Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

High-quality annotations for deep learning enabled plaque analysis in SCAPIS cardiac computed tomography angiography.

Background: Plaque analysis with coronary computed tomography angiography (CCTA) is a promising tool to identify high risk of future coronary events. The analysis process is time-consuming, and requires highly trained readers. Deep learning models have proved to excel at similar tasks, however, training these models requires large sets of expert-annotated training data. The aims of this study were to generate a large, high-quality annotated CCTA dataset derived from Swedish CArdioPulmonary BioImage Study (SCAPIS), report the reproducibility of the annotation core lab and describe the plaque characteristics and their association with established risk factors. Methods and results: The coronary artery tree was manually segmented using semi-automatic software by four primary and one senior secondary reader. A randomly selected sample of 469 subjects, all with coronary plaques and stratified for cardiovascular risk using the Systematic Coronary Risk Evaluation (SCORE), were analyzed. The reproducibility study (n = 78) showed an agreement for plaque detection of 0.91 (0.84-0.97). The mean percentage difference for plaque volumes was -0.6% the mean absolute percentage difference 19.4% (CV 13.7%, ICC 0.94). There was a positive correlation between SCORE and total plaque volume (rho = 0.30, p < 0.001) and total low attenuation plaque volume (rho = 0.29, p < 0.001). Conclusions: We have generated a CCTA dataset with high-quality plaque annotations showing good reproducibility and an expected correlation between plaque features and cardiovascular risk. The stratified data sampling has enriched high-risk plaques making the data well suited as training, validation and test data for a fully automatic analysis tool based on deep learning.

Calcium Load in the Aortic Valve, Aortic Root, and Left Ventricular Outflow Tract and the Risk for a Periprocedural Stroke.

Background: Periprocedural stroke during transcatheter aortic valve implantation is a rare but devastating complication. The calcified aortic valve is the most likely source of the emboli in a periprocedural stroke. The total load and distribution of calcium in the leaflets, aortic root, and left ventricular outflow tract varies from patient to patient. Consequently, there could be patterns of calcification that are associated with a higher risk of stroke. This study aimed to explore whether the pattern of calcification in the left ventricular outflow tract, annulus, aortic valve, and ascending aorta can be used to predict a periprocedural stroke. Methods: Among the 3282 consecutive patients who received a transcatheter aortic valve implantation in the native valve in Sweden from 2014 to 2018, we identified 52 who had a periprocedural stroke. From the same cohort, a control group of 52 patients was constructed by propensity score matching. Both groups had one missing cardiac computed tomography, and 51 stroke and 51 control patients were blindly reviewed by an experienced radiologist. Results: The groups were well balanced in terms of demographics and procedural data. Of the 39 metrics created to describe calcium pattern, only one differed between the groups. The length of calcium protruding above the annulus was 10.6 mm (interquartile range 7-13.6) for patients without stroke and 8 mm (interquartile range 3-10) for stroke patients. Conclusions: This study could not find any pattern of calcification that predisposes for a periprocedural stroke.

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

BACKGROUND: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. METHODS: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. RESULTS: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. CONCLUSIONS: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

Unrecognized myocardial infarction assessed by cardiac magnetic resonance imaging is associated with adverse long-term prognosis.

BACKGROUND: Unrecognized myocardial infarctions (UMIs) are common. The study is an extension of a previous study, aiming to investigate the long-term (>5 year) prognostic implication of late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) detected UMI in patients with suspected stable coronary artery disease (CAD) without previously diagnosed myocardial infarction (MI). METHODS: In 235 patients with suspected stable CAD without previous MI, LGE-CMR imaging and coronary angiography were performed. LGE with a subendocardial component detectable in more than one imaging plane was required to indicate UMI. The stenosis grade of the coronary arteries was determined, including in the artery supplying an infarcted area. Stenosis ≥70% stenosis was considered significant. Patients were followed for 5.4 years in mean regarding a composite endpoint of cardiovascular death, MI, hospitalization due to heart failure, stable or unstable angina. RESULTS: UMI were present in 58 of 235 patients (25%). Thirty-nine of the UMIs were located downstream of a significant coronary stenosis. During the follow-up 40 patients (17.0%) reached the composite endpoint. Of patients with UMI, 34.5% (20/58) reached the primary endpoint compared to 11.3% (20/177) of patients with no UMI (HR 3.7, 95% CI 2.0-6.9, p<0.001). The association between UMI and outcome remained (HR 2.3, 95% CI 1.2-4.4, p = 0.012) after adjustments for age, gender, extent of CAD and all other variables univariate associated with outcome. Sixteen (41%) of the patients with an UMI downstream of a significant stenosis reached the endpoint compared to four (21%) patients with UMI and no relation to a significant stenosis (HR 2.4, 95% CI 0.8-7.2, p = 0.12). CONCLUSION: The presence of UMI was independently associated with an increased risk of cardiovascular events during long-term follow up.

Radiation dose distribution in coronary arteries in breast cancer radiotherapy.

BACKGROUND: Women irradiated for left-sided breast cancer (BC) have an increased risk of coronary artery disease compared to women with right-sided BC. We describe the distribution of radiation dose in segments of coronary arteries in women receiving adjuvant radiotherapy (RT) for left- or right-sided BC. MATERIAL AND METHODS: Fifteen women with BC, seven left-sided and eight right-sided, who had received three-dimensional conformal radiotherapy (3DCRT), constituted the study base. The heart and the segments of the coronary arteries were defined as separate organs at risk (OAR), and the mean and maximum radiation doses were calculated for each OAR. RESULTS: In women with left-sided BC, irrespective of if regional lymph node RT was given or not, maximum dose in mid and distal left anterior descending artery (mdLAD) was approximately 50 Gy in 6/7 patients, whereas women with right-sided BC mainly received low doses of radiation. In women with left-sided BC, 6/7 patients had substantially higher mean dose to the distal LAD than to the heart, ranging from 30 to 55 Gy and 3 to13 Gy, respectively. CONCLUSION: We found a pronounced difference of radiation dose distribution in the coronary arteries between women with left- and right-sided BC. Women with left-sided BC had almost full treatment dose in parts of mdLAD, regardless of if regional lymph node irradiation was given or not, while women with right-sided BC mainly received low doses to the coronary arteries.

Unrecognized myocardial infarctions detected by cardiac magnetic resonance imaging are associated with cardiac troponin I levels.

BACKGROUND: Both unrecognized myocardial infarction (UMI) and elevated levels of biomarkers are common in patients with stable coronary artery disease (CAD). The objective of this study was to determine the association between levels of cardiac biomarkers, UMI and extent of CAD in patients with stable CAD. METHODS: A total of 235 patients (median age: 65years; 34% women) with stable CAD without previously known myocardial infarction were examined with late gadolinium enhancement cardiovascular magnetic resonance imaging and coronary angiography. Blood samples were drawn at enrolment and high sensitivity cardiac troponin I (cTnI), NT-proBNP and Galectin-3 were analyzed. RESULTS: UMI was detected in 58 patients (25%). The median levels of cTnI, NT-proBNP and Galectin-3 were significantly higher in patients with UMI compared to those without, (p<0.001, p=0.006 and p=0.033, respectively). After adjustment for cardiovascular risk factors, left ventricular ejection fraction and renal function, cTnI remained independently associated with the presence of UMI (p=0.031) and the extent of CAD (p=0.047). Neither NT-proBNP, nor Galectin-3, was independently associated with UMI or extent of CAD. CONCLUSIONS: The independent association between levels of cTnI and UMI indicates a common pathophysiological pathway for the cTnI elevation and development of UMI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01257282).

Unrecognized Myocardial Infarction Assessed by Cardiac Magnetic Resonance Imaging--Prognostic Implications.

BACKGROUND: Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD. METHODS AND FINDINGS: In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade ≥70%. In an age- and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1-7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery. CONCLUSIONS: The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR. TRIAL REGISTRATION: ClinicalTrials.gov NTC01257282.

Unrecognized myocardial infarctions assessed by cardiovascular magnetic resonance are associated with the severity of the stenosis in the supplying coronary artery.

BACKGROUND: A previous study has shown an increased prevalence of late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) detected unrecognized myocardial infarction (UMI) with increasing extent and severity of coronary artery disease. However, the coronary artery disease was evaluated on a patient level assuming normal coronary anatomy. Therefore, the aims of the present study were to investigate the prevalence of UMI identified by LGE CMR imaging in patients with stable angina pectoris and no known previous myocardial infarction; and to investigate whether presence of UMI is associated with stenotic lesions in the coronary artery supplying the segment of the myocardium in which the UMI is located, using coronary angiography to determine the individual coronary anatomy in each patient. METHODS: In this prospective multicenter study, we included patients with stable angina pectoris and without prior myocardial infarction, scheduled for coronary angiography. A LGE CMR examination was performed prior to the coronary angiography. The study cohort consisted of 235 patients (80 women, 155 men) with a mean age of 64.8 years. RESULTS: UMIs were found in 25% of patients. There was a strong association between stenotic lesions (≥70% stenosis) in a coronary artery and the presence of an UMI in the myocardial segments supplied by the stenotic artery; it was significantly more likely to have an UMI downstream a stenosis ≥ 70% as compared to < 70% (OR 5.1, CI 3.1-8.3, p < 0.0001). 56% of the UMIs were located in the inferior and infero-lateral myocardial segments, despite predominance for stenotic lesions in the left anterior descending artery. CONCLUSION: UMI is common in patients with stable angina and the results indicate that the majority of the UMIs are of ischemic origin due to severe coronary atherosclerosis. In contrast to what is seen in recognized myocardial infarctions, UMIs are predominately located in the inferior and infero-lateral myocardial segments. TRIAL REGISTRATION: The PUMI study is registered at ClinicalTrials.gov (NCT01257282).

Cardiac Imaging to Evaluate Left Ventricular Diastolic Function.

Left ventricular diastolic dysfunction in clinical practice is generally diagnosed by imaging. Recognition of heart failure with preserved ejection fraction has increased interest in the detection and evaluation of this condition and prompted an improved understanding of the strengths and weaknesses of different imaging modalities for evaluating diastolic dysfunction. This review briefly provides the pathophysiological background for current clinical and experimental imaging parameters of diastolic dysfunction, discusses the merits of echocardiography relative to other imaging modalities in diagnosing and grading diastolic dysfunction, summarizes lessons from clinical trials that used parameters of diastolic function as an inclusion criterion or endpoint, and indicates current areas of research.

Distribution of coronary artery stenosis after radiation for breast cancer.

PURPOSE: To study distribution of coronary artery stenosis among patients with breast cancer (BC) and to assess correlation between radiotherapy (RT) and location of stenosis. PATIENTS AND METHODS: A Swedish BC cohort diagnosed from 1970 to 2003 was linked to registers of coronary angiography from 1990 to 2004, which yielded 199 patients. Stenoses of the coronary arteries were graded from 0 to 5, where 0 indicated a normal vessel and 5 indicated occlusion. Two hotspot areas for radiation were defined: proximal right coronary artery (prox RCA), mid and distal left anterior descending artery and distal diagonal (mdLAD + dD). RT regimens were categorized as high or low risk of irradiating the hotspot areas. Left breast/chest wall was considered high risk for mdLAD + dD; left internal mammary chain (IMC), high risk for prox RCA and mdLAD + dD from 1970 to 1995 and thereafter solely for mdLAD + dD; and right IMC, high risk for prox RCA. Other RT targets and no RT were considered low risk. Results were expressed in odds ratios (ORs) and 95% CIs. RESULTS: For irradiated left- versus right-sided BC, the OR for grade 3 to 5 stenosis in mdLAD + dD was 4.38 (95% CI, 1.64 to 11.7), and for grade 4 to 5 stenosis, the OR was 7.22 (95% CI, 1.64 to 31.8). For high-risk RT versus low-risk or no RT, the OR for grade 3 to 5 stenosis in hotspot areas was 1.90 (95% CI, 1.11 to 3.24). CONCLUSION: An increase of stenosis in mdLAD + dD in irradiated left-sided BC and an association between high-risk RT and stenosis in hotspot areas for radiation indicate a direct link between radiation and location of coronary stenoses.

Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study.

BACKGROUND: Morbidly obese patients show impaired pulmonary function during anesthesia and paralysis, partly due to formation of atelectasis. This study analyzed the effect of general anesthesia and three different ventilatory strategies to reduce the amount of atelectasis and improve respiratory function. METHODS: Thirty patients (body mass index 45 +/- 4 kg/m) scheduled for gastric bypass surgery were prospectively randomized into three groups: (1) positive end-expiratory pressure of 10 cm H2O (PEEP), (2) a recruitment maneuver with 55 cm H2O for 10 s followed by zero end-expiratory pressure, (3) a recruitment maneuver followed by PEEP. Transverse lung computerized tomography scans and blood gas analysis were recorded: awake, 5 min after induction of anesthesia and paralysis at zero end-expiratory pressure, and 5 min and 20 min after intervention. In addition, spiral computerized tomography scans were performed at two occasions in 23 of the patients. RESULTS: After induction of anesthesia, atelectasis increased from 1 +/- 0.5% to 11 +/- 6% of total lung volume (P < 0.0001). End-expiratory lung volume decreased from 1,387 +/- 581 ml to 697 +/- 157 ml (P = 0.0014). A recruitment maneuver + PEEP reduced atelectasis to 3 +/- 4% (P = 0.0002), increased end-expiratory lung volume and increased Pao2/Fio2 from 266 +/- 70 mmHg to 412 +/- 99 mmHg (P < 0.0001). PEEP alone did not reduce the amount of atelectasis or improve oxygenation. A recruitment maneuver + zero end-expiratory pressure had a transient positive effect on respiratory function. All values are presented as mean +/- SD. CONCLUSIONS: A recruitment maneuver followed by PEEP reduced atelectasis and improved oxygenation in morbidly obese patients, whereas PEEP or a recruitment maneuver alone did not.

Visualisation and quantification of peri-operative myocardial infarction after coronary artery bypass surgery with contrast-enhanced magnetic resonance imaging.

AIMS: To evaluate if elevated biochemical marker levels after coronary artery bypass grafting (CABG) correspond to the amount of peri-operatively infarcted myocardium, quantified by magnetic resonance imaging (MRI) post-operatively. METHODS AND RESULTS: A total of 23 patients without evidence of previous myocardial infarction or myocarditis and with normal pre-operative ECG and left ventricular function and who underwent elective, primary CABG, without any other concomitant cardiac surgery, were included. Plasma creatinine kinase MB (CK-MB) and troponin I and T were measured on the first, second and fourth post-operative days. Between the fourth and ninth post-operative days, cardiac MRI was carried out. Infarctions were found in 18 patients. The infarction mass at MRI was numerically largest in patients with transmural infarctions, all of whom had a CK-MB more than five times the upper normal limit. All three cardiac markers correlated to the mass of infarction. CONCLUSION: Elevated biochemical markers after CABG correspond to the amount of peri-operatively infarcted myocardium.