Impact of atherosclerosis imaging-quantitative computed tomography on diagnostic certainty, downstream testing, coronary revascularization, and medical therapy: the CERTAIN study.

AIMS: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. METHODS AND RESULTS: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. CONCLUSION: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy.

Impending paradoxical embolism presenting as a pulmonary embolism, transient ischemic attack, and myocardial infarction.

A 25-year-old man presented with complaints of nonpleuritic, substernal chest pain, dyspnea, and decreasing exercise tolerance. His vital signs were normal, with the exception of an oxygen saturation level of 93% while breathing room air. During his assessment, he developed transient left facial droop, left arm and leg weakness, and an ataxic gait, which lasted 15 min then resolved spontaneously. Cardiac enzyme levels were elevated, and an ECG revealed T-wave inversion in leads III, aVF, V1, and V2 with evolving ST-segment elevation in leads V3 through V5. The findings of a CT scan and MRI of the head were negative; a Doppler ultrasound of the right lower extremity revealed a thrombus extending from the common femoral vein to the popliteal vein. Cardiac catheterization revealed no evidence of epicardial coronary artery disease. CT pulmonary angiography revealed bilateral pulmonary emboli. Transesophageal echocardiography (TEE) showed a 4-cm, dumbbell-shaped mass lodged in a patent foramen ovale, confirming the diagnosis of an impending paradoxical embolism. The patient was started on therapy with unfractionated heparin, and his thrombus resolved spontaneously by hospital day 5. An impending paradoxical embolism is rare but should be suspected in anyone presenting with evidence of both venous and arterial emboli. The therapeutic options include anticoagulation, thrombolysis, and surgical embolectomy. We would propose that initial treatment with anticoagulation therapy and following with serial TEEs may be appropriate therapy in an otherwise stable patient, with surgical embolectomy or thrombolysis reserved for the treatment of thrombi that do not resolve with anticoagulation therapy or for patients with clinical deterioration.

Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2.

BACKGROUND: We previously reported in a placebo-controlled study that extended-release niacin slowed the progression of carotid atherosclerosis when added to statin monotherapy. This analysis examines the relationship between glycemic status and the effects of niacin on common carotid intima-media thickness (CIMT) and HDL cholesterol. METHODS: Post-hoc, subgroup analysis of ARBITER 2, a randomized, placebo-controlled trial of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease. The primary analysis was a comparison of the primary endpoint, the change in CIMT, between participants with either normal glycemic status, diabetes mellitus (DM) or the metabolic syndrome (MS). RESULTS: Baseline cardiovascular risk variables were significantly worse in those with abnormal glycemic status, particularly among subjects with MS. Niacin increased HDL-C to a similar degree (approximately 20%) across normals, DM and MS. Placebo-treated patients had the greatest CIMT progression, regardless of glycemic status. The lowest progression rate was observed in niacin treated patients with normal glycemic status. Among all niacin treated subjects, there was a significant linear relationship between change in CIMT and change in HDL-C (r = -0.16; p = 0.05), which was of similar magnitude in subgroups with normal glycemic status (r = -0.23; p = 0.08) and DM (r = -0.22; p = 0.17). In those with MS, there was no relationship between changes in HDL and CIMT, (r = 0.11; p = 0.44), whereas blood glucose was positive correlated to change in CIMT (r = 0.30; p = 0.04). In multivariable linear models controlling for MS characteristics and blood glucose changes, only the change in HDL independently predicted change in CIMT. CONCLUSIONS: During niacin treatment, increases in HDL-C are related to changes in CIMT in the setting of both normal glycemic status and diabetes mellitus.

Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins.

BACKGROUND: Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins; however, the incremental impact of adding niacin to background statin therapy is unknown. METHODS AND RESULTS: This was a double-blind randomized placebo-controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of high-density lipoprotein cholesterol (HDL-C; <45 mg/dL). The primary end point was the change in common carotid intima-media thickness (CIMT) after 1 year. Baseline CIMT (0.884+/-0.234 mm), low-density lipoprotein cholesterol (89+/-20 mg/dL), and HDL-C (40+/-7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90%, and 149 patients (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (0.044+/-0.100 mm; P<0.001) and was unchanged in the niacin group (0.014+/-0.104 mm; P=0.23). Although the overall difference in IMT progression between the niacin and placebo groups was not statistically significant (P=0.08), niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P=0.026). Clinical cardiovascular events occurred in 3 patients treated with niacin (3.8%) and 7 patients treated with placebo (9.6%; P=0.20). CONCLUSIONS: The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.

Real-world application of coronary computed tomography angiography and its potential effect on downstream resource utilization in evaluating angina.

BACKGROUND: Evaluating low-risk outpatients with chest pain is a common clinical problem and poses significant demand on clinical resource utilization. Despite the impressive performance characteristics of coronary multislice computed tomography (MSCT) angiography, its implementation in the diagnostic evaluation of outpatient chest pain and its effect on downstream resource utilization remains undefined. OBJECTIVE: We compared the effect of a strategy that used MSCT with a traditional strategy (pre-MSCT strategy) in which MSCT was not available on clinical downstream resource utilization, defined as the need for further stress testing or cardiac catheterization. METHODS: We retrospectively identified 75 patients without known disease who had undergone MSCT angiography for the primary indication of possible angina. The review of clinical vignettes of these 75 patients and completion of surveys assessing diagnostic strategy by two general cardiologists represented the pre-MSCT diagnostic strategy. Survey responses were compared with the number of cardiac catheterizations and stress tests that actually resulted after MSCT angiography (MSCT strategy). RESULTS: A strategy that used MSCT angiography in the evaluation of patients with possible angina would have significantly reduced the need for further stress testing and cardiac catheterizations (58 vs 11; P < 0.005). Furthermore, this strategy would have resulted in significantly fewer unnecessary cardiac catheterizations (6 vs 23; P < 0.005). CONCLUSIONS: Coronary MSCT angiography can potentially reduce the need for further stress tests or cardiac catheterizations in the evaluation of low- to intermediate-risk patients with possible angina. Prospective studies are needed to validate these findings and to assess the overall cost effectiveness of implementing MSCT early in the outpatient evaluation of angina.

Jugular venous pulse: window into the right heart.

Although physicians began associating conspicuous neck veins with heart disease almost three centuries ago, the jugular venous pulse remains an often ignored component of the physical examination. Many physicians have not invested in the necessary understanding of the technique, and there is a misconception that its examination is difficult and of limited clinical value. When performed properly, evaluation of the jugular venous pulse can be extremely useful in distinguishing the cause of dyspnea and edema. The normal jugular venous pulse is reviewed, and pulse wave abnormalities are described, including ways in which they can provide clues to the diagnosis of certain disease states, ranging from pericardial disease to conduction disturbances. The jugular venous pulse provides a window into the right heart and an occasional glimpse of left heart hemodynamics. By peering through this window, clinicians can gain valuable information in the diagnostic evaluation of the cardiovascular patient.

How should we measure medication adherence in clinical trials and practice?

OBJECTIVE: To determine if simple adherence measures, such as twenty-four hour recall and refill history, are accurate for routine use, compared to more time-consuming measures such as pill counts. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Walter Reed Army Medical Center, a tertiary medical center in Washington. PATIENTS: Men and women >30 years old with known coronary heart disease and taking a statin medication. INTERVENTION: Clinical pharmacists met with patients for adherence assessments. MAIN OUTCOME MEASURES: Adherence was measured by pill counts, twenty-four hour recall by patient, and refill history per computer record. Temporal changes in these adherence measures were assessed using general linear models for repeated measures. RESULTS: Adherence was consistently greater for the experimental agent than for the statin therapy (n = 148). Mean pill count adherence for statin drug was 78.7 +/- 25.2% compared to 93.5 +/- 11.6% (P < 0.001) for the study agent. Refill history and twenty-four hour recall inaccurately measured adherence when compared to pill counts. Adherence, as determined by pill count, for both experimental (P = 0.029) and statin therapy (P = 0.015) showed significant variability across time in general linear models. Neither refill history nor twenty-four hour recall was sensitive to temporal changes. CONCLUSIONS: Twenty-four hour recall and refill history inaccurately measure medication adherence for both clinical trial and clinical practice pharmacotherapies. Further, these measures are insensitive to changes in adherence. For a single or multiple assessments across time, pill count more accurately measures medication adherence. Pill count should be the standard for monitoring medication adherence for both clinical trials and clinical practice.

The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3.

OBJECTIVE: The ARBITER 2 trial showed that extended-release niacin (ERN) when added to statin monotherapy slowed the progression of carotid atherosclerosis over 12 months. Whether longer treatment with ERN would have a greater effect on carotid intima-media thickness (CIMT) is unknown. RESEARCH DESIGN AND METHODS: We examined the long-term effects of ERN on high density lipoprotein (HDL-C) cholesterol and CIMT during 12-24 months treatment with ERN in ARBITER 2 participants who were either continued or were crossed over (from placebo) to ERN 1000 mg daily. MAIN OUTCOME MEASURES: Among 149 subjects completing ARBITER 2, 130 (88%) enrolled in ARBITER 3. The prespecified primary endpoints were the within-group change in CIMT and HDL-C in patients receiving placebo for 12 months (n = 71), ERN for 12 months (comprised of subjects from ERN treatment during ARBITER 2 (n = 78) and those crossed over to ERN from placebo after ARBITER 2 (n = 47)), and ERN for 24 months spanning ARBITER 2 and 3 (n = 57). Five subjects discontinued the study due to flushing side effects. The study was completed by 104 subjects (47 crossed over from placebo; 57 with ERN continued from ARBITER 2). RESULTS: HDL-C increased in the ERN group from 39.5 +/- 6.7 to 48.6 +/- 13.3 mg/dl (p < 0.001) along with modest reductions in LDL-C and TG. Among 125 participants treated with ERN for 12 months, there was a net regression of CIMT of -0.027 +/- 0.011 mm (p < 0.001 vs. placebo). Among 57 participants treated with ERN for 24 months, there was additional significant regression of CIMT of -0.041 +/- 0.021 mm (p = 0.001 vs. placebo). Controlling for changes in LDL and triglycerides, only changes in HDL-C were independently associated with regression of CIMT (beta = -0.25; p = 0.001). CONCLUSION: When added to statin therapy, ERN significantly increases HDL-C and induces atherosclerosis regression measured by CIMT over 24 months. Limitations to this study include its open-label design and the inability to relate CIMT effects to clinical outcomes.