Genetic risk of fatty liver disease and mortality in the general population: A Mendelian randomization study.

BACKGROUND & AIMS: Fatty liver disease has been associated with higher all-cause as well as liver-related, ischemic heart disease (IHD)-related and extrahepatic cancer-related mortality in observational epidemiological studies. We tested the hypothesis that fatty liver disease is a causal risk factor for higher mortality. METHODS: We genotyped seven genetic variants known to be associated with fatty liver disease (in PNPLA3, TM6SF2, HSD17B13, MTARC1, MBOAT7, GCKR, and GPAM) in 110 913 individuals from the Danish general population. Hepatic steatosis was measured by hepatic computed tomography in n = 6965. Using a Mendelian randomization framework, we tested whether genetically proxied hepatic steatosis and/or elevated plasma alanine transaminase (ALT) was associated with liver-related mortality. RESULTS: During a median follow-up of 9.5 years, 16 119 individuals died. In observational analyses, baseline elevated plasma ALT was associated with higher all-cause (1.26-fold), liver-related (9-fold), and extrahepatic cancer-related (1.25-fold) mortality. In genetic analyses, the risk alleles in PNPLA3, TM6SF2, and HSD17B13 were individually associated with higher liver-related mortality. The largest effects were seen for the PNPLA3 and TM6SF2 risk alleles, for which homozygous carriers had 3-fold and 6-fold, respectively, higher liver-related mortality than non-carriers. None of the risk alleles, individually or combined into risk scores, were robustly associated with all-cause, IHD-related, or extrahepatic cancer-related mortality. In instrumental variable analyses, genetically proxied hepatic steatosis and higher plasma ALT were associated with liver-related mortality. CONCLUSIONS: Human genetic data support that fatty liver disease is a causal driver of liver-related mortality.

Technical Considerations for Dynamic Myocardial Computed Tomography Perfusion as Part of a Comprehensive Evaluation of Coronary Artery Disease Using Computed Tomography.

Dynamic myocardial computed tomography perfusion (DM-CTP) has good diagnostic accuracy for identifying myocardial ischemia as compared with both invasive and noninvasive reference standards. However, DM-CTP has not yet been implemented in the routine clinical examination of patients with suspected or known coronary artery disease. An important hurdle in the clinical dissemination of the method is the development of the DM-CTP acquisition protocol and image analysis. Therefore, the aim of this article is to provide a review of critical parameters in the design and execution of DM-CTP to optimize each step of the examination and avoid common mistakes. We aim to support potential users in the successful implementation and performance of DM-CTP in daily practice. When performed appropriately, DM-CTP may support clinical decision making. In addition, when combined with coronary computed tomography angiography, it has the potential to shorten the time to diagnosis by providing immediate visualization of both coronary atherosclerosis and its functional relevance using one single modality.

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

BACKGROUND: Women with previous preeclampsia have an increased risk of coronary artery disease later in life. OBJECTIVES: This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population. METHODS: Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA. RESULTS: A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity. CONCLUSIONS: Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

Prevalence of non-alcoholic fatty liver disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis to non-alcoholic steatohepatitis with or without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far there has been scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate-severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD. METHODS: Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen CKD Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density <48 HU was used as a cut-off value for moderate-severe hepatic steatosis. RESULTS: The prevalence of moderate-severe hepatic steatosis was 7.9 and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled dataset from both cohorts, adjusted odds ratios for moderate-severe hepatic steatosis among persons with diabetes, overweight and obesity were 3.1 [95% confidence interval (CI) 1.6-5.9], 14.8 (95% CI 4.6-47.9) and 42.0 (95% CI 12.9-136.6), respectively. CONCLUSIONS: In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate-severe hepatic steatosis as assessed by CT scan.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Left ventricular myocardial crypts: morphological patterns and prognostic implications.

AIMS: Left ventricular (LV) myocardial crypts are considered a subtle marker of hypertrophic cardiomyopathy. However, crypts have also been observed in seemingly healthy individuals and it is unknown whether myocardial crypts are associated with adverse outcome. METHODS AND RESULTS: Myocardial crypts were defined as invaginations traversing >50% of the myocardial wall and assessed using contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. Number of crypts, location, shape, penetrance, and volume were assessed. The endpoint was a composite of major adverse cardiovascular events and defined as death, myocardial infarction, heart failure, or stroke. Cox regression models were adjusted for clinical variables, medical history, electrocardiographic parameters, and cardiac chamber sizes. A total of 1199 LV myocardial crypts were identified in 915 (9.1%) individuals. Seven hundred (6.9%) had one crypt and 215 (2.1%) had multiple crypts. During a median follow-up of 4.0 years (interquartile range 1.5-6.7), major adverse cardiovascular events occurred in 619 individuals. Individuals with one or multiple crypts had a hazard ratio for major adverse cardiovascular events of 1.00 [95% confidence interval (CI): 0.72-1.40; P = 0.98] and 0.90 (95% CI: 0.47-1.75; P = 0.76), respectively, compared with those with no crypts. No specific pattern of crypt location, shape, penetrance, or volume was associated to an increased hazard ratio for major adverse cardiovascular events. CONCLUSION: LV myocardial crypts are frequent in the general population and are not associated with intermediate-term major adverse cardiovascular events.

Left ventricular trabeculation and major adverse cardiovascular events: the Copenhagen General Population Study.

AIMS: Prominent left ventricular trabeculations is a phenotypic trait observed in cardiovascular diseases. In the general population, the extent of left ventricular trabeculations is highly variable, yet it is unknown whether increased trabeculation is associated with adverse outcome. METHODS AND RESULTS: Left ventricular trabeculated mass (g/m2) was measured with contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. The primary endpoint was a composite of major adverse cardiovascular events and defined as death, heart failure, myocardial infarction, or stroke. The secondary endpoints were the individual components of the primary endpoint. Cox regression models were adjusted for clinical parameters, medical history, electrocardiographic parameters, and cardiac chamber sizes. The mean trabeculated mass was 19.1 g/m2 (standard deviation 4.9 g/m2). During a median follow-up of 4.0 years (interquartile range 1.5-6.7), 710 major adverse cardiovascular events occurred in 619 individuals. Individuals with a left ventricular trabeculated mass in the highest quartile had a hazard ratio for major adverse cardiovascular events of 1.64 [95% confidence interval (CI) 1.30-2.08; P < 0.001] compared to those in the lowest quartile. Corresponding hazard ratios were 2.08 (95% CI 1.38-3.14; P < 0.001) for death, 2.63 (95% CI 1.61-4.31; P < 0.001) for heart failure, 1.08 (95% CI 0.56-2.08; P = 0.82) for myocardial infarction, and 1.07 (95% CI 0.72-1.57; P = 0.74) for stroke. CONCLUSION: Increased left ventricular trabeculation is independently associated with an increased rate of major adverse cardiovascular events in the general population.

Pericardial Adipose Tissue Volume Is Independently Associated With Human Immunodeficiency Virus Status and Prior Use of Stavudine, Didanosine, or Indinavir.

BACKGROUND: Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors. METHODS: Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography. RESULTS: A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10-23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, -6 to -25; P = .002) lower pericardial adipose tissue volume. CONCLUSIONS: Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population.

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Prevalence of and Risk Factors for Low Bone Mineral Density Assessed by Quantitative Computed Tomography in People Living With HIV and Uninfected Controls.

BACKGROUND: Low bone mineral density (BMD) has been described in people living with HIV (PLWH). We examined the prevalence of low BMD measured by quantitative computed tomography (QCT), a method that allows 3-dimensional volumetric density measures at the thoracic spine, in well-treated PLWH and uninfected controls and assessed risk factors for reduced BMD. METHODS: Cross-sectional study including 718 PLWH from the Copenhagen Co-Morbidity in HIV infection (COCOMO) study and 718 uninfected controls matched on age and sex from the Copenhagen General Population Study (CGPS). Trabecular BMD was determined by QCT. RESULTS: Median BMD was 144.2 mg/cm in PLWH vs. 146.6 mg/cm in controls (P = 0.580). HIV status was not associated with BMD in univariable or multivariable linear analyses. However, a higher prevalence of very low BMD (T-score ≤ -2.5) was found in PLWH (17.2% vs. 11.0% in controls, P = 0.003). In unadjusted analysis, HIV was associated with very low BMD (odds ratio 1.68 [95% confidence interval: 1.24-2.27], P = 0.001), but this association was not significant after adjusting for age, sex, smoking, alcohol, body mass index, physical activity, and ethnicity. Previous AIDS-defining disease was associated with lower BMD, but no other associations with HIV-specific variables were identified. CONCLUSION: Using QCT, we found a higher prevalence of very low BMD in PLWH than in controls. However, HIV status was not independently associated with BMD indicating that traditional risk factors contribute to the difference in prevalence of very low BMD. Focus on improvement of lifestyle factors, especially in PLWH with previous AIDS-defining disease, may prevent very low BMD in PLWH.

Normal values of aortic dimensions assessed by multidetector computed tomography in the Copenhagen General Population Study.

AIMS: Accurate assessment of aortic dimensions can be achieved using contrast-enhanced computed tomography. The aim of this study was to define normal values and determinants of aortic dimensions throughout multiple key anatomical landmarks of the aorta in healthy individuals from the Copenhagen General Population Study. METHODS AND RESULTS: The study group consisted of 902 healthy subjects selected from 3000 adults undergoing cardiovascular thoracic and abdominal computed tomography-angiography (CTA), where systematic measurements of aortic dimensions were performed retrospectively. Individuals included were without any of the following predefined cardiovascular risk factors: (i) self-reported angina pectoris; (ii) hypertension; (iii) hypercholesterolaemia; (iv) taking cardiovascular prescribed medication including diuretics, statins, or aspirin; (v) overweight (defined as body mass index ≥30 kg/m2); (vi) diabetes mellitus (self-reported or blood glucose >8 mmol/L); and (vii) chronic obstructive pulmonary disease. Maximal aortic diameters were measured at seven aortic regions: sinuses of Valsalva, sinotubular junction, ascending aorta, mid-descending aorta, abdominal aorta at the diaphragm, abdominal aorta at the coeliac trunk, and infrarenal abdominal aorta. Median age was 52 years, and 396 (40%) were men. Men had significantly larger aortic diameters at all levels compared with women (P < 0.001). Multivariable analysis revealed that sex, age, and body surface area were associated with increasing aortic dimensions. CONCLUSION: Normal values of maximal aortic dimensions at key aortic anatomical locations by contrast-enhanced CTA have been defined. Age, sex, and body surface area were significantly associated with these measures at all levels of aorta. Aortic dimensions follow an almost identical pattern throughout the vessel regardless of sex.

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors.

BACKGROUND: Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors. METHODS: In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses. RESULTS: Exposure to thymidine analogs and/or ddI was associated with 21.6 cm larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to thymidine analogs and/or ddI [3.7 cm per year (2.3-5.1)], but not time since discontinuation [-1.1 cm per year (-3.4 to 1.1)], was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension [adjusted odds ratio (aOR) 1.62 (1.13-2.31)], hypercholesterolemia [aOR 1.49 (1.06-2.11)], and low high-density lipoprotein [aOR 1.40 (0.99-1.99)]. CONCLUSIONS: This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.

Risk Prediction of Atrial Fibrillation Based on Electrocardiographic Interatrial Block.

BACKGROUND: The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. METHODS AND RESULTS: Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. CONCLUSIONS: IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.

Computed tomography quantification of emphysema in people living with HIV and uninfected controls.

People living with HIV (PLWH) may be more susceptible to the development of emphysema than uninfected individuals. We assessed prevalence and risk factors for emphysema in PLWH and uninfected controls. Spirometry and chest computed tomography scans were obtained in PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study and in uninfected controls from the Copenhagen General Population Study (CGPS) who were >40 years. Emphysema was quantified using a low attenuation area < -950 Hounsfield units (%LAA-950) and the 15th percentile density index (PD15) and assessed by semi-quantitative visual scales. Of 742 PLWH, 21.2% and 4.7% had emphysema according to the %LAA-950 threshold with cut-offs at 5% and 10%, respectively. Of 470 uninfected controls, these numbers were 24.3% (p=0.23) and 4.0% (p=0.68). HIV was not associated with emphysema (adjusted OR 1.25, 95% CI 0.68-2.36 for %LAA-950 >10%) by PD15 or by visually assessed emphysema. We found no interaction between HIV and cumulative smoking. Breathlessness and sputum production were more common in PLWH with emphysema, and emphysema seemed to be more prevalent in PLWH with airflow limitation. HIV was therefore not independently associated with emphysema, but the clinical impact of emphysema was greater in PLWH than in uninfected controls.

Prediction of clinical outcome by myocardial CT perfusion in patients with low-risk unstable angina pectoris.

The prognostic implications of myocardial computed tomography perfusion (CTP) analyses are unknown. In this sub-study to the CATCH-trial we evaluate the ability of adenosine stress CTP findings to predict mid-term major adverse cardiac events (MACE). In 240 patients with acute-onset chest pain, yet normal electrocardiograms and troponins, a clinically blinded adenosine stress CTP scan was performed in addition to conventional diagnostic evaluation. A reversible perfusion defect (PD) was found in 38 patients (16 %) and during a median follow-up of 19 months (range 12-22 months) 25 patients (10 %) suffered a MACE (cardiac death, non-fatal myocardial infarction and revascularizations). Accuracy for the prediction of MACE expressed as the area under curve (AUC) on receiver-operating characteristic curves was 0.88 (0.83-0.92) for visual assessment of a PD and 0.80 (0.73-0.85) for stress TPR (transmural perfusion ratio). After adjustment for the pretest probability of obstructive coronary artery disease, both detection of a PD and stress TPR were significantly associated with MACE with an adjusted hazard ratio of 39 (95 % confidence interval 11-134), p < 0.0001, for visual interpretation and 0.99 (0.98-0.99) for stress TPR, p < 0.0001. Patients with a PD volume covering >10 % of the LV myocardium had a worse prognosis compared to patients with a PD covering <10 % of the LV myocardium, p = 0.0002. The optimal cut-off value of the myocardial PD extent to predict MACE was 5.3 % of the left ventricle [sensitivity 84 % (64-96), specificity 95 % (91-97)]. Myocardial CT perfusion parameters predict mid-term clinical outcome in patients with recent acute-onset chest pain.

Respiratory influence on left atrial volume calculation with 3D-echocardiography.

BACKGROUND: Left atrial volume (LAV) estimation with 3D echocardiography has been shown to be more accurate than 2D volume calculation. However, little is known about the possible effect of respiratory movements on the accuracy of the measurement. METHODS: 100 consecutive patients admitted with chest pain were examined with 3D echocardiography and LAV was quantified during inspiratory breath hold, expiratory breath hold and during free breathing. RESULTS: Of the 100 patients, only 65 had an echocardiographic window that allowed for 3D echocardiography in the entire respiratory cycle. Mean atrial end diastolic volume was 45.4 ± 14.5 during inspiratory breath hold, 46.4 ± 14.8 during expiratory breath hold and 45.6 ± 14.3 during free respiration. Mean end systolic volume was 17.6 ± 7.8 during inspiratory breath hold, 18.8 ± 8.0 during expiratory breath hold and 18.3 ± 8.0 during free respiration. No significant differences were seen in any of the measured parameters. CONCLUSIONS: The present study adds to the feasibility of 3D LAV quantitation. LAV estimation by 3D echocardiography may be performed during either end-expiratory or end-inspiratory breath-hold without any significant difference in the calculated volume. Also, the LAV estimation may be performed during free breathing.

Long-Term Clinical Impact of Coronary CT Angiography in Patients With Recent Acute-Onset Chest Pain: The Randomized Controlled CATCH Trial.

OBJECTIVES: The aim of the CATCH (CArdiac cT in the treatment of acute CHest pain) trial was to investigate the long-term clinical impact of a coronary computed tomographic angiography (CTA)-guided treatment strategy in patients with recent acute-onset chest pain compared to standard care. BACKGROUND: The prognostic implications of a coronary CTA-guided treatment strategy have not been compared in a randomized fashion to standard care in patients referred for acute-onset chest pain. METHODS: Patients with acute chest pain but normal electrocardiograms and troponin values were randomized to treatment guided by either coronary CTA or standard care (bicycle exercise electrocardiogram or myocardial perfusion imaging). In the coronary CTA-guided group, a functional test was included in cases of nondiagnostic coronary CTA images or coronary stenoses of borderline severity. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), hospitalization for unstable angina pectoris (UAP), late symptom-driven revascularizations, and readmission for chest pain. RESULTS: We randomized 299 patients to coronary CTA-guided strategy and 301 to standard care. After inclusion, 24 patients withdrew their consent. The median (interquartile range) follow-up duration was 18.7 (range 16.8 to 20.1) months. In the coronary CTA-guided group, 30 patients (11%) had a primary endpoint versus 47 patients (16%) in the standard care group (p = 0.04; hazard ratio [HR]: 0.62 [95% confidence interval: 0.40 to 0.98]). A major adverse cardiac event (cardiac death, MI, hospitalization for UAP, and late symptom-driven revascularization) was observed in 5 patients (2 MIs, 3 UAPs) in the coronary CTA-guided group versus 14 patients (1 cardiac death, 7 MIs, 5 UAPs, 1 late symptom-driven revascularization) in the standard care group (p = 0.04; HR: 0.36 [95% CI: 0.16 to 0.95]). Differences in cardiac death and MI (8 vs. 2) were insignificant (p = 0.06). CONCLUSIONS: A coronary CTA-guided treatment strategy appears to improve clinical outcome in patients with recent acute-onset chest pain and normal electrocardiograms and troponin values compared to standard care with a functional test. (Cardiac-CT in the Treatment of Acute Chest Pain [CATCH]; NCT01534000).

P-wave duration and the risk of atrial fibrillation: Results from the Copenhagen ECG Study.

BACKGROUND: Results on the association between P-wave duration and the risk of atrial fibrillation (AF) are conflicting. OBJECTIVE: The purpose of this study was to obtain a detailed description of the relationship between P-wave duration and the risk of AF. METHODS: Using computerized analysis of electrocardiograms from a large primary care population, we evaluated the association between P-wave duration and the risk of AF. Secondary end-points were death from cardiovascular causes and putative ischemic stroke. Data on drug use, comorbidity, and outcomes were collected from administrative registries. RESULTS: A total of 285,933 individuals were included. During median follow-up period of 6.7 years, 9550 developed AF, 9371 died of a cardiovascular cause, and 8980 had a stroke. Compared with the reference group (100-105 ms), individuals with very short (≤89 ms; hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.41-1.81), intermediate (112-119 ms; HR 1.22, 95% CI 1.13-1.31), long (120-129 ms; HR 1.50, 95% CI 1.39-1.62), and very long P-wave duration (≥130 ms; HR 2.06, 95% CI 1.89-2.23) had an increased risk of incident AF. With respect to death from cardiovascular causes, we found an increased risk for very short (≤89 ms; HR 1.20, 95% CI 1.06-1.34), long (120-129 ms; HR 1.11, 95% CI 1.04-1.19), and very long P-wave duration (≥130 ms; HR 1.30, 95% CI 1.21-1.40) compared with the reference group (106-111 ms). Similar but weaker associations were found between P-wave duration and the risk of putative ischemic stroke. CONCLUSION: In a large primary care population we found both short and long P-wave duration to be robustly associated with an increased risk of AF.