Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Primary carnitine deficiency is a life-long disease.

Primary carnitine deficiency is a rare autosomal recessive disease associated with acute hypoketotic hypoglycaemia, cardiomyopathy and sudden cardiac death. Effective treatment with carnitine supplementation is available. An 18 months old boy, who presented with cardiomyopathy was diagnosed with primary carnitine deficiency, and carnitine supplementation resulted in a full recovery. At age 13 years, he discontinued his medication and at 20 years, he discontinued clinical monitoring. Nine years later, age 29, he presented with heart failure and atrial fibrillation and was admitted to an intensive care unit, where he was treated with furosemide, enoximone and intravenous carnitine supplementation, this lead to improved cardiac function within 2 weeks, and with continued oral carnitine supplements, his left ventricular ejection fraction normalised. The last 8 years were uneventful and he continued to attend his regular follow-up visits at a specialised metabolic outpatient clinic. We report recurrent reversible severe heart failure in a patient with primary carnitine deficiency; it was directly related to non-compliance to carnitine supplementation (and monitoring). This case report emphasises first, the importance of continued monitoring of metabolic disease patients, second, the potential reversibility of cardiomyopathy in an adult patient, and third, the potential risks in the period of transition from the paediatric to adult care. This is an age where young adults desire to be healthy and ignore the need for ongoing medical treatment, even as simple as oral suppletion. Before they reach this age, adequate disease insight and self-management of the disease should be promoted.

Left atrial diverticula: Innocent bystanders or wolves in sheep's clothing?

INTRODUCTION: The finding of left atria diverticula (LAD) on cardiac computed tomography images obtained from patients with atrial fibrillation (AF) referred for pulmonary vein isolation is not uncommon. Prior studies reporting on LAD do not always provide definitions of LAD resulting in confusion with other anatomical structures such as left atrial accessory appendages (LAAA) and atrial aneurysms. The aim of this review is to identify an accurate definition of LAD and to describe distinctive properties between LAD and other left atrial structures, such as LAAA and aneurysms. Also, the relation between LAD and development of atrial tachyarrhythmias is discussed. METHODS: PubMed was searched for studies reporting on atrial aneurysms, left atrial diverticula, left atrial accessory appendages and atrial congenital aneurysms, resulting in 36 papers. RESULTS: LAD can be distinguished from LAAA by taking into account embryologic origins of the left atrium and their locations, resulting in the following definitions: (a) LAAA are contractile, trabeculated structures with circumscriptive ostia and narrow necks, originating from the primitive atria, (b) LAD are contractile, sac like structures with either smooth or trabeculated inner surfaces, circumscriptive ostia, narrow necks, and variable morphologies, originating from the embryologic common pulmonary vein, that incorporates into the LA, and (c) atrial aneurysms are non-contractile structures with wide necks and sac like bodies. There are no differences in prevalences of LAD between patients with sinus rhythm and AF. CONCLUSION: The pathophysiology of LAD is not yet fully understood. It is unlikely, that LAD are related to the development of atrial tachycardia's and AF by either being a source of ectopic activity or being part of an arrhythmogenic substrate. No differences in LAD prevalences between patients with sinus rhythm and AF have been found. Thus, it is unlikely that LAD could potentially be wolves in sheep's clothing.

Improvement of Cardiac Function After Roux-en-Y Gastric Bypass in Morbidly Obese Patients Without Cardiac History Measured by Cardiac MRI.

PURPOSE: Metabolic syndrome in patients with morbid obesity causes a higher cardiovascular morbidity, eventually leading to left ventricular hypertrophy and decreased left ventricular ejection fraction (LVEF). Roux-en-Y gastric bypass (RYGB) is considered the gold standard modality for treatment of morbid obesity and might even lead to improved cardiac function. Our objective is to investigate whether cardiac function in patients with morbid obesity improves after RYGB. MATERIALS AND METHODS: In this single center pilot study, 15 patients with an uneventful cardiac history who underwent RYGB were included from May 2015 to March 2016. Cardiac function was measured by cardiac magnetic resonance imaging (CMRI), performed preoperatively and 3, 6, and 12 months postoperative. LVEF and myocardial mass and cardiac output were measured. RESULTS: A total of 13 patients without decreased LVEF preoperative completed follow-up (mean age 37, 48.0 ± 8.8). There was a significant decrease of cardiac output 12 months postoperative (8.3 ± 1.8 preoperative vs. 6.8 ± 1.8 after 12 months, P = 0.001). Average myocardial mass declined by 15.2% (P < 0.001). After correction for body surface area (BSA), this appeared to be non-significant (P = 0.36). There was a significant improvement of LVEF/BSA at 6 and 12 months postoperative (26.2 ± 4.1 preoperative vs. 28.4 ± 3.4 and 29.2 ± 3.6 respectively, both P = 0.002). Additionally, there was a significant improvement of stroke volume/BSA 12 months after surgery (45.8 ± 8.0 vs. 51.9 ± 10.7, P = 0.033). CONCLUSION: RYGB in patients with morbid obesity with uneventful history of cardiac disease leads to improvement of cardiac function.

Impact of machine-learning CT-derived fractional flow reserve for the diagnosis and management of coronary artery disease in the randomized CRESCENT trials.

OBJECTIVE: To determine the potential impact of on-site CT-derived fractional flow reserve (CT-FFR) on the diagnostic efficiency and effectiveness of coronary CT angiography (CCTA) in patients with obstructive coronary artery disease (CAD) on CCTA. METHODS: This observational cohort study included patients with suspected CAD who had been randomized to cardiac CT in the CRESCENT I and II trials. On-site CT-FFR was blindly performed in all patients with at least one ≥ 50% stenosis on CCTA and no exclusion criteria for CT-FFR. We retrospectively assessed the effect of adding CT-FFR to the CT protocol in patients with a stenosis ≥ 50% on CCTA in terms of diagnostic effectiveness, i.e., the number of additional tests required to determine the final diagnosis, reclassification of the initial management strategy, and invasive coronary angiography (ICA) efficiency, i.e., ICA rate without ≥ 50% CAD. RESULTS: Fifty-three patients out of the 372 patients (14%) had at least one ≥ 50% stenosis on CCTA of whom 42/53 patients (79%) had no exclusion criteria for CT-FFR. CT-FFR showed a hemodynamically significant stenosis (≤ 0.80) in 27/53 patients (51%). The availability of CT-FFR would have reduced the number of patients requiring additional testing by 57%-points compared with CCTA alone (37/53 vs. 7/53, p < 0.001). The initial management strategy would have changed for 30 patients (57%, p < 0.001). Reserving ICA for patients with a CT-FFR ≤ 0.80 would have reduced the number of ICA following CCTA by 13%-points (p = 0.016). CONCLUSION: Implementation of on-site CT-FFR may change management and improve diagnostic efficiency and effectiveness in patients with obstructive CAD on CCTA. KEY POINTS: • The availability of on-site CT-FFR in the diagnostic evaluation of patients with obstructive CAD on CCTA would have significantly reduced the number of patients requiring additional testing compared with CCTA alone. • The implementation of on-site CT-FFR would have changed the initial management strategy significantly in the patients with obstructive CAD on CCTA. • Restricting ICA to patients with a positive CT-FFR would have significantly reduced the ICA rate in patients with obstructive CAD on CCTA.

Iodixanol versus Iopromide at Coronary CT Angiography: Lumen Opacification and Effect on Heart Rhythm-the Randomized IsoCOR Trial.

Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial. Between November 2015 and August 2016, 306 patients (167 [55%] women) at least 18 years old (weight range, 50-125 kg), were prospectively randomized to receive iso-osmolar iodixanol 270 or low-osmolar iopromide 300 contrast media. All coronary segments were assessed for intraluminal opacification and image quality and were compared by using the Student t test. Heart rate, arrhythmia, patient discomfort, and adverse events also were monitored. Results Mean measured coronary attenuation values ± standard deviation were comparable between the iodixanol 270 and iopromide 300 contrast media groups (469 HU ± 167 vs 447 HU ± 166, respectively [P = .241]; 95% confidence interval: -15.1, 60.0), including those from subanalyses. Adjusted for the lower iodine concentration, the mean iodixanol 270 bolus was larger compared with that of iopromide 300 (76.8 mL ± 11.6 vs 69.7 mL ± 10.8, respectively; P < .001). The higher injection rate was associated with higher pressure (777 kPa ± 308 vs 630 kPa ± 252, respectively; P < .001). Although in the iodixanol 270 group patients experienced less heat discomfort (72% vs 86%, respectively; P < .001), no differences in heart rate or rhythm were observed. Conclusion If injected at comparable iodine delivery rates, the iso-osmolar contrast medium iodixanol 270 is not inferior to low-osmolar contrast medium iopromide 300 for assessment of coronary opacification. Iodixanol 270 was associated with less heat discomfort, but did not affect heart rate differently compared with iopromide 300. © RSNA, 2017 Online supplemental material is available for this article.

Age-Related Effects of Bariatric Surgery on Early Atherosclerosis and Cardiovascular Risk Reduction.

BACKGROUND: Carotid intima-media thickness (CIMT) is increasingly used as a prognostic indicator for early atherosclerosis and the development of cardiovascular disease. The objective of this study is to assess the exact effects of bariatric surgery on CIMT reduction in different age groups. METHODS: CIMT was measured just proximal to the bifurcation of the carotid artery in 166 patients with mean body mass index of 43.4 kg/m2 before and at 6 and 12 months after bariatric surgery. Preoperative CIMT and Framingham Risk Score (FRS) were compared to measurements at 6 and 12 months, postoperatively. Impact of age on CIMT change and cardiovascular risk reduction was analyzed. RESULTS: Median follow-up was 12 months; 12% were lost to follow-up. Mean CIMT values at 12 months after bariatric surgery were significantly lower compared to baseline (0.619 vs. 0.587 mm, p = 0.005 in women and 0.675 vs. 0.622 mm, p = 0.037 in men, respectively), and these effects were statistically significant in all age groups. The mean reduction of CIMT for patients < 50 years at 12 months was 0.043 mm (- 7.0%), while CIMT was reduced with 0.013 mm for patients ≥ 50 years (- 1.9%, p = 0.022). At 12 months after bariatric surgery, FRS had decreased with 52% in patients < 50 years as compared with 35% in patients ≥ 50 years (p = 0.025). CONCLUSIONS: Bariatric surgery resulted in a significant CIMT decrease in patients with morbid obesity in all evaluated age categories. These beneficial effects of bariatric surgery were more pronounced in younger patients, while cardiovascular risk reduction by bariatric surgery appeared inferior in patients of 50 years and older.

Comprehensive Cardiac CT With Myocardial Perfusion Imaging Versus Functional Testing in Suspected Coronary Artery Disease: The Multicenter, Randomized CRESCENT-II Trial.

OBJECTIVES: This study sought to assess the effectiveness, efficiency, and safety of a tiered, comprehensive cardiac computed tomography (CT) protocol in comparison with functional testing. BACKGROUND: Although CT angiography accurately rules out coronary artery disease (CAD), incorporation of CT myocardial perfusion imaging as part of a tiered diagnostic approach could improve the clinical value and efficiency of cardiac CT in the diagnostic work-up of patients with angina pectoris. METHODS: Between July 2013 and November 2015, 268 patients (mean age 58 years; 49% female) with stable angina (mean pre-test probability 54%) were prospectively randomized between cardiac CT and standard guideline-directed functional testing (95% exercise electrocardiography). The tiered cardiac CT protocol included a calcium scan, followed by CT angiography if calcium was detected. Patients with ≥50% stenosis on CT angiography underwent CT myocardial perfusion imaging. RESULTS: By 6 months, the primary endpoint, the rate of invasive coronary angiograms without a European Society of Cardiology class I indication for revascularization, was lower in the CT group than in the functional testing group (2 of 130 [1.5%] vs. 10 of 138 [7.2%]; p = 0.035), whereas the proportion of invasive angiograms with a revascularization indication was higher (88% vs. 50%; p = 0.017). The median duration until the final diagnosis was 0 (0 of 0) days in the CT group and 0 (0 of 17) in the functional testing group (p < 0.001). Overall, 13% of patients randomized to CT required further testing, compared with 37% in the functional testing group (p < 0.001). The adverse event rate was similar (3% vs. 3%; p = 1.000), although the median cumulative radiation dose was higher for the CT group (3.1 mSv [interquartile range: 1.6 to 7.8] vs. 0 mSv [interquartile range: 0.0 to 7.1]; p < 0.001). CONCLUSIONS: In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484).

Correction to: Age-Related Effects of Bariatric Surgery on Early Atherosclerosis and Cardiovascular Risk Reduction.

Frederik H. W. Jonker and Vera A. A. van Houten contributed equally to this work.

Sex Differences in the Performance of Cardiac Computed Tomography Compared With Functional Testing in Evaluating Stable Chest Pain: Subanalysis of the Multicenter, Randomized CRESCENT Trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease).

BACKGROUND: Cardiac computed tomography (CT) represents an alternative diagnostic strategy for women with suspected coronary artery disease, with potential benefits in terms of effectiveness and cost-efficiency. METHODS AND RESULTS: The CRESCENT trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease) prospectively randomized 350 patients with stable angina (55% women; aged 55±10 years), mostly with an intermediate coronary artery disease probability, between cardiac CT and functional testing. The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. Sex differences were studied as a prespecified subanalysis. Enrolled women presented more frequently with atypical chest pain and had a lower pretest probability of coronary artery disease compared with men. Independently of these differences, cardiac CT led in both sexes to a fast final diagnosis when compared with functional testing, although the effect was larger in women (P interaction=0.01). The reduced need for further testing after CT, compared with functional testing, was most evident in women (P interaction=0.009). However, no sex interaction was observed with respect to changes in angina and quality of life, cumulative diagnostic costs, and applied radiation dose (all P interactions≥0.097). CONCLUSIONS: Cardiac CT is more efficient in women than in men in terms of time to reach the final diagnosis and downstream testing. However, overall clinical outcome showed no significant difference between women and men after 1 year. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01393028.

Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial.

AIMS: To compare the effectiveness and safety of a cardiac computed tomography (CT) algorithm with functional testing in patients with symptoms suggestive of coronary artery disease (CAD). METHODS AND RESULTS: Between April 2011 and July 2013, 350 patients with stable angina, referred to the outpatient clinic of four Dutch hospitals, were prospectively randomized between cardiac CT and functional testing (2 : 1 ratio). The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. By 1 year, fewer patients randomized to cardiac CT reported anginal complaints (P = 0.012). The cumulative radiation dose was slightly higher in the CT group (6.6 ± 8.7 vs. 6.1 ± 9.3 mSv; P < 0.0001). After 1.2 years, event-free survival was 96.7% for patients randomized to CT and 89.8% for patients randomized to functional testing (P = 0.011). After CT, the final diagnosis was established sooner (P < 0.0001), and additional downstream testing was required less frequently (25 vs. 53%, P < 0.0001), resulting in lower cumulative diagnostic costs (€369 vs. €440; P < 0.0001). CONCLUSION: For patients with suspected stable CAD, a tiered cardiac CT protocol offers an effective and safe alternative to functional testing. Incorporating the calcium scan into the diagnostic workup was safe and lowered diagnostic expenses and radiation exposure.

Evaluation of lecithinized human recombinant super oxide dismutase as cardioprotectant in anthracycline-treated breast cancer patients.

AIM: Anthracycline-induced cardiotoxicity is (partly) mediated by free radical overload. A randomized study was performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) protects against anthracycline-induced cardiotoxicity as measured by changes in echo, electrocardiography and an array of biomarkers. METHOD AND RESULTS: Eighty female, chemotherapy-naïve breast cancer patients (median age 49, range 24-67 years) scheduled for four or five courses of adjuvant 3 weekly doxorubicin plus cyclophosphamide (AC) chemotherapy, were randomly assigned to receive 80 mg PC-SOD (human recombinant SOD bound to lecithin) or placebo, administered intravenously (i.v.) immediately prior to each AC course. The primary end point was protection against cardiac damage evaluated using echocardiography, QT assessments and a set of biochemical markers for myocardial function, oxidative stress and inflammation. Assessments were performed before and during each course of chemotherapy, and at 1, 4 and 9 months after completion of the chemotherapy regimen. In all patients cardiac effects such as increases in NT-proBNP concentration and prolongation of the QTc interval were noticed. There were no differences between the PC-SOD and placebo-treated patients in systolic or diastolic cardiac function or for any other of the biomarkers used to assess the cardiac effects of anthracyclines. CONCLUSION: PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.

Cardiac tamponade due to a ruptured aneurysm of the sinus of valsalva.

BACKGROUND AND AIM: A sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly. Rupture of a SVA often causes hemodynamic instability due to intracardiac shunting or cardiac tamponade, therefore immediate diagnosis and urgent treatment are required. METHODS: We report an 18-year-old female with cardiac tamponade due to rupture of a localized aneurysm of the right coronary sinus of Valsalva. No other congenital or acquired cardiac anomalies were found. Neurological observation precluded urgent surgery with heparinization and extracorporeal circulation. RESULTS: Semi-urgently the SVA was successfully resected. CONCLUSIONS: Semi-urgent surgery for a ruptured aneurysm of the Sinus of Valsalva was successful. In selected cases off pump surgery can be contemplated.