Coronary calcium score in COVID-19 survivors: Association with cardiac injury and cardiac function after 6 weeks.

Aims: Cardiac manifestations are common in COVID-19, often elevated serum troponin levels or myocardial dysfunction on trans-thoracic echocardiography (TTE) is observed. Both parameters are associated with increased in-hospital mortality. Possibly, subclinical coronary atherosclerosis plays a role, of which severity can be assessed by calculating the coronary artery calcium (CAC) score. This study aims to determine the relation between coronary atherosclerosis and cardiac manifestations in COVID-19 survivors. Methods: This study was conducted at the Leiden University Medical Center. All patients admitted for COVID-19 were included and scheduled for a 6-week follow-up visit with trans-thoracic echocardiography (TTE). CAC was assessed according to an ordinal score on non-gated, non-contrast enhanced computed tomography of the chest. Patients with and without CAC were compared on cardiac injury as reflected by elevated serum troponin levels and impaired cardiac function assessed through TTE. Results: In total, 146 patients were included. Mean age was 62 years and 62 % of the patients were male. During admission, patients with CAC showed significantly higher levels of troponin (19 ng/L vs 10 ng/L; p < 0.01). Overall, mild echocardiographic abnormalities were seen; 12 % showed reduced left ventricular function (left ventricular ejection fraction of <50 %) and 14 % reduced right ventricular function (tricuspid annular planar systolic excursion ≤17 mm). Following multivariable adjustments, there was no significant relation between CAC and myocardial function at 6 weeks. Conclusion: The present study shows that coronary atherosclerosis is associated with cardiac injury in COVID-19 survivors. However, no significant relation with impaired cardiac function was demonstrated.

Prognostic value of the coronary artery calcium score in suspected coronary artery disease: a study of 644 symptomatic patients.

AIM: The long-term value of coronary artery calcium (CAC) scanning has not been studied extensively in symptomatic patients, but was evaluated by us in 644 consecutive patients referred for stable chest pain. METHODS: We excluded patients with a history of cardiovascular disease and with a CAC score of zero. CAC scanning was done with a 16-row MDCT scanner. Endpoints were: (a) overall mortality, (b) mortality or non-fatal myocardial infarction and (c) the composite of mortality, myocardial infarction or coronary revascularisation. Revascularisations within 1 year following CAC scanning were not considered. RESULTS: The mean age of the 320 women and 324 men was 63 years. Follow-up was over 8 years. There were 58 mortalities, while 22 patients suffered non-fatal myocardial infarction and 24 underwent coronary revascularisation, providing 104 combined endpoints. Cumulative 8­year survival was 95% with CAC score <100, 90% in patients with CAC score >100 and <400, and 82% with CAC score ≥400 Agatston units. Risk of mortality with a CAC score >100 and ≥400 units was 2.6 [95% confidence interval (CI) 1.23-5.54], and 4.6 (95% CI 2.1-9.47) respectively. After correction for clinical risk factors, CAC score remained independently associated with increased risk of cardiac events. CONCLUSIONS: Risk increased with increasing CAC score. Patients with CAC >100 or ≥400 Agatston units were at increased risk of major adverse cardiac events and are eligible for preventive measures. CAC scanning provided incremental prognostic information to guide the choice of diagnostic and therapeutic options in many subjects evaluated for chest pain.

Effects of caffeine intake prior to stress cardiac magnetic resonance perfusion imaging on regadenoson- versus adenosine-induced hyperemia as measured by T1 mapping.

The antagonistic effects of caffeine on adenosine receptors are a possible cause of false-negative stress perfusion imaging. The purpose of this study was to determine the effects of coffee intake <4 h prior to stress perfusion cardiac magnetic resonance imaging (CMR) in regadenoson- versus adenosine-induced hyperemia as measured with T1-mapping. 98 consecutive patients with suspected coronary artery disease referred for either adenosine or regadenoson perfusion CMR were included in this analysis. Twenty-four patients reported coffee consumption <4 h before CMR (15 patients with adenosine, and 9 patients with regadenoson); 74 patients reported no coffee intake (50 patients with adenosine, and 24 patients with regadenoson). T1 mapping was performed using a modified look-locker inversion recovery sequence. T1 reactivity was determined by subtracting T1rest from T1stress. T1rest, T1stress, and T1 reactivity in patients referred for regadenoson perfusion CMR were not significantly different when comparing patients with <4 h coffee intake and patients who reported no coffee intake (976 ± 4 ms, 1019 ± 48 ms, and 4.4 ± 3.2% vs 971 ± 33 ms, 1023 ± 43 ms, and 5.4 ± 2.4%) (p = 0.70, 0.79, and 0.40), and similar to values in patients without coffee intake undergoing adenosine CMR. In patients with <4 h coffee intake, T1stress, and T1 reactivity were significantly lower for adenosine (898 ± 51 ms, and -7.8 ± 5.0%) compared to regadenoson perfusion CMR (p < 0.001). Coffee intake <4 h prior to regadenoson perfusion CMR has no effect on stress-induced hyperemia as measured with T1 mapping.

Diagnostic and prognostic value of absence of coronary artery calcification in patients with stable chest symptoms.

UNLABELLED: The aim of this study was to determine the prognostic value of a coronary artery calcium score (CACS) of 0 in patients with stable chest symptoms and to compare it as a first-line test with bicycle exercise testing (X-ECG). Altogether, 315 consecutive patients over 44 years of age, with stable chest symptoms and no previous diagnosis of coronary artery disease (CAD) visited the outpatient clinic of our community hospital and underwent both CACS and X-ECG. The mean age was 60.54 years (SD 9.7; range 45-88 years). Of these patients, 141 had no detectable coronary calcium (44.8%) We excluded patients who did not sign informed consent (n = 4). Three patients were lost to follow-up. The follow-up group therefore consisted of 134 patients. The mean follow-up period was 44.6 months (25th-75th percentile: 35.5-54.3 months), during which no major adverse cardiac events (MACE) occurred. The negative predictive value (NPV) was 100%. X-ECG was negative in only 89 patients, equivocal in 39 patients and false-positive in 6 patients requiring additional stress myocardial imaging in 45 patients. NPV as a first-line test was therefore 66.4%. IN CONCLUSION: patients over 44 years with stable chest symptoms and no detectable coronary calcium have an excellent prognosis. CACS performs better compared with X-ECG as an initial test in patients with stable chest symptoms.

[Coronary calcium score using CT in the diagnosis of 2 patients with acute chest pain]. / Coronaire calciumscore met behulp van CT bij de diagnostiek van 2 patiënten met acute thoracale pijn.

A 38-year-old man presented with severe retrosternal pain that had persisted for several days. Physical examination, resting ECG and circulating levels of cardiac markers were normal. The patient had continuous pain during a bicycle test, but no signs of myocardial ischaemia were found. A CT scan was performed, and the resulting CT calcium score was 40 Agatston units (AU; > 90th percentile). Coronary angiography showed severe coronary artery disease. An arterial bypass operation took place. Recovery was uncomplicated and the patient remained free of symptoms. A 55-year-old man experienced midsternal pain that lasted 20 minutes before spontaneously subsiding. The ECG and troponine levels were normal. One week later, there were no abnormalities during a bicycle test and the CT calcium score was 0 AU. Therefore, there was no indication of coronary artery disease and a watchful waiting approach was taken. After 1 year of follow-up, the patient remained free of symptoms. For patients aged 45 years or more with acute chest pain and a CT calcium score of 0 AU, further cardiac evaluation is unnecessary. For patients aged less than 45 years, a CT calcium score greater than o is abnormal and requires additional cardiac evaluation.

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability.

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 µg/kg/min or more with a maximum of 40 µg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 µg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised. DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal.

[Dobutamine stress magnetic resonance imaging (DS-MRI), a valuable tool for the diagnosis of ischemic heart disease]. / Dobutaminestress-MRI van het hart: een waardevolle onderzoekstechniek voor de diagnostiek van ischemische hartziekten.

OBJECTIVE: Assessment of the clinical applicability of DS-MRI for the detection of myocardial ischemia and myocardial viability. DESIGN: Prospective. METHOD: In the period from 1 November 1999 to 31 October 2000, patients with suspected coronary artery disease who could not be studied by means of conventional bicycle ergometry underwent breath-hold DS-MRI (1 Tesla) 4 days after cessation of anti-ischemic medication. Three left ventricular short-axis planes were examined for the occurrence of disorders in wall movement during infusion of increasing doses of dobutamine (10, 20, 30 and 40 micrograms/kg/min). Temporary recovery of wall thickening in a previously diminished or non-contracting segment under 5 micrograms/kg/min of dobutamine was considered proof of viability. Development of hypo-, a- or dyskinesia at higher doses of dobutamine was taken to indicate ischemia. If the DS-MRI test was positive for ischemia, coronary angiography was performed. If indicated, this was followed by revascularisation. If DS-MRI did not reveal ischemia, the patient was seen at the outpatient department. RESULTS: Of the 100 patients (62 men and 38 women with an average age of 62 years, SD = 12) subjected to DS-MRI, 95 yielded results that were suitable for diagnosis. Of the 42 patients with DS-MRI scans that were considered positive for ischemia and in whom coronary angiography was subsequently performed, 41 had such coronary abnormalities that revascularisation was indicated. One patient was false-positive. All 53 patients with non-ischemic DS-MRI scans were followed-up for 11-23 months (mean 17 months). One patient died suddenly 2 weeks after the MRI-test. The other 52 patients did not experience any coronary events nor sudden cardiac death. The predictive value of a positive DS-MRI scan for ischemia was 98% and the predictive value of a negative DS-MRI scan was also 98%. CONCLUSION: DS-MRI is a safe diagnostic method for the detection or exclusion of myocardial ischemia and viability in patients with suspected coronary artery disease.

Pravastatin and endothelium dependent vasomotion after coronary angioplasty: the PREFACE trial.

OBJECTIVE: To test the hypothesis that the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor pravastatin ameliorates endothelium mediated responses of dilated coronary segments: the PREFACE (pravastatin related effects following angioplasty on coronary endothelium) trial. DESIGN: A double blind, randomised, placebo controlled, multicentre study. SETTING: Four hospitals in the Netherlands. PATIENTS: 63 non-smoking, non-hypercholesterolaemic patients scheduled for elective balloon angioplasty (pravastatin 34, placebo 29). INTERVENTIONS: The effects of three months of pravastatin treatment (40 mg daily) on endothelium dependent vasomotor function were studied. Balloon angioplasty was undertaken one month after randomisation, and coronary vasomotor function tests using acetylcholine were performed two months after balloon angioplasty. The angiograms were analysed quantitatively. MAIN OUTCOME MEASURES: The efficacy measure was the acetylcholine induced change in mean arterial diameter, determined in the dilated segment and in an angiographically normal segment of an adjacent non-manipulated coronary artery. RESULTS: Increasing acetylcholine doses produced vasoconstriction in the dilated segments (p = 0.004) but not in the normal segments. Pravastatin did not affect the vascular response to acetylcholine in either the dilated segments (p = 0.09) or the non-dilated sites. Endothelium dependent vasomotion in normal segments was correlated with that in dilated segments (r = 0.47, p < 0.001). There were fewer procedure related events in the pravastatin group than in the placebo group (p < 0.05). CONCLUSIONS: Endothelium dependent vasomotion in normal segments is correlated with that in dilated segments. A significant beneficial effect of pravastatin on endothelial function could not be shown, but in the dilated segments there was a trend towards a beneficial treatment effect in the pravastatin group.

Reproducibility of left ventricular size, shape and mass with echocardiography, magnetic resonance imaging and radionuclide angiography in patients with anterior wall infarction. A plea for core laboratories.

After myocardial infarction, left ventricular volume and ejection fraction can be assessed by echocardiography, magnetic resonance imaging and radionuclide angiography to guide therapy and determine prognosis. Whether a measured parameter gives the same results irrespective of the method used and the observer who performs the analysis is only partly known. Intra-observer and inter-observer variability were determined for echo and magnetic resonance imaging. Left ventricular ejection fraction measured by these techniques was related to radionuclide angiograms performed in the same period. Intra-observer variability for both echo and MRI was low and in most instances below 5%. Inter-observer variability for the echo and MRI measurements were substantially higher than intra-observer variability. Comparison of the three imaging modalities revealed systematic differences. Therefore, in clinical studies, left ventricular volume and function parameters have to be measured with the same technique and by the same observer in qualified core laboratories.

Imaging of recurrent ventricular septal defect and supravalvular pulmonary stenosis eight years after assumed total surgical repair of tetralogy of Fallot.

A 42-year-old man underwent assumed total surgical repair of an acyanotic tetralogy of Fallot: a perimembranous ventricular septal defect (VSD) was closed with a dacron patch and myectomy of the infundibulum of the right ventricular outflow tract was performed. Reexamination eight years later revealed a large recurrent VSD and by surprise a narrow supravalvular ridge above rudimentary pulmonary cusps in the pulmonary trunk, leading to a pressure drop of 70 mmHg across the supravalvular stenosis. The latter finding was not recognized during the operation eight years before. The diagnosis could noninvasively be established by means of magnetic resonance imaging. During revision surgery the VSD was closed and an aortic homograft was inserted as conduit between the right ventricle and the pulmonary artery.

Assessment of left ventricular volume and mass by cine magnetic resonance imaging in patients with anterior myocardial infarction intra-observer and inter-observer variability on contour detection.

Remodeling of the left ventricle after myocardial infarction can be documented by calculation of left ventricular volume and mass, using endocardial and epicardial tracings of multilevel multiphase short-axis cine magnetic resonance (MR) imaging series. We assessed left ventricular volume and mass from 8 slices and during 12 phases of the cardiac cycle in seven patients with an anterior wall myocardial infarction; one patient was studied twice, leaving eight MR examinations to be evaluated. Purpose of this study was to assess the intra-observer and inter-observer variability of epicardial volume, endocardial volume, and left ventricular mass from contours manually traced by two independent observers. For the eight MR examinations, epicardial volume was found to be 292 +/- 51 ml (mean +/- SD) at end-diastole, which decreased to 237 +/- 55 ml at end-systole. Endocardial volume was 141 +/- 31 ml at end-diastole, which decreased to 79 +/- 27 ml at end-systole. Left ventricular ejection fraction was 45 +/- 8%. Mean left ventricular mass, when averaged over all patient studies and all phases, was 159 +/- 30 g. Intra-observer and inter-observer variability were found to be 3.5% and 5.2% for endocardial volume, 2.0% and 2.5% for epicardial volume, and 3.6% and 3.6% for left ventricular mass, respectively. The contour analysis showed a statistically significant phase effect in the endocardial contour in the midventricular slices, which was resolved after establishing a more precise definition for the tracing of the endocardial border. In conclusion, left ventricular volume and mass in patients with an anterior wall myocardial infarction can be assessed with high reproducibility and reliability from manual contour tracings. A precise protocol for the definition of endocardial and epicardial contours is required to obtain reproducible and reliable results.

Quantitative analysis of regional left ventricular function after myocardial infarction in the pig assessed with cine magnetic resonance imaging.

To assess the accuracy of quantitative analysis of global and regional wall motion and wall thickening of the left ventricle with cine magnetic resonance (MR), images obtained in eight pigs before and after myocardial infarction were compared with those obtained using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced multislice spin-echo MR imaging and determination of pathology. The region with abnormal wall motion and wall thickening, as determined with cine MR imaging, identified the same region of infarction as indicated by Gd-DTPA-enhanced spin-echo MR imaging and pathology. Within the infarcted region wall motion and wall thickening analyzed with the centerline method were significantly reduced. We conclude that the use of quantitative analysis of cine MR images accurately determines localization and extent of regional left ventricular dysfunction in the infarcted heart in vivo. This analysis using dedicated software including the centerline method allows sequential assessment of regional left ventricular function in normal and infarcted hearts.

Magnetic resonance imaging during dobutamine stress for detection and localization of coronary artery disease. Quantitative wall motion analysis using a modification of the centerline method.

BACKGROUND: Quantitative measurement of wall motion is essential to assess objectively the functional significance of coronary artery disease. We developed a quantitative wall thickening analysis on stress magnetic resonance images. This study was designed to assess the clinical value of magnetic resonance imaging (MRI) during dobutamine stress for detection and localization of myocardial ischemia in patients with suspected coronary artery disease. METHODS AND RESULTS: Thirty-nine consecutive patients with clinically suspected coronary artery disease referred for coronary arteriography and 10 normal volunteers underwent gradient-echo MRI at rest and during peak dobutamine stress (infusion rate, 20 micrograms.kg-1.min-1). MRI was performed in the short-axis plane at four adjacent levels. Display in a cine loop provided a qualitative impression of regional wall motion (cine MRI). A modification of the centerline method was applied for quantitative wall motion analysis by means of calculation of percent systolic wall thickening. Short-axis cine MRI images were analyzed at 100 equally spaced chords constructed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours. Dobutamine MRI was considered positive for coronary artery disease if the percent systolic wall thickening of more than four adjacent chords was < 2 SD below the mean values obtained from the normal volunteers. The overall sensitivity of dobutamine MRI for the detection of significant coronary artery disease (diameter stenosis > or = 50%) was 91% (30 of 33), specificity was 80% (5 of 6), and accuracy was 90% (35 of 39). The sensitivity for identifying one-vessel disease was 88% (15 of 17), for two-vessel disease 91% (10 of 11), and for three-vessel disease 100% (5 of 5). The sensitivity for detection of individual coronary artery lesions was 75% for the left anterior descending coronary artery, 87% for the right coronary artery, and 63% for the left circumflex coronary artery. CONCLUSIONS: Dobutamine MRI clearly identifies wall motion abnormalities by quantitative analysis using a modification of the centerline method. Dobutamine MRI is an accurate method for detection and localization of myocardial ischemia and may emerge as a new noninvasive approach for evaluation of patients with known or suspected coronary artery disease.

Comparison of magnetic resonance imaging studies with enzymatic indexes of myocardial necrosis for quantification of myocardial infarct size.

To evaluate the potential of gadolinium-diethylene triamine pentaacetic acid (DTPA)-enhanced magnetic resonance imaging (MRI) in the quantification of infarct size in patients with a first acute myocardial infarction, 24 patients with a first acute myocardial infarction were studied by electrocardiographic gated MRI at a mean of 4.3 days after the acute event. Multislice, single-phase, T1-weighted, spin-echo MRI in the true short-axis plane was performed 20 minutes after intravenous injection of gadolinium-DTPA (0.15 mmol/kg of body weight). Circumscript myocardial regions of increased signal intensity on gadolinium-DTPA-enhanced images were considered to be infarcted. Infarct size (in g) was determined using Simpson's rule, and was compared with that based on cumulative release of alpha-hydroxybutyrate dehydrogenase activity in plasma and with peak creatine kinase-MB level in plasma. Infarct size quantified with MRI correlated well with "enzymatic" infarct size (in g equivalents) (y = 0.99 x + 0.71; r = 0.93; p = 0.0001) and peak creatine kinase-MB levels (r = 0.72; p = 0.002). It is concluded that gadolinium-DTPA-enhanced MRI enables accurate quantification of infarct size in patients with a first acute myocardial infarction.

Sequential analysis of infarcted and normal myocardium in piglets using in vivo gadolinium-enhanced MR images.

Gadolinium-enhanced magnetic resonance (MR) imaging was performed before, and 1 and 3 wk after coronary occlusion in domestic piglets. After administration of the contrast agent gadopentetate dimeglumine, two different enhancement patterns within the infarcted region were observed. The first pattern, showing peripheral enhancement of the infarcted region with absence of contrast in the center, was seen at 1 wk after occlusion at 5 min after administration of the contrast agent. The second pattern showed signal enhancement of the center of the infarcted region and was observed at 1 wk after occlusion, 30 min following contrast administration, and at 3 wk after occlusion, both 5 and 30 min following contrast administration. Infarct size and left ventricular (LV) mass by MR imaging, measured 3 wk after infarction, corresponded well with pathologic assessment. LV mass, measured by static and dynamic MR imaging, increased during the period of investigation. It is concluded that gadolinium-enhanced MR imaging clearly identifies infarcted myocardium early and late after coronary occlusion in the piglet. Combined results of infarct size and LV mass can be obtained simultaneously during one imaging procedure.

Usefulness of ultrafast magnetic resonance imaging in healed myocardial infarction.

The value of ultrafast magnetic resonance imaging (MRI) in the assessment of dynamic contrast enhancement and myocardial perfusion abnormalities was evaluated in 20 patients with healed myocardial infarction, who also underwent 2-dimensional echocardiography. At baseline and after bolus injection of the paramagnetic contrast agent gadolinium-diethylenetriaminepentaacetic acid (DTPA) (0.04 mmol/kg body weight), single-level short-axis MRI was performed every third RR interval with an acquisition time of 500 ms. Myocardial signal intensities were measured in transmural myocardial regions of interest. After gadolinium-DTPA injection, infarcted and normal myocardium demonstrated a signal intensity enhancement of 50 and 134%, respectively (p < 0.001). A signal intensity of normal relative to infarcted myocardium increased from 1.25 +/- 0.22 (SD) before to 1.91 +/- 0.41 after gadolinium-DTPA (p < 0.001). The rate of signal increase in the infarcted and normal myocardium was 5.17 +/- 2.22 and 18.99 +/- 9.96 s-1 (p < 0.001), respectively. Ultrafast MRI using gadolinium-DTPA bolus administration clearly identifies myocardial perfusion abnormalities in patients with healed myocardial infarction. The infarct site on MRI corresponded with the location of wall motion asynergy determined by echocardiography. It is concluded that gadolinium-DTPA-enhanced ultrafast MRI provides noninvasive assessment of myocardial perfusion in patients with proven coronary artery disease.

Assessment of acute myocardial infarction by nuclear imaging techniques.

In recent years, nuclear cardiology techniques have been successfully applied in patients with acute myocardial infarction. These scintigraphic measurements have provided important diagnostic, therapeutic, and prognostic information based on the extent of myocardial damage and the functional reserve of the left ventricle. In particular, in the thrombolytic era, myocardial perfusion imaging and radionuclide angiography have been shown to be valuable methods for studying the effects of reperfusion on the extent of myocardial damage. Nuclear magnetic resonance imaging, preferably with contrast enhancement, is one of the newly developed nuclear imaging techniques that have probably the greatest potential in accurately delineating myocardial infarct size and in evaluating left ventricular function. Radionuclide procedures, on the other hand, employ more biologically oriented tracers and are therefore capable of monitoring biochemical changes in the course of acute myocardial infarction.