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Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate on the episodic associative learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show higher CRF was associated with faster learning rate. Larger hippocampal volume was also associated with faster learning rate, though hippocampal volume did not mediate the relationship between CRF and learning rate. Furthermore, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found learning rate on the EAL task was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time, we show that both higher CRF and larger hippocampal volume in healthy older adults are related to enhanced rate of relational memory acquisition.

PURPOSE: Previous studies report memory and functional connectivity of memory systems improve acutely after a single aerobic exercise session or with training, suggesting the acute effects of aerobic exercise may reflect initial changes that adapt over time. In this trial, for the first time, we test the proof-of-concept of whether the acute and training effects of aerobic exercise on working memory and brain network connectivity are related in the same participants. METHODS: Cognitively normal older participants (N=34) were enrolled in a randomized clinical trial (NCT02453178). Participants completed fMRI resting state and a face working memory N-back task acutely after light and moderate intensity exercise and after a 12-week aerobic training intervention. RESULTS: Functional connectivity did not change more after moderate compared with light intensity training. However, both training groups showed similar changes in cardiorespiratory fitness (maximal exercise oxygen uptake, VO(2)peak), limiting group-level comparisons. Acute effects of moderate intensity aerobic exercise on hippocampal-cortical connections in the default network predicted training enhancements in the same connections. Working memory also improved acutely, especially following moderate intensity, and greater acute improvements predicted greater working memory improvement with training. Exercise effects on functional connectivity of right lateralized fronto-parietal connections were related to both acute and training gains in working memory. CONCLUSION: Our data support the concept of acute aerobic exercise effects on functional brain systems and performance as an activity-evoked biomarker for exercise training benefits in the same outcomes. These findings may lead to new insights and methods for improving memory outcomes with aerobic exercise training.

Purpose In aortic stenosis patients referred for surgical and transcatheter aortic valve replacement (AVR), the evidence of diagnostic accuracy of coronary computed tomography angiography (CCTA) has been limited. The objective of this study was to investigate the diagnostic accuracy of CCTA for significant coronary artery disease (CAD) in patients referred for AVR using invasive coronary angiography (ICA) as the gold standard. Materials and methods We searched databases for all diagnostic studies of CCTA in patients referred for AVR, which reported diagnostic testing characteristics on patient-based analysis required to pool summary sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio. Significant CAD in both CCTA and ICA was defined by >50% stenosis in any coronary artery, coronary stent, or bypass graft. Results Thirteen studies evaluated 1498 patients (mean age, 74 y; 47% men; 76% transcatheter AVR). The pooled prevalence of significant stenosis determined by ICA was 43%. Hierarchical summary receiver-operating characteristic analysis demonstrated a summary area under curve of 0.96. The pooled sensitivity, specificity, and positive-likelihood and negative-likelihood ratios of CCTA in identifying significant stenosis determined by ICA were 95%, 79%, 4.48, and 0.06, respectively. In subgroup analysis, the diagnostic profiles of CCTA were comparable between surgical and transcatheter AVR. Conclusions Despite the higher prevalence of significant CAD in patients with aortic stenosis than with other valvular heart diseases, our meta-analysis has shown that CCTA has a suitable diagnostic accuracy profile as a gatekeeper test for ICA. Our study illustrates a need for further study of the potential role of CCTA in preoperative planning for AVR.

Female gender was included in stroke prediction algorithms in an attempt to improve anticoagulation rates in women with atrial fibrillation (AF). It is unclear if these efforts reduced stroke burden in women with AF. To bridge this literature gap, using the Nationwide Inpatient Sample, we assessed gender differences in the trends of hospitalizations for stroke among patients with AF in the United States in 2005 to 2014. International classification of diseases, 9th revision, clinical modification codes were used to abstract AF and stroke diagnoses. From 2005 to 2014, 18,413,291 hospitalizations of women with AF and 18,035,866 hospitalizations of men with AF were reported. Of these, 740,635 hospitalizations in women and 595,730 hospitalizations in men had stroke as the primary diagnosis. Age-adjusted stroke hospitalizations increased in women (443 per million in 2005 to 495 per million in 2014) as well as in men (351 per million in 2005 to 453 per million in 2014) (p trend 0.001). Further, anticoagulation rates increased in women (11.5% in 2005 to 24.0% in 2014) as well as in men (11.7% in 2005 to 24.9% in 2014). Stroke hospitalizations involving anticoagulated patients with AF decreased in women (411 per million in 2005 to 347 per million in 2014) as well as in men (402 per million in 2005 to 311 per million in 2014) (p trend 0.001). In conclusion, although we noted an increasing trend of stroke hospitalizations in both genders, it is reassuring to note that stroke hospitalizations involving anticoagulated patients with AF is decreasing in both genders and in particular among women.

Background Coronary artery calcium score (CACS) is a well-established test for risk stratifying asymptomatic patients for overall cardiovascular or coronary events. However; the prognostic value for incident stroke remains controversial. The objective of this study was to investigate the predictive value of CACS obtained by non-contrast electrocardiogram-gated computed tomography for incident stroke. Methods We searched PubMed, EMBASE, Cochrane databases for prospective longitudinal studies of CACS which reported the incidence of stroke. Incidence of stroke was compared in patients with and without coronary calcification. Results Three studies evaluated 13,262 asymptomatic patients (mean age=60years, 50% men) without apparent cardiovascular diseases. During a follow-up of 7.2years (median 5years, range 4.4–9.5years, 95,434patient-years), the overall pooled incidence of stroke was 0.26%/year. The pooled risk ratio of CACS>0 for incident stroke was 2.95 (95% CI: 2.18–4.01, p 2 =0%). The pooled incidence rate of stroke categorized by CACS was 0.12%/year for CACS 0, 0.26%/year for CACS 1–99, 0.41%/year for CACS 100–399 and 0.70%/year for CACS ≥400. Conclusions In asymptomatic patients without apparent cardiovascular diseases, the incidence of stroke was overall low. The presence and severity of coronary artery calcification were associated with incident stroke over mid-long term follow-up.

Aging is associated with increased carotid artery stiffness, a predictor of incident stroke, and reduced cognitive performance and brain white matter integrity (WMI) in humans. Therefore, we hypothesized that higher carotid stiffness/lower compliance would be independently associated with slower processing speed, higher working memory cost, and lower WMI in healthy middle-aged/older (MA/O) adults. Carotid β-stiffness ( P < 0.001) was greater and compliance ( P < 0.001) was lower in MA/O ( n = 32; 64.4 ± 4.3 yr) vs. young ( n = 19; 23.8 ± 2.9 yr) adults. MA/O adults demonstrated slower processing speed (27.4 ± 4.6 vs. 35.4 ± 5.0 U/60 s, P < 0.001) and higher working memory cost (−15.4 ± 0.14 vs. −2.2 ± 0.05%, P < 0.001) vs. young adults. Global WMI was lower in MA/O adults ( P < 0.001) and regionally in the frontal lobe ( P = 0.020) and genu ( P = 0.009). In the entire cohort, multiple regression analysis that included education, sex, and body mass index, carotid β-stiffness index (B = −0.53 ± 0.15 U, P = 0.001) and age group (B = −4.61 ± 1.7, P = 0.012, adjusted R2 = 0.4) predicted processing speed but not working memory cost or WMI. Among MA/O adults, higher β-stiffness (B = −0.60 ± 0.18, P = 0.002) and lower compliance (B = 0.93 ± 0.26, P = 0.002) were associated with slower processing speed but not working memory cost or WMI. These data suggest that greater carotid artery stiffness is independently and selectively associated with slower processing speed but not working memory among MA/O adults. Carotid artery stiffening may modulate reductions in processing speed earlier than working memory with healthy aging in humans. NEW & NOTEWORTHY Previously, studies investigating the relation between large elastic artery stiffness, cognition, and brain structure have focused mainly on aortic stiffness in aged individuals with cardiovascular disease risk factors and other comorbidities. This study adds to the field by demonstrating that the age-related increases in carotid artery stiffness, but not aortic stiffness, is independently and selectively associated with slower processing speed but not working memory among middle-aged/older adults with low cardiovascular disease risk factor burden.

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate in the Episodic Associative Learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show that higher CRF was associated with larger hippocampal volume and faster learning rate. Larger hippocampal volume was also associated with faster learning rate, and hippocampal volume partially mediated the relationship between CRF and learning rate. Further, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found that EAL learning rate was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time we show that higher CRF in healthy older adults is related to enhanced rate of relational memory acquisition, in part mediated by benefits on the hippocampus.

Background The 2013 American College of Cardiology/American Heart Association blood cholesterol guideline recommends high‐intensity statin therapy among certain groups of patients, but full implementation of the guideline has not yet been satisfactory. We aimed to investigate the temporal trends and predictors of high‐intensity statin therapy among veterans who had been treated with percutaneous coronary intervention ( PCI ) and followed up by cardiologists within the Veterans Health Administrative system. Methods and Results A retrospective cohort study was conducted at the Veterans Health Administrative system including all patients >18 years old who had their PCI procedure between October 2010 and September 2016. National Veterans Health Administrative databases were used to retrieve study participant's demographics, comorbid conditions, statin type and dose within 90 days before and after the PCI procedure. There were 48 862 patients who underwent a PCI procedure during the study period. High‐intensity statin use at 90 days post‐ PCI rose from 23% in 2010 to 37% before release of the 2013 American College of Cardiology/American Heart Association cholesterol guideline, then rose sharply to 80% by 2016. The projected 10‐year risk of arteriosclerotic cardiovascular disease events among our study population was projected to be ≈1841 fewer if the cohort had received high‐intensity statin therapy versus moderate‐intensity statin. Conclusions By 2016, the 2013 American College of Cardiology/American Heart Association blood cholesterol guideline was well implemented among veterans who had a PCI procedure in the Veterans Health Administrative system, suggesting systems of care can be improved to increase rates of high‐intensity statin initiation.

Radiofrequency ablation (RFA) of atrial flutter (AFL) is a commonly performed procedure with low risk of complications. Several case reports and animal studies cautioned about the risk of right coronary artery (RCA) injury following AFL ablation. This risk is due to the anatomic proximity of the RCA to the cavo-tricuspid isthmus where ablation is performed. We present a case report that demonstrates postmortem evidence of RCA injury following RFA of AFL.

AIMS Concomitant severe calcific aortic and mitral stenosis is a relatively uncommon but very challenging valvular heart disease to manage. We sought to evaluate the feasibility of a fully percutaneous approach to replace both stenotic native mitral and aortic valves using SAPIEN 3 valves. METHODS AND RESULTS An 87-year-old woman with chronic kidney disease stage 3, pul-monary hypertension, chronic obstructive pulmonary disease, a permanent pacemaker, and atrial fibrillation was referred with Class III heart failure symptoms. Her echocardiogram showed a decreased ejection fraction at 45%, severe mitral stenosis (mean gradient 13 mmHg, area 0.8 cm2) with severe MAC, and severe AS (mean gradient 35 mmHg, area 0.6 cm2). Surgical risk was felt to be very high after evaluation by our cardiothoracic sur-gery group (Society of Thoracic Surgeons risk score of 19%). She underwent simultaneous and fully percutaneous trans-femoral TAVR and transseptal TMVR using SAPIEN 3 valves. Post-implant TEE showed trace paravalvular mitral regurgitation and a mean gradient of 4 mmHg and mean aortic gradient of 8 mmHg with trace paravalvular leak. There was no LVOT obstruction. The patient was discharged seven days after the intervention. CONCLUSIONS After careful evaluation by experienced Heart Teams, combined native stenotic mitral and aortic valves can be percutaneously replaced using transcatheter SAPIEN 3 valves via transfemoral access in carefully selected high surgical risk patients.

Background Diagnostic testing in the care of patients newly presenting with symptoms suggestive of coronary artery disease may influence risk factor management, independent of test type or test results. However, little is known about changes in medications and lifestyle after anatomical or functional testing. Methods and Results We examined what factors influenced preventive medical therapy and lifestyle practices at 60 days among 10 003 symptomatic patients (53% women; mean age 61 years) randomly assigned to anatomical testing with coronary computed tomographic angiography or functional testing (NCT01174550). We also assessed the association of preventive changes with major cardiovascular events. There were no differences in medications/lifestyle at baseline. At 60 days, relative to baseline, the computed tomographic angiography strategy was associated with a higher proportion of patients newly initiating aspirin (11.8% versus 7.8%), statins (12.7% versus 6.2%), and β‐blockers (8.1% versus 5.3%), compared to functional testing ( P P =0.002) while obese/overweight status was lower ( P =0.040). Positive initial test results and revascularization demonstrated stronger associations with preventive medications and lifestyle than test type. Medication initiation was not associated with fewer cardiovascular events. Conclusions Positive initial test results and revascularization are primary drivers of changes in preventive medical and lifestyle practices, with test type making secondary contributions. However, substantial opportunities exist to further reduce cardiovascular risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01174550.

Study objective Coronary artery calcium score (CACS) is a well-established test for risk stratifying asymptomatic patients. Recent studies also indicate that CACS may accurately risk stratify stable patients presenting to the emergency department (ED) with acute chest pain; however, many were underpowered. The purpose of this systematic review and meta-analysis is to evaluate the prognostic value and accuracy of a zero (normal) CACS for identifying patients at acceptable low risk for future cardiovascular events who might be safely discharged home from the ED. Methods We searched multiple databases for longitudinal studies of CACS in symptomatic patients without known coronary artery disease that reported major adverse cardiovascular events (MACEs), including death and myocardial infarction. Pooled risk ratios, sensitivity, specificity, and likelihood ratios were analyzed. Results Eight studies evaluated 3,556 patients, with a median follow-up of 10.5 months. Pooled prevalence of zero CACS was 60%. Patients with CACS=0 had a significantly lower risk of cardiovascular events compared with those with CACS greater than 0 (MACEs: relative risk 0.06, 95% confidence interval 0.04 to 0.11, I2=0%; death/myocardial infarction: relative risk 0.19; 95% confidence interval 0.08 to 0.47, I2=0%). The pooled event rates for CACS=0 (MACEs 0.8%/year; death/myocardial infarction 0.5%/year) were significantly lower than for CACS greater than 0 (MACEs 14.6%/year; death/myocardial infarction 3.5%/year). Analysis of summary testing parameters showed a sensitivity of 96%, specificity of 60%, positive likelihood ratio of 2.36, and negative likelihood ratio of 0.07. Conclusion Acute chest pain patients without history of coronary artery disease, ischemic ECG changes, or increased cardiac enzyme levels commonly have a CACS of zero, with a very low subsequent risk of MACEs or death or myocardial infarction. This meta-analysis proffers the potential role of initial CACS testing for avoiding unnecessary hospitalization and further cardiac testing in acute chest pain patients with a CACS of zero.

Introduction: Higher central elastic artery stiffness is associated with greater brain white matter hyperintensity volume and lower cognitive performance in older adults. However, it is unknown if higher central artery stiffness is related to regional decreases in brain white matter integrity (WMI) and reductions in working memory or processing speed. We hypothesized that greater large elastic artery stiffness would be associated with lower working memory and slower processing speed as well as lower regional WMI in older adults. Methods: In young (n=19; 23.8 ± 0.7 yrs) and older (n=22; 64.4 ± 4.2 yrs; range 60-71 yrs) healthy adults, aortic stiffness (carotid-femoral pulse wave velocity, cfPWV, via tonometry) and carotid artery compliance and β-stiffness index (carotid artery ultrasound and tonometry) were determined non-invasively. WMI was assessed by fractional anisotrophy (FA) (3T MRI) from diffusion tensor images. An N-Back task and letter and pattern comparison tests were performed as measures of working memory and processing speed, respectively. d’Prime, a measure of signal detection, was calculated on the N-Back task as a ratio of positive ‘hits’ to ‘false alarm’ responses. Results: cfPWV (8.4 ± 0.5 vs. 5.2 ± 0.2 m/sec, P Conclusions: Our results suggest that lower carotid artery compliance and greater β-stiffness are associated with reduced working memory performance and slower processing speed but not regional WMI in older adults.

Little data exists on whether the physicians' skills in responding to cardiac arrest are fully developed after the advanced cardiac life support (ACLS) course, or if there is a significant improvement in their performance after an initial learning curve.To estimate the effect of physician experience on the results of prehospital cardiac arrests.Prospective data were collected on all prehospital resuscitative attempts in the area by ACLS-trained ambulance physicians.Of 232 attempted cardiac resuscitations, 96 (41%) patients survived to hospital admission and 44 (19%) were discharged alive. A group of 39 physicians responded to from one up to 29 cases with a mean of four cases. Physicians responding to five or fewer cases had a trend to fewer patients surviving to admission compared with those responding to six or more (36 vs. 45%, P=0.31) but no difference was found on survival to discharge (19 vs. 20%, P=0.87).In this study, resuscitative experience of the physician did not have a significant effect on survival suggesting that experience does not significantly add to the current ACLS training in responding to ventricular fibrillation/ventricular tachycardia. More studies are needed.

Background: Radiofrequency ablation of atrial flutter is a commonly performed procedure. Ablation success depends upon complete transmural atrial tissue injury to achieve bidirectional cavotricuspid isthmus (CTI) block. Transmural ablation increases risk of injury to the adjacent right coronary artery (RCA). Distance between the RCA and the endocardium within the CTI area is not well described. We aimed to perform in vivo measurements of the distance between the CTI area and adjacent RCA. Methods: Thirty-three consecutive patients underwent electrocardiogram-gated contrast-enhanced computed tomography. CTI area was divided into nine segments based on three common catheter locations (paraseptal, central, and lateral or 5, 6, and 7 o'clock) and ventricular to atrial ablation line. Results: Mean age was 64 ± 11 years and 97% of the participants were male. Paraseptal, central, and lateral measurements at the tricuspid annulus ridge showed endocardial to RCA distance 9 ± 3, 6 ± 2, and 5 ± 3 mm, respectively (range 2–17 mm). Corresponding measurements for the ventricular side were 5 ± 3, 4 ± 2, and 4 ± 2 mm and atrial side measurements were 3 ± 2, 3 ± 2, and 3 ± 3 mm. Distance was ≤2 mm in 14% of segments on the ventricular side and 39% of segments on the atrial side. Paired t-test showed significant difference (P < 0.001) between tricuspid annulus ridge measurements and adjacent atrial or ventricular measurements. Conclusions: Distance between endocardium and RCA lumen is reduced in areas adjacent to the tricuspid annulus ridge. (PACE 2010; 1319–1323)

Reliable assessment of left ventricular size and systolic function has important prognostic and therapeutic implications for patients with heart disease. CT technology is advancing rapidly and can be used for noninvasive assessment of the coronary anatomy. Without additional radiation or contrast, the already acquired image data set can be used for analysis of left ventricular size, mass, and systolic function. In comparison with other noninvasive modalities, multidetector CT has superior spatial resolution but temporal resolution has suffered. Recent advances, including multisegment reconstruction and dual-source scanning, have improved the temporal resolution substantially. MRI is the current gold standard for assessing the left ventricle. Many small comparative studies suggest that CT has good agreement with MRI and that it could potentially replace MRI in some patients, especially those with internal cardiac devices. The use of CT to assess ventricular remodeling is limited by the use of contrast and radiation, but its widespread availability, ease of use, and improved temporal resolution suggest that multidetector CT will have expansive use in the future.

Objective The objective of this study is to compare the use of transesophageal echocardiography (TEE) vs multidetector computed tomography (MDCT) for detecting pulmonary vein stenosis. Background Pulmonary vein isolation is increasingly used to treat atrial fibrillation. Pulmonary vein stenosis remains a potential complication of pulmonary vein isolation and ideal methods for detection of stenosis are still to be determined. Methods Thirty-six subjects who underwent pulmonary vein isolation returned for follow-up MDCT and TEE. Percent diameter loss was reported for each pulmonary vein stenosis by MDCT. A 50% narrowing was considered as an indication of a stenosis. Pulsed-wave Doppler using TEE was used to measure peak velocities of all pulmonary veins. Results Multidetector computed tomography and TEE were performed in all subjects (58 ± 10 years) at 4 ± 2 months after pulmonary vein isolation. Atrial fibrillation was present in 14% at time of follow-up. Multidetector computed tomography was able to evaluate all 4 (100%) pulmonary veins in 36 subjects, whereas full interrogation by TEE was possible in 138 (96%) of 144 veins. Pulmonary vein stenosis >50% by MDCT was present in 7 pulmonary veins. Analysis of the receiver operating curve for TEE showed that it had optimum detection of pulmonary vein stenosis at peak velocities ∼100 cm/s with 86% sensitivity and 95% specificity. Area under the curve for TEE was 0.93. Clinically significant stenosis was observed in 2 subjects and was detected by both TEE and MDCT. Conclusions Transesophageal echocardiography was able to detect most pulmonary veins with good sensitivity and specificity in comparison to MDCT. Pulmonary veins may be visualized more frequently by MDCT; however, TEE provides additional data about the functional significance of a pulmonary vein stenosis.

Background.Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men.Methods.We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial.Results.Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex.Conclusions.Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

ObjectivesThis study sought to determine whether multidetector computed tomography (MDCT) may be able to detect occlusive coronary disease in transplanted hearts.BackgroundIn heart transplant recipients, asymptomatic coronary disease requiring frequent surveillance commonly develops. Recent advancements in MDCT allow for noninvasive assessment of the coronary vessels.MethodsElectrocardiogram-gated contrast-enhanced MDCT scans (16 × 0.75-mm detectors, 420 ms rotation, 100 ml contrast) with multisegment reconstruction were performed on 54 transplant recipients within 6 ± 11 days of quantitative coronary angiography (QCA). Heart rate at the time of the scan was 90 ± 11 beats/min. Coronary arterial segments >1.5 mm in diameter were analyzed by independent investigators.ResultsThere was a good correlation between MDCT and QCA percent stenosis (r = 0.75, p < 0.01, SEE = 15%). Of the 791 segments identified by QCA, 754 (95%) were analyzable by MDCT. The sensitivity, specificity, and positive and negative predictive values of MDCT compared with QCA for the detection of segments with significant (>50%) stenosis were 86%, 99%, 81%, and 99%, respectively. The MDCT correctly identified 15 of the 16 (94%) transplant patients classified by QCA as having occlusive coronary artery disease and 29 of the 37 patients without significant stenosis (78%). In 1 patient who received intravenous beta-blockers, transient bradycardia requiring temporary pacing developed, but there were no other complications.ConclusionsDetection of occlusive coronary disease in heart transplant recipients with elevated resting heart rate by MDCT is feasible using multicycle reconstruction. The need for surveillance invasive coronary angiography in transplant recipients might be mitigated by use of MDCT.

The optimal pacing site in cardiac resynchronization therapy (CRT) remains controversial. Tissue synchronization imaging is a novel echocardiographic technique that color-codes for areas of maximal delay in myocardial velocities. This study aimed to identify whether the left ventricular (LV) pacing lead position in CRT should be guided by a patient's area of maximal mechanical delay. Fifty-four patients with advanced heart failure were assessed echocardiographically before and 6 months after CRT. Response was analyzed according to the relation between the LV lead position and the area of maximal delay to peak velocity by tissue synchronization imaging in the first half of the ejection phase: group 1 (n = 22) had lead placement corresponding to the segment of maximal delay; group 2 (n = 13) had lead placement 1 segment adjacent; and group 3 (n = 19) had lead placement remote from this site. Evidence of LV reverse remodeling and improved systolic function was documented in group 1 (mean percentage decrease in end-systolic volume 23%) more than in group 2 (mean decrease 15%), and more than in group 3 (mean increase 8.9%, p0.0001 compared with groups 1 and 2). In group 1, 16 of 22 patients had reverse remodeling (15% decrease in end-systolic volume); reverse remodeling was seen in 7 of 13 patients in group 2 and 1 of 19 in group 3. The placing of the lead position proximal to the site of maximal delay by tissue synchronization imaging was correlated with reverse remodeling (r = 0.449, p = 001). Of 7 patients with delay confined to the septum and anterior wall only, none had evidence of reverse remodeling after CRT. In conclusion, pacing at the site of maximal mechanical delay was associated with reverse remodeling. Individually tailored LV lead positioning should be considered before CRT.

The inspiratory impedance threshold device (ITD) has been shown to improve hemodynamic variables and survival outcomes during cardiopulmonary resuscitation in animals and humans. We hypothesized that use of an ITD, with a resistance of -10 cm H2O, will improve hemodynamics and short-term survival rates during hypovolemic hypotension in spontaneously breathing pigs.Female farm pigs ( approximately 26 kg) were intubated and anesthetized with propofol with the dose adjusted to permit spontaneous respirations. They were bled to 50% of calculated blood volume through an arterial catheter and then prospectively randomized to either treatment with an ITD or observation alone. Arterial and intratracheal pressures as well as arterial blood gases were measured. After 90 min the ITD was removed, normal saline was administered to all surviving animals, the anesthetic was discontinued, and animals were allowed to recover. Statistical analysis was performed with one-way repeated ANOVA and survival rates were calculated with Kaplan-Meier analysis.Treatment with the ITD resulted in lower intratracheal inspiratory pressure in the treatment group (-11+/-0.4 mmHg versus -4+/-0.7 mmHg, respectively, P0.005). Mean arterial pressure after 30 min of treatment with the ITD was higher in the treatment group (61.1+/-5.5 mmHg versus 37.4+/-2.1 mmHg, respectively, P0.005). All pigs in the control group died within 65 min of the initial bleed, whereas 7/8 (87%) treated with an ITD survived for90 min (P0.001). During the recovery phase, 6/8 (75%) in the ITD group survived for3h and awoke without neurological deficit; one surviving animal in the ITD group never woke up. Arterial oxygenation was not compromised in the ITD group.Use of an ITD improved blood pressure and short-term survival rates in a spontaneously breathing porcine model of hypovolemic hypotension.

ObjectivesA rapid, ice-cold saline flush combined with active compression-decompression (ACD) plus an inspiratory impedance threshold device (ITD) cardiopulmonary resusitation (CPR) will cool brain tissue more effectively than with standard CPR (S-CPR) during cardiac arrest (CA).BackgroundEarly institution of hypothermia after CPR and return of spontaneous circulation improves survival and outcomes after CA in humans.MethodsVentricular fibrillation (VF) was induced for 8 min in anesthetized and tracheally intubated pigs. Pigs were randomized to receive either ACD + ITD CPR (n = 8) or S-CPR (n = 8). After 2 min of CPR, 30 ml/kg ice-cold saline (3°C) was infused over the next 3 min of CPR via femoral vein followed by up to three defibrillation attempts (150 J, biphasic). If VF persisted, epinephrine (40 μg/kg) and vasopressin (0.3 U/kg) were administered followed by three additional defibrillation attempts. Hemodynamic variables and temperatures were continuously recorded.ResultsAll ACD + ITD CPR pigs (8 of 8) survived (defined as 15 min of return of spontaneous circulation [ROSC]) versus 3 of 8 pigs with S-CPR (p < 0.05). In survivors, brain temperature (°C) measured at 2-cm depth in brain cortex 1 min after ROSC decreased from 37.6 ± 0.2 to 35.8 ± 0.3 in ACD + ITD CPR versus 37.8 ± 0.2 to 37.3 ± 0.3 in S-CPR (p < 0.005). Immediately before defibrillation: 1) right atrial systolic/diastolic pressures (mm Hg) were lower (85 ± 19, 4 ± 1) in ACD + ITD CPR than S-CPR pigs (141 ± 12, 8 ± 3, p < 0.01); and 2) coronary perfusion pressures (mm Hg) were higher in ACD + ITD CPR (28.3 ± 2) than S-CPR pigs (17.4 ± 3, p < 0.01).ConclusionsA rapid ice-cold saline infusion combined with ACD + ITD CPR during cardiac arrest induces cerebral hypothermia more rapidly immediately after ROSC than with S-CPR.

A 37-year-old man who recently underwent aortic valve replacement after endocarditis presented with cardiogenic shock. A large expansile pseudoaneurysm was subsequently discovered using multiple imaging modalities. Although transesophageal echocardiography is important in diagnosing valve endocarditis, coronary CT angiography of prosthetic valves is feasible and image quality is good. In this case, coronary CT angiography allowed for better understanding of transesophageal echocardiography images and earlier diagnosis of coronary involvement as cause for left ventricular dysfunction.

Recent data suggest that generation of negative intrathoracic pressure during the decompression phase of CPR improves hemodynamics, organ perfusion and survival.Incomplete chest wall recoil during the decompression phase of standard CPR increases intrathoracic pressure and right atrial pressure, impedes venous return, decreases compression-induced aortic pressures and results in a decrease of mean arterial pressure, coronary and cerebral perfusion pressure.Nine pigs in ventricular fibrillation (VF) for 6 min, were treated with an automated compression/decompression device with a compression rate of 100 min(-1), a depth of 25% of the anterior-posterior diameter, and a compression to ventilation ratio of 15:2 with 100% decompression (standard CPR) for 3 min. Compression was then reduced to 75% of complete decompression for 1 min of CPR and then restored for another 1 min of CPR to 100% full decompression. Coronary perfusion pressure (CPP) was calculated as the diastolic (aortic (Ao)-right atrial (RA) pressure). Cerebral perfusion pressure (CerPP) was calculated multiple ways: (1) the positive area (in mmHg s) between aortic pressure and intracranial pressure (ICP) waveforms, (2) the coincident difference in systolic and diastolic aortic and intracranial pressures (mmHg), and (3) CerPP = MAP--ICP. ANOVA was used for statistical analysis and all values were expressed as mean +/- S.E.M. The power of the study for an alpha level of significance set at 0.05 was0.90.With CPR performed with 100%-75%-100% of complete chest wall recoil, respectively, the CPP was 23.3 +/- 1.9, 15.1 +/- 1.6, 16.6 +/- 1.9, p = 0.003; CerPP was: (1) area: 313.8 +/- 104, 89.2 +/- 39, 170.5 +/- 42.9, p = 0.03, (2) systolic aortic minus intracranial pressure difference: 22.8 +/- 3.6, 16.5 +/- 4, 23.7 +/- 4.5, p = n.s., and diastolic pressure difference: 5.7 +/- 3, -2.4 +/- 2.4, 3.2 +/- 2.5, p = 0.04 and (3) mean: 14.3 +/- 3, 7 +/- 2.9, 12.4 +/- 2.9, p = 0.03, diastolic aortic pressure was 28.1 +/- 2.5, 20.7 +/- 1.9, 20.9 +/- 2.1, p = 0.0125; ICP during decompression was 22.8 +/- 1.7, 23 +/- 1.5, 19.7 +/- 1.7, p = n.s. and mean ICP was 37.1 +/- 2.3, 35.5 +/- 2.2, 35.2 +/- 2.4, p = n.s.; RA diastolic pressure 4.8 +/- 1.3, 5.6 +/- 1.2, 4.3 +/- 1.2 p = 0.1; MAP was 52 +/- 2.9, 43.3 +/- 3, 48.3 +/- 2.9, p = 0.04; decompression endotracheal pressure, -0.7 +/- 0.1, -0.3 +/- 0.1, -0.75 +/- 0.1, p = 0.045.Incomplete chest wall recoil during the decompression phase of CPR increases endotracheal pressure, impedes venous return and decreases mean arterial pressure, and coronary and cerebral perfusion pressures.

Background:The basic premise that frequent ventilations during cardiopulmonary resuscitation (CPR) are a necessity for tissue oxygenation has recently been challenged. An inspiratory impedance threshold device (ITD) recently has also been shown to increase CPR efficiency, principally by augmenting circulation with little impact on ventilation. The optimal compression to ventilation (C/V) is not known for this new device. The purpose of this study was to compare the currently recommended C/V ratio of 5:1 with a 10:1 ratio, ± the ITD, to optimize circulation and oxygenation during CPR. Methods: Thirty-two adult pigs weighing 26–31 kg were randomized to CPR with varying C/V ratios ± the ITD as follows: A = 5:1, B = 5:1 + ITD, C = 10:1, D = 10:1 + ITD. After 6 min of untreated ventricular fibrillation (VF), closed-chest standard CPR was performed with an automatic piston device that does not impede passive chest wall recoil, at a continuous compression rate of 100 min −1 . Synchronous breaths were given every 5 or 10 compressions during the decompression phase depending on the group. CPR was performed for 6 min and physiological variables were measured throughout the experimental protocol. Results: A reduction in the frequency of ventilation from 5:1 to 10:1 resulted in significantly improved arterial and coronary perfusion pressure in a pig model of cardiac arrest. Addition of an ITD resulted in further increases in arterial and coronary perfusion pressures with both 5:1 and 10:1 C/V ratios, without compromising oxygenation. Conclusion: CPR efficiency can be optimized by changing the compression: ventilation ratio from 5:1 to 10:1 and with concurrent use of the inspiratory threshold device. © 2004 Published by Elsevier Ireland Ltd.

Purpose of review Recent advances in cardiopulmonary resuscitation have shed light on the importance of cardiorespiratory interactions during shock and cardiac arrest. This review focuses on recently published studies that evaluate factors that determine preload during chest compression, methods that can augment preload, and the detrimental effects of hyperventilation and interrupting chest compressions. Recent findings Refilling of the ventricles, so-called ventricular preload, is diminished during cardiovascular collapse and resuscitation from cardiac arrest. In light of the potential detrimental effects and challenges of large-volume fluid resuscitations, other methods have increasing importance. During cardiac arrest, active decompression of the chest and impedance of inspiratory airflow during the recoil of the chest work by increasing negative intrathoracic pressure and, hence, increase refilling of the ventricles and increase cardiac preload, with improvement in survival. Conversely, increased frequency of ventilation has detrimental effects on coronary perfusion pressure and survival rates in cardiac arrest and severe shock. Prolonged interruption of chest compressions for delivering single-rescuer ventilation or analyzing rhythm before shock delivery is associated with decreased survival rate. Summary Cardiorespiratory interactions are of profound importance in states of cardiovascular collapse in which increased negative intrathoracic pressure during decompression of the chest has a favorable effect and increased intrathoracic pressure with ventilation has a detrimental effect on survival rate.

Fabry's disease is a rare but important cause of structural cardiac disease that may influence cardiac surgical decision making. Herein we present a case of mitral valve repair in a patient with Fabry's disease and review the cardiac-related literature on this lysosomal storage disease.

Background: Transcatheter aortic valve replacement (TAVR) has been established as a valid option for patient with symptomatic severe aortic stenosis (AS) deemed ineligible or too high-risk for surgical treatment. The prognostic value of right ventricular (RV) function in this group of patients is

[Figure][1] [Online Video 1][2] Severe ostial stenosis of the left main coronary artery depicted in a caudal left anterior oblique view. ![Figure][1] [Online Video 2][3] A caudal right anterior oblique view demonstrating the close proximity of the enlarged pulmonary artery to the

BACKGROUND In clinical practice, heart failure (HF) medications are underused and prescribed at lower than recommended doses. Telephone care is an option that could help to titrate HF medication in a timely manner. We describe our experience of a nurse-run, cardiologist- or nurse practitioner-supervised clinic to up-titrate HF medications via telephone. METHODS Patients with the diagnosis of HF, New York Heart Association classes I to III, were referred to a registered nurse-run, cardiologist-/nurse practitioner-supervised HF medication titration clinic. Clinical and medication data collected at enrollment to the clinic and at 3 to 6 months after optimization of HF medications in patients who did or did not reach the target doses were compared. Effect on left ventricular (LV) function was also evaluated. RESULTS There were 79 patients in the evaluation: 64 with HF and LV systolic dysfunction (LVSD) and the remaining 15 with HF and preserved ejection fraction (EF). Seventy-two percent of patients with LVSD were on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 61% were on a β-blocker at baseline, and this increased to 98% and 97%, respectively, after optimization. Target doses was achieved in 50% of patients for ACEI or ARB, and in 41% for β-blockers. The median time to optimization was 54 days (interquartile range, 20-97 days). The average number of phone calls at the time of optimization were 5.4 (SD, 3.7), and the average number of clinic visits was 1.9 (SD, 1.3). Reasons for not reaching the target doses included hypotension, hyperkalemia, and renal dysfunction for ACEI and bradycardia for β-blockers. Overall, the EF increased by 10% (SD, 10%) after 6 months, and 35% or greater in 42% of patients whose baseline EF was less than 35%. There were no adverse events related to the dose up-titration. CONCLUSION Telephonic titration of HF medications was feasible and safe and was achieved in 97% patients on ACEI/ARB and β-blockers. Medication titration was associated with significant improvement in LV function, avoiding the need for device therapy in many patients.

Computed tomography (CT) is the gold standard for assessing pulmonary vein (PV) anatomy and stenosis after ablation for atrial fibrillation (AF), but radiation exposure can be a concern. Transesophageal echocardiography (TEE) provides anatomic and functional assessment of the PVs, although no study has prospectively compared findings on TEE with those on CT.The Role of Transesophageal Echocardiography Compared to Computed Tomography in Evaluation of Pulmonary Vein Ablation for Atrial Fibrillation (ROTEA) study was a prospective, single-blinded observational study of patients with paroxysmal or persistent AF undergoing ablation. TEE and CT were performed immediately before and 3 months after AF ablation. The study included 43 patients (84% men; mean age, 56 ± 11 years).In the preprocedural study, TEE identified 98% of PVs with adequate Doppler measurements obtained. After ablation, no moderate or severe PV stenosis was detected on CT, and a 30% to 50% reduction in luminal diameter was seen in 5% of studied veins. Functional PV stenosis by pulsed-wave Doppler was seen in two veins on TEE. PV diameters decreased after ablation by 0.20 ± 0.03 and 0.22 ± 0.03 cm as measured by CT and TEE, respectively (P.001). However, TEE underestimated PV ostial dimensions compared with CT, especially for the inferior PVs. Severe spontaneous echo contrast and low left atrial appendage emptying velocities, were identified in 10% of patients in sinus rhythm after ablation.In the ROTEA study, TEE was feasible in assessing PVs before and after ablation, providing both anatomic and functional information that complemented CT. PV ostial dimensions after ablation can be monitored using either modality, although TEE underestimates PV dimensions, especially for the inferior veins.

Radiofrequency ablation of atrial flutter is a commonly performed procedure. Ablation success depends upon complete transmural atrial tissue injury to achieve bidirectional cavotricuspid isthmus (CTI) block. Transmural ablation increases risk of injury to the adjacent right coronary artery (RCA). Distance between the RCA and the endocardium within the CTI area is not well described. We aimed to perform in vivo measurements of the distance between the CTI area and adjacent RCA.Thirty-three consecutive patients underwent electrocardiogram-gated contrast-enhanced computed tomography. CTI area was divided into nine segments based on three common catheter locations (paraseptal, central, and lateral or 5, 6, and 7 o'clock) and ventricular to atrial ablation line.Mean age was 64 ± 11 years and 97% of the participants were male. Paraseptal, central, and lateral measurements at the tricuspid annulus ridge showed endocardial to RCA distance 9 ± 3, 6 ± 2, and 5 ± 3 mm, respectively (range 2-17 mm). Corresponding measurements for the ventricular side were 5 ± 3, 4 ± 2, and 4 ± 2 mm and atrial side measurements were 3 ± 2, 3 ± 2, and 3 ± 3 mm. Distance was ≤2 mm in 14% of segments on the ventricular side and 39% of segments on the atrial side. Paired t-test showed significant difference (P0.001) between tricuspid annulus ridge measurements and adjacent atrial or ventricular measurements.Distance between endocardium and RCA lumen is reduced in areas adjacent to the tricuspid annulus ridge.

Contrast enhanced computed tomography (CT) is able to assess coronary stenosis and left ventricular function. Due to first pass effect it is able to assess surrogate markers of myocardial perfusion. We assessed the hypothesis that computed tomography can detect hibernating myocardium. Methods and results: A well-established porcine model of hibernating myocardium was used for this study. In this model of chronic coronary stenosis there is ~20% reduction in regional myocardial perfusion. Six pigs underwent instrumentation of the proximal left anterior descending (LAD) coronary artery with an external constrictor. Paired Student-T test was used to compare LAD territory and opposite myocardial segments. After 12 weeks echocardiographic studies detected regional left ventricular dysfunction by M-mode to the LAD territory (Table ). At that time EKG guided computed tomography showed severe stenosis to the LAD. Myocardial signal density (MSD) by CT was assessed in 24 opposing segments during diastole (Hounsfield Units). MSD within the territory of the LAD was significantly lower than MSD of opposing segments (Table ). Ratio of signal density (RSD) between myocardium and left ventricular cavity was significantly lower within the LAD territory in comparison to opposing segments (Table ). Conclusion: In a well-established porcine model of hibernating myocardium contrast enhanced computed tomography was able to detect areas of decreased attenuation suggesting that CT might be able to detect hibernating myocardium. Table

Summary We have demonstrated previously that carriers of a genotype called C4B*Q0 (silent allele of the C4B gene) have a substantially increased risk to suffer from myocardial infarction or stroke, and are selected out from the healthy elderly population. Because smoking carries a major risk for cardiovascular disease (CVD), it seemed worthwhile to study if these two factors interact. Study 1 involved 74 patients with angina pectoris (AP), 85 patients with recent acute myocardial infarction (AMI) and 112 survivors of a previous AMI and 382 controls from Iceland. Study 2 involved 233 patients with severe CVD and 274 controls from Hungary. Smoking habits were registered for each subject. The number of C4A and C4B genes was determined by phenotyping or genotyping. Compared to controls, C4B*Q0 carrier frequency was significantly higher at diagnosis in Icelandic smokers with AP (P = 0·005) and AMI (P = 0·0003) and Hungarian smokers with severe coronary artery disease (P = 0·023), while no such difference was observed in non-smoking subjects. Age-associated decrease in C4B*Q0 observed previously in two remote Caucasian populations was found, in the present study, to be associated strongly with smoking, and to already occur in smokers after age 50 years both in Iceland and Hungary. Our findings indicate that the C4B*Q0 genotype can be considered as a major covariate of smoking in precipitating the risk for AMI and associated deaths.