"Bringing on the light" in a complex clinical scenario: Optical coherence tomography-guided discontinuation of antiplatelet therapy in cancer patients with coronary artery disease (PROTECT-OCT registry).

BACKGROUND: Cancer patients with recently placed drug-eluting stents (DESs) often require premature dual antiplatelet therapy (DAPT) discontinuation for cancer-related procedures. Optical coherence tomography (OCT) can identify risk factors for stent thrombosis such as stent malapposition, incomplete strut coverage and in-stent restenosis and may help guide discontinuation of DAPT. METHODS: We conducted a single-center prospective study in cancer patients with recently placed (1-12 months) DES who required premature DAPT discontinuation. Patients were evaluated with diagnostic coronary angiogram and OCT. Individuals with appropriate stent strut coverage, expansion, apposition, and absence of in-stent restenosis or intraluminal masses were considered low risk and transiently discontinued DAPT to allow optimal cancer therapy. Patients who did not meet all these criteria were considered high risk and underwent further endovascular treatment when appropriate and bridging with low-molecular weight heparin. The incidence of adverse cardiovascular events was assessed after the procedure and at 12 months. RESULTS: A total of 40 patients were included. Twenty-seven patients (68%) were considered low risk by OCT criteria and DAPT was transiently discontinued. Thirteen patients (32%) were considered high risk with one or more OCT findings: uncovered stent struts (4 patients, 10%); stent underexpansion (3 patients, 8%); malapposition (8 patients, 20%); in-stent restenosis (2 patients, 5%). The high-risk patients with uncovered stent struts and malapposition underwent additional stent dilatation. There were no cardiovascular events in the low-risk group. One myocardial infarction occurred in the high-risk group. Fourteen non-cardiac deaths were registered before 12 months due to cancer progression or cancer therapy. CONCLUSION: OCT imaging allows identification of low-risk cancer patients with DES placed who may safely discontinue DAPT and proceed with cancer-related surgery or procedures.

Risk factor burden and control at the time of admission in patients with acute myocardial infarction: Results from the NCDR.

BACKGROUND: Understanding risk factor burden and control as well as perceived risk prior to acute myocardial infarction (MI) presentation may identify gaps in contemporary systems of care. METHODS: Patients presenting with MI in the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry--Get With the Guidelines between January 2007 and November 2013 (N = 443,117) were stratified into 5 mutually exclusive risk categories: Framingham Risk Score (FRS) <10% 74,990 (16.9%), FRS 10% to 20% 90,429 (20.4%), FRS >20% 25,701 (5.8%), diabetes without cardiovascular disease (CVD) 67,779 (15.3%), and prior CVD 184,218 (41.6%). Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (non-HDL-C) goals and statin eligibility were determined based on the Third Adult Treatment Panel. RESULTS: At presentation, 66.3% met the low-density lipoprotein cholesterol goal, 66.8% met the non-HDL-C goal, 63.7% were nonsmokers, and 65.1% of patients with prior CVD were on aspirin. Only 36.1% of patients met all assessed risk factor control metrics. Overall statin eligibility prior to MI was 60.8%, and 61.1% of statin-eligible patients reported statin use. CONCLUSION: Risk factor control prior to MI was suboptimal, with the majority of individuals failing to meet at least 1 risk factor control metric. More effective system-based interventions are needed to promote adherence to prevention targets.

Defining coronary artery calcium concordance and repeatability - Implications for development and change: The Dallas Heart Study.

BACKGROUND: Development and change of coronary artery calcium (CAC) are associated with coronary heart disease. Interpretation of serial CAC measurements will require better understanding of changes in CAC beyond the variability in the test itself. METHODS: Dallas Heart Study participants (2888) with duplicate CAC scans obtained minutes apart were analyzed to determine interscan concordance and 95% confidence bounds (ie: repeatability limits) for each discrete CAC value. These data derived cutoffs were then used to define change above measurement variation and determine the frequency of CAC development and change among 1779 subjects with follow up CAC scans performed 6.9 years later. RESULTS: Binary concordance (0 vs. >0) was 91%. The value of CAC denoting true development of CAC by exceeding the 95% confidence bounds for a single score of 0 was 2.7 Agatston units (AU). Among those with scores >0, the 95% confidence bounds for CAC change were determined by the following formulas: for CAC≤100AU: 5.6√CAC + 0.3*CAC - 3.1; for CAC>100AU: 12.4√CAC - 67.7. Using these parameters, CAC development occurred in 15.0% and CAC change occurred in 48.9%. Although 225 individuals (24.9%) had a decrease in CAC over follow up, only 1 (0.1%) crossed the lower confidence bound. Compared with prior reported definition of CAC development (ie: >0), the novel threshold of 2.7AU resulted in better measures of model performance. In contrast, for CAC change, no consistent differences in performance metrics were observed compared with previously reported definitions. CONCLUSION: There is significant interscan variability in CAC measurement, including around scores of 0. Incorporating repeatability estimates may help discern true differences from those due to measurement variability, an approach that may enhance determination of CAC development and change.

Progression of CAC Score and Risk of Incident CVD.

OBJECTIVES: The authors sought to determine the relative contributions of baseline coronary artery calcification (CAC), follow-up CAC, and CAC progression on incident cardiovascular disease (CVD). BACKGROUND: Repeat CAC scanning has been proposed as a method to track progression of total atherosclerotic burden. However, whether CAC progression is a useful predictor of future CVD events remains unclear. METHODS: This was a prospective observational study of 5,933 participants free of CVD who underwent 2 examinations, including CAC scores, and subsequent CVD event assessment. CAC progression was calculated using the square root method. The primary outcome was total CVD events (CVD death, nonfatal myocardial infarction, nonfatal atherosclerotic stroke, coronary artery bypass surgery, percutaneous coronary intervention). Secondary outcomes included hard CVD events, total coronary heart disease (CHD) events, and hard CHD events. RESULTS: CAC was detected at baseline in 2,870 individuals (48%). The average time between scans was 3.5 ± 2.0 years. After their second scan, 161 individuals experienced a total CVD event during a mean follow-up of 7.3 years. CAC progression was significantly associated with total CVD events (hazard ratio: 1.14, 95% confidence interval: 1.01 to 1.30 per interquartile range; p = 0.042) in the model including baseline CAC, but the contribution of CAC progression was small relative to baseline CAC (chi-square 4.16 vs. 65.92). Furthermore, CAC progression was not associated with total CVD events in the model including follow-up CAC instead of baseline CAC (hazard ratio: 1.05, 95% confidence interval: 0.92 to 1.21; p = 0.475). A model that included follow-up CAC alone performed as well as the model that included baseline CAC and CAC progression. CONCLUSIONS: Although CAC progression was independently, but modestly, associated with CVD outcomes, this relationship was no longer significant when including follow-up CAC in the model. These findings imply that if serial CAC scanning is performed, the latest scan should be used for risk assessment, and in this context, CAC progression provides no additional prognostic information.

Immediate and intermediate-term results of optical coherence tomography guided atherectomy in the treatment of peripheral arterial disease: Initial results from the VISION trial.

BACKGROUND: Long-term patency rates for percutaneous peripheral arterial interventions are suboptimal. Optical coherence tomography (OCT) guided atherectomy may yield superior patency by optimizing plaque removal while preserving the tunica media and adventitia. METHODS: The VISION study is a multicenter prospective study of patients with peripheral arterial disease undergoing OCT guided atherectomy with the Pantheris™ device. In 11 patients enrolled in a single center, we report procedural and clinical outcomes, at 30days and 6months. RESULTS: The mean age was 63±11years and 73% (n=8) were men. The target lesion was in the superficial femoral artery in 82% (n=9) of the patients. Mean stenosis severity was 87%±10% and mean lesion length was 39±31mm. Procedural success was observed in all patients with no device related complications. Mean post-atherectomy stenosis was 18%±15%. Almost all excised tissue consisted of intimal plaque (94%). At 30days, significant improvements in Rutherford class, VascuQoL scores and ABI were observed, 0.9±0.8 vs. 3.1±0.7 (p=0.01), 4.9±1.9 vs. 3.6±1.5 (p=0.03) and 1.04±0.19 vs. 0.80±0.19 (p<0.01) respectively. At 6months, there were significant improvements in Rutherford class (1.0±1.0 vs. 3.1±0.7, p=0.01) and ABI (0.93±0.19 versus 0.80±0.19, p=0.02) but not in VascuQoL scores (3.7±1.4 versus 3.6±1.5, p=0.48). Target lesion revascularization occurred in 18% (n=2) of the patients. CONCLUSION: OCT guided atherectomy resulted in high procedural success, no device related complications and encouraging results up to 6months. Histological analysis suggested little injury to the media and adventitia. Larger studies are needed to confirm the efficacy of this approach.

Coronary Artery Calcium Improves Risk Classification in Younger Populations.

OBJECTIVES: This study sought to assess the effect of coronary artery calcium (CAC) on coronary heart disease (CHD) risk prediction in a younger population. BACKGROUND: CAC measured by computed tomography improves CHD risk classification in older adults, but the effectiveness of CAC in younger populations has not been fully assessed. METHODS: In the DHS (Dallas Heart Study), a multiethnic probability-based population sample, traditional CHD risk factors and CAC were measured in participants without baseline cardiovascular disease or diabetes. Incident CHD-defined as CHD death, myocardial infarction, or coronary revascularization-was assessed over a median follow-up of 9.2 years. Predicted CHD risk was assessed with a Weibull model inclusive of traditional risk factors before and after the addition of CAC as ln(CAC + 1). Participants were divided into 3 10-year risk categories, <6%, 6% to <20%, and ≥20%, and the net reclassification improvement (NRI) was calculated. We also performed a random-effects meta-analysis of NRI from previous studies inclusive of older individuals. RESULTS: The analysis comprised 2,084 participants; mean age was 44.4 ± 9.0 years. CAC was independently associated with incident CHD (hazard ratio per SD: 1.90, 95% confidence interval [CI] 1.51 to 2.38; p < 0.001). The addition of CAC to the traditional risk factor model resulted in significant improvement in the C-statistic (delta = 0.03; p = 0.003). Among participants with CHD events, the addition of CAC resulted in net correct upward reclassification of 21%, and among those without CHD, a net correct downward reclassification of 0.5% (NRI: 0.216, p = 0.012). Results remained significant when the outcome was restricted to CHD death and myocardial infarction and when individuals with diabetes were included. The NRI observed in this study was similar to the pooled estimate from previous studies (0.200, 95% CI: 0.140 to 0.258) and the addition of our study to the meta-analysis did not result in significant heterogeneity (I(2) = 0%). CONCLUSIONS: CAC scoring also improves CHD risk classification in younger adults.

Cardiovascular lifetime risk predicts incidence of coronary calcification in individuals with low short-term risk: the Dallas Heart Study.

BACKGROUND: The absence of coronary artery calcium (CAC) in middle age is associated with very low short-term risk for coronary events. However, the long-term implications of a CAC score of 0 are uncertain, particularly among individuals with high cardiovascular lifetime risk. We sought to characterize the association between predicted lifetime risk and incident CAC among individuals with low short-term risk. METHODS AND RESULTS: We included 754 Dallas Heart Study participants with serial CAC scans (6.9 years apart) and both low short-term risk and baseline CAC=0. Lifetime risk for cardiovascular disease was estimated according to risk factor burden. Among this group, 365 individuals (48.4%) were at low lifetime risk and 389 (51.6%) at high lifetime risk. High lifetime risk was associated with higher annualized CAC incidence (4.2% versus 2.7%; P < 0.001). Similarly, mean follow-up CAC scores were higher among participants with high lifetime risk (7.8 versus 2.4 Agatston units). After adjustment for age, sex, and race, high lifetime risk remained independently associated with incident CAC (OR 1.60; 95% CI 1.12 to 2.27; P=0.01). When assessing risk factor burden at the follow-up visit, 66.7% of CAC incidence observed in the low lifetime risk group occurred among individuals reclassified to a higher short- or long-term risk category. CONCLUSION: Among individuals with low short-term risk and CAC scores of 0, high lifetime risk is associated with a higher incidence of CAC. These findings highlight the importance of lifetime risk even among individuals with very low short-term risk.

Coronary artery calcification and family history of myocardial infarction in the Dallas heart study.

OBJECTIVES: This study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD). BACKGROUND: FH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for. METHODS: Among 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC. RESULTS: The mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile. CONCLUSIONS: FH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile.

Association of prediabetes by fasting glucose and/or haemoglobin A1c levels with subclinical atherosclerosis and impaired renal function: observations from the Dallas Heart Study.

BACKGROUND: Prediabetes defined by fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) predicts incident diabetes, but their individual and joint associations with micro- and macro-vascular risk remain poorly defined. METHODS: FPG, HbA1c, coronary artery calcium (CAC), carotid wall thickness, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) were measured in adults free from prior diabetes or cardiovascular disease (CVD) in the Dallas Heart Study 2 (DHS-2), a population-based cohort study. Prediabetes was defined by FPG 100-125 mg/dL and/or HbA1c 5.7%-6.4%. Multivariable logistic regression was used to analyse associations of HbA1c and/or FPG in the prediabetes range with subclinical atherosclerosis and renal measures. RESULTS: The study comprised 2340 participants, median age = 49 years; 60% women and 50% black. Those with prediabetes were older (52 vs 48 years), more often men (63% vs 53%), black (53% vs 47%) and obese (58% vs 40%; p < 0.001 for each). Prediabetes was captured by FPG alone (43%), HbA1c alone (30%) or both (27%). Those with prediabetes by HbA1c or FPG versus normal HbA1c/FPG had more CAC [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.5-2.2], higher carotid wall thickness (1.32 vs 1.29 mm, p < 0.001), eGFR < 60 mL/min [OR = 1.6 (95% CI = 1.1-2.4)], UACR > 30 mg/dL [OR = 1.8 (95% CI = 1.2-2.7)] and a higher odds for the composite eGFR + UACR [chronic kidney disease (CKD) ≥ 2] [OR = 1.9 (95% CI = 1.5-2.6)]. After multivariable adjustment, none of these associations remained significant. CONCLUSION: Prediabetes defined by HbA1c and/or FPG criteria is crudely associated with markers of diabetic macro- and micro-vascular disease, but not after statistical adjustment, suggesting the relationships are attributable to other characteristics of the prediabetes population.

Left ventricular contraction patterns in patients with suspected acute coronary syndrome and normal coronary angiograms: a new look at the takotsubo syndrome.

BACKGROUND: Original descriptions of the takotsubo syndrome (TS) included a characteristic left ventricular (LV) contraction pattern, "apical ballooning." Recently, several reports have associated contraction patterns not strictly conforming to the original description with TS. The specifics of the contraction pattern seem to set TS apart from the much larger population of patients with acute coronary syndrome (ACS) but no obstructive coronary artery disease (OCAD). This study was undertaken to compare patients with midventricular and apical dysfunction with those with other LV contraction patterns. HYPOTHESIS: If TS can present with a variety of patterns of LV dysfunction, then both those with and those without the pattern should have the clinical components previously assigned to the syndrome. METHODS: We studied LV contraction patterns in consecutive ACS patients referred for consideration of emergent or urgent percutaneous coronary intervention. RESULTS: Of the 893 patients evaluated in 2008, we excluded 862 on the basis of OCAD, preexisting LV dysfunction, or an obvious alternative cause of symptoms. The remaining 31 (3.5%) also had no OCAD but manifested an LV contraction abnormality. We compared the 15 patients (1.7%) whose ventriculograms met criteria for TS with the 16 patients (1.8%) whose did not. The most common alternative pattern was global hypokinesis, followed by a variety of segmental contraction abnormalities. Patients with the TS pattern were older and had evidence of greater myocardial injury. More than 85% were women. CONCLUSIONS: The TS pattern identifies a distinct subset of ACS patients with a remarkable predominance of postmenopausal women and is therefore fundamental to the definition of this entity. This distinctive facet of the syndrome is likely to be an important clue to its pathogenesis. We did not encounter patients with other patterns of LV dysfunction that could be thought to represent stress-induced cardiomyopathy. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.