‐dwelling participants (mean age 60 years, 57% women) of The Framingham Offspring Cohort. The participants were divided into 4 groups according to hypertension (yes/no, defined as blood pressure ≥140/90 mm Hg or use of antihypertensive treatment) and PWV status (high/low based on age‐ and sex‐specific median values) and followed up for CVD events (CVD death, myocardial infarction, unstable angina, heart failure, and stroke). Sixty percent (233 of 390) of controlled and 90% (232 of 258) of uncontrolled treated hypertensives had high PWV. The multivariable‐adjusted risk for CVD events (n=248, median follow‐up 12.6 years) rose from normotension with low PWV (reference) to normotension with high PWV (hazard ratio 1.29, 95% CI 0.83–2.00) and from hypertension with low PWV (hazard ratio 1.54, 95% CI 1.01–2.36) to hypertension with high PWV (hazard ratio 2.25, 95% CI 1.54–3.29). Conclusions A substantial proportion of treated hypertensives have high arterial stiffness, a finding that may explain some of the notable residual CVD risk associated with even well‐controlled hypertension. High PWV is associated with a trend towards increasing CVD risk in both nonhypertensives and hypertensives, a finding that may support the use of arterial stiffness measurements in both populations.