Simon Schalla

Diagnostic Performance of Noninvasive Myocardial Perfusion Imaging Using Single-Photon Emission Computed Tomography, Cardiac Magnetic Resonance, and Positron Emission Tomography Imaging for the Detection of Obstructive Coronary Artery Disease: A Meta-Analysis

OBJECTIVES This study aimed to determine the diagnostic accuracy of the 3 most commonly used noninvasive myocardial perfusion imaging modalities, single-photon emission computed tomography (SPECT), cardiac magnetic resonance (CMR), and positron emission tomography (PET) perfusion imaging for the diagnosis of obstructive coronary artery disease (CAD). Additionally, the effect of test and study characteristics was explored. BACKGROUND Accurate detection of obstructive CAD is important for effective therapy. Noninvasive myocardial perfusion imaging is increasingly being applied to gauge the severity of CAD. METHODS Studies published between 1990 and 2010 identified by PubMed search and citation tracking were examined. A study was included if a perfusion imaging modality was used as a diagnostic test for the detection of obstructive CAD and coronary angiography as the reference standard (≥50% diameter stenosis). RESULTS Of the 3,635 citations, 166 articles (n = 17,901) met the inclusion criteria: 114 SPECT, 37 CMR, and 15 PET articles. There were not enough publications on other perfusion techniques such as perfusion echocardiography and computed tomography to include these modalities into the study. The patient-based analysis per imaging modality demonstrated a pooled sensitivity of 88% (95% confidence interval [CI]: 88% to 89%), 89% (95% CI: 88% to 91%), and 84% (95% CI: 81% to 87%) for SPECT, CMR, and PET, respectively; with a pooled specificity of 61% (95% CI: 59% to 62%), 76% (95% CI: 73% to 78%), and 81% (95% CI: 74% to 87%). This resulted in a pooled diagnostic odds ratio (DOR) of 15.31 (95% CI: 12.66 to 18.52; I(2) 63.6%), 26.42 (95% CI: 17.69 to 39.47; I(2) 58.3%), and 36.47 (95% CI: 21.48 to 61.92; I(2) 0%). Most of the evaluated test and study characteristics did not affect the ranking of diagnostic performances. CONCLUSIONS SPECT, CMR, and PET all yielded a high sensitivity, while a broad range of specificity was observed. SPECT is widely available and most extensively validated; PET achieved the highest diagnostic performance; CMR may provide an alternative without ionizing radiation and a similar diagnostic accuracy as PET. We suggest that referring physicians consider these findings in the context of local expertise and infrastructure.

Cardiac involvement in Churg‐Strauss syndrome

OBJECTIVE Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis. Previous studies showing cardiac involvement in CSS patients were limited in the number of patients and were often based solely on clinical manifestations. The aim of the present study was to determine in detail the incidence of cardiac involvement in a large population of ambulatory CSS patients. METHODS Thirty-two consecutive patients with CSS in remission (mean +/- SD duration of disease between diagnosis and enrollment 6.1 +/- 5.8 years, mean +/- SD age 61 +/- 10 years) who were previously unaware of cardiac involvement were compared with 32 randomly selected age- and sex-matched control subjects, using clinical evaluation, electrocardiography (EKG), echocardiography, and cardiac magnetic resonance imaging (MRI). RESULTS Detailed cardiac evaluation revealed a 62% prevalence of cardiac involvement in CSS patients compared with 3% in controls (P < 0.001), with clinical symptoms in 26% and 3%, respectively (P = 0.009), EKG abnormalities in 66% and 3%, respectively (P < 0.001), and echocardiographic defects in 50% and 3%, respectively (P < 0.001). Cardiac MRI detected cardiac manifestations in 62% of CSS patients. In the presence of cardiac MRI abnormalities, echocardiography could detect cardiac involvement with a sensitivity of 83% and a specificity of 80%. The absence of symptoms or EKG abnormalities did not exclude cardiac involvement, because abnormalities could still be detected in 38% of these patients at the time of echocardiography or cardiac MRI. CONCLUSION These results demonstrate a high incidence of cardiac involvement in CSS patients. Systematic cardiac evaluation including detailed imaging is required to properly identify CSS patients with cardiac involvement.

Cardiac Magnetic Resonance Imaging Findings and the Risk of Cardiovascular Events in Patients With Recent Myocardial Infarction or Suspected or Known Coronary Artery Disease

The goal of this study was to review the prognostic value of cardiac magnetic resonance (CMR) imaging findings for future cardiovascular events in patients with a recent myocardial infarction (MI) and patients with suspected or known coronary artery disease (CAD). Although the diagnostic value of CMR findings is established, the independent prognostic association with future cardiovascular events remains largely unclear. Studies published by February 2013, identified by systematic MEDLINE and EMBASE searches, were reviewed for associations between CMR findings (left ventricular ejection fraction [LVEF], wall motion abnormalities [WMA], abnormal myocardial perfusion, microvascular obstruction, late gadolinium enhancement, edema, and intramyocardial hemorrhage) and hard events (all-cause mortality, cardiac death, cardiac transplantation, and MI) or major adverse cardiovascular events (MACE) (hard events and other cardiovascular events defined by the authors of the evaluated papers). Fifty-six studies (n = 25,497) were evaluated. For patients with recent MI, too few patients were evaluated to establish associations between CMR findings and hard events. LVEF (range of adjusted hazard ratios [HRs]: 1.03 to 1.05 per % decrease) was independently associated with MACE. In patients with suspected or known CAD, WMA (adjusted HRs: 1.87 to 2.99), inducible perfusion defects (adjusted HRs: 3.02 to 7.77), LVEF (adjusted HRs: 0.72 to 0.82 per 10% increase), and infarction (adjusted HRs: 2.82 to 9.43) were independently associated with hard events, and the presence of inducible perfusion defects was associated with MACE (adjusted HRs: 1.76 to 3.21). The independent predictor of future cardiovascular events for patients with a recent MI was LVEF, and the predictors for patients with suspected or known CAD were WMA, inducible perfusion defects, LVEF, and presence of infarction.

Replacement and reactive myocardial fibrosis in idiopathic dilated cardiomyopathy: comparison of magnetic resonance imaging with right ventricular biopsy

Background The presence of focal myocardial fibrosis, also called scar or replacement fibrosis, detected with late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) is a predictor of adverse outcome in patients with idiopathic dilated cardiomyopathy (DCM). 1,2 Increased interstitial (reactive) fibrosis determined with histological staining from endomyocardial biopsy (EMB) specimens has been described in DCM and associated with an adverse prognosis and impaired response to therapeutic interventions in selected groups of patients with DCM. 3―6 Aims We sought to describe the patterns of focal fibrosis in a group of patients with DCM and correlate focal fibrosis with interstitial fibrosis, myocardial viral load, and inflammation. A pilot study in 10 autopsies was performed to compare interstitial fibrosis from right ventricular (RV) with left ventricular (LV) EMB. Methods Study subjects were 60 consecutive patients with DCM (globally impaired systolic LV function not due to myocardial infarction, significant coronary artery disease, hypertension, valvular disease, or other known causes) referred to our hospital for EMB and CMR. Patients (n = 1) with infarct-like subendocardial or transmural LGE within the territory of a coronary artery and corresponding regional wall motion abnormalities only were not included to avoid the inclusion of patients with an embolic event. Three patients did not agree to participate resulting in a study population of 56. The study was approved.

Intravenous immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial biopsy-proven high PVB19 viral load.

BACKGROUND Parvovirus B19 (PVB19) persistence in the heart has been associated with progressive cardiac dysfunction and evolution to dilated cardiomyopathy. In the present study, we investigated whether immunomodulation with intravenous immunoglobulin (IVIg) in addition to conventional heart failure therapy is safe and achieves virus reduction. Such therapy might improve cardiac function in patients with chronic dilated cardiomyopathy (DCM) and a significant PVB19 viral load in the heart. METHODS PVB19 viral load was studied in 25 post-mortem cardiac samples of patients with a normal heart. Then, 17 consecutive patients (mean age 53 +/-3 years) with DCM and symptomatic heart failure for >1 year with a PVB19 viral load in endomyocardial biopsies of >250 copies/microg DNA were treated with a high dose of IVIg (2 g/kg). RESULTS The post-mortem cardiac samples revealed a PVB19 presence in 80% with a mean load of 131 +/-40 copies/microg DNA. In the treated patients, IVIg resulted in a significant decrease of PVB19 viral load from 1,420 +/-216 to 619 +/-200 copies/microg DNA (P=0.004) and significantly improved the ejection fraction from 33 +/-3% 6 months before treatment and 34 +/-3% at baseline to 41 +/-3% 6 months (P=0.001) after IVIg therapy. The New York Heart Association classification significantly improved from 2.5 +/-0.1 at baseline to 2.1 +/-0.1 at follow-up (P=0.004). No therapy-related complications were noted. CONCLUSIONS The present pilot study demonstrates that IVIg significantly reduces viral load and improves cardiac function in patients with DCM related to increased PVB19 viral load in the heart.

Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

BackgroundMyotonic dystrophy type 1 (MD1) is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1.MethodsEighty MD1 patients underwent physical examination, electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR). Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length.ResultsFunctional and structural abnormalities were detected in 35 patients (44%). Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%). In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04), male gender (p < 0.001) and abnormal ECG (p < 0.001). Disease duration, CTG repeat length, severity of neuromuscular symptoms and NT-proBNP level did not predict the presence of myocardial abnormalities.ConclusionsCMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis

BACKGROUND To investigate the prevalence and prognostic relevance of cardiac involvement in an ANCA-associated vasculitis (AAV) population of eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA) patients. METHODS Prospective cohort study of fifty EGPA and forty-one GPA patients in sustained remission without previous in-depth cardiac screening attending our clinical immunology outpatient department. Cardiac screening included clinical evaluation, ECG, 24-hour Holter registration, echocardiography and cardiac magnetic resonance imaging (CMR) with coronary angiography and endomyocardial biopsy upon indication. Fifty age-, sex- and cardiovascular risk factor-matched control subjects were randomly selected from a population study. Long-term outcome was assessed using all-cause and cardiovascular mortality. RESULTS A total of 91 AAV-patients (age 60±11, range 63-87years) were compared to 50-matched control subjects (age 60±9years, range 46-78years). ECG and echocardiography demonstrated cardiac abnormalities in 62% EGPA and 46% GPA patients vs 20% controls (P<0.001 and P=0.014, respectively). A total of 69 AAV-patients underwent additional CMR, slightly increasing the prevalence of cardiac involvement to 66% in EGPA and 61% in GPA patients. After a mean follow-up of 53±18months, presence of cardiac involvement using ECG and echocardiography in AAV-patients showed increased all-cause and cardiovascular mortality (Log-rank P=0.015 and Log-rank P=0.021, respectively). CONCLUSION Cardiac involvement in EGPA and GPA patients with sustained remission is high, even if symptoms are absent and ECG is normal. Moreover, cardiac involvement is a strong predictor of (cardiovascular) mortality. Therefore, risk stratification using cardiac imaging is recommended in all AAV-patients, irrespective of symptoms or ECG abnormalities.

Improvement of image quality of non‐invasive coronary artery imaging with magnetic resonance by the use of the intravascular contrast agent Clariscan™ (NC100150 injection) in patients with coronary artery disease

To assess the feasibility of Clariscan™, an intravascular contrast agent, for free breathing, navigator assisted, high resolution, three‐dimensional‐magnetic resonance coronary angiography (MRCA) in patients, as extracellular contrast agents are unfavorable for the improvement of image quality.

Visualization of Coronary Wall Atherosclerosis in Asymptomatic Subjects and Patients with Coronary Artery Disease Using Magnetic Resonance Imaging

Background Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD. Methodology Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4±10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1±4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared. Principal Findings Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05). Conclusions In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis. Trial registration ClinicalTrials.gov NCT00456950

Myocardial Perfusion Imaging Using OMNISCAN: A Dose Finding Study for Visual Assessment of Stress‐Induced Regional Perfusion Abnormalities

BACKGROUND Different doses of contrast agent are applied for magnetic resonance perfusion studies and mainly semiquantitative approaches have been reported for analysis. We aimed to determine the optimal dose for a visual detection of perfusion defects. METHODS 49 patients (59+/-8 years; 33 male) scheduled for invasive angiography were examined at stress (0.14 mg adenosine/kg body weight/minute) and rest using a TFE-EPI hybrid sequence (Philips ACS NT; 1.5 T). Patients were assigned to three different dose groups of gadodiamide (0.05, 0.1, and 0.15 mmol/kg body weight) injected as a bolus via a peripheral vein. Visual assessment was used to detect a regional reduction of peak signal intensity or speed of contrast agent inflow at stress in comparison to rest. RESULTS Prevalence for coronary artery disease was 67%. The highest diagnostic accuracy was reached for a dose of 0.1 mmol gadodiamide/kg body weight (86% p=nonsignificant vs. 0.15 and 0.05 mmol gadodiamide/kg). At this dose, no major artifacts related to the contrast agent were found. CONCLUSIONS Visual assessment of myocardial perfusion using a high-flow rate contrast agent bolus injection and a TFE-EPI sequence can be best achieved with a dose of gadodiamide 0.1 mmol/kg bodyweight.