Publications by authors named "Albert C van Rossum"

279 Publications

Managing older patients with heart failure calls for a holistic approach.

ESC Heart Fail 2021 Apr 8. Epub 2021 Apr 8.

Department of Internal Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, Amsterdam, 1081HV, The Netherlands.

Aims: This study aims to assess the presence of geriatric domain impairments in an older heart failure (HF) outpatient population and to relate these domain impairments with 1 year mortality risk in comparison with a geriatric outpatient population without HF.

Methods And Results: Data were used from two different prospective cohort studies: 241 outpatients with HF (mean age 78 ± 9 years, 48% female) and 686 geriatric outpatients (mean age 80 ± 7 years, 55% female). We similarly assessed the following geriatric domains in both cohorts: physical function, nutritional status, polypharmacy, cognitive function, and activities in daily living. Cox proportional hazards analyses were used to relate individual domains to 1 year mortality risk in both populations and to compare 1 year mortality risk between both populations. Of the patients with HF, 34% had impairments in ≥3 domains, compared with 38% in geriatric patients. One-year mortality rates were 13% and 8%, respectively, in the HF and geriatric populations; age-adjusted and sex-adjusted hazard ratio (95% confidence interval) for patients with HF compared with geriatric patients was 1.7 (1.3-2.6). The individual geriatric domains were similarly associated with 1 year mortality risk in both populations. Compared with zero to two impaired domains, age-adjusted and sex-adjusted mortality risk (hazard ratio, 95% confidence interval) for three, four, or five impaired domains ranged from 1.6 (0.6-4.2) to 6.5 (2.1-20.1) in the HF population and from 1.4 (0.7-2.9) to 7.9 (2.9-21.3) in the geriatric population.

Conclusions: In parallel with geriatric patients, patients with HF often have multiple geriatric domain impairments that adversely affect their prognosis. This similarity together with the findings that patients with HF have a higher 1 year mortality risk than a general geriatric population supports the integration of a multi-domain geriatric assessment in outpatient HF care.
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http://dx.doi.org/10.1002/ehf2.13292DOI Listing
April 2021

Reversible Cause of Cardiac Arrest and Secondary Prevention Implantable Cardioverter Defibrillators in Patients With Coronary Artery Disease: Value of Complete Revascularization and LGE-CMR.

J Am Heart Assoc 2021 Apr 6:e019101. Epub 2021 Apr 6.

Department of Cardiology Amsterdam UMC, Vrije Universiteit AmsterdamAmsterdam Cardiovascular Sciences Amsterdam Netherlands.

Background In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar-related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter-defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD-per-guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD-off-label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5-4.6) of follow-up, ADT developed in 15% of the ICD-off-label group versus 43% of the ICD-per-guideline group. Time to ADT was comparable in the ICD-off-label and ICD-per-guideline groups (hazard ratio (HR), 0.46; =0.08). No difference in mortality was observed (HR, 0.95; =0.93). Independent predictors of ADT included age (HR, 1.03; =0.01), left ventricular end-diastolic volume HR, (1.05 per 10 mL increase; <0.01) and extent of transmural late gadolinium enhancement (HR, 1.12; =0.04). Conclusions This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement-cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.
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http://dx.doi.org/10.1161/JAHA.120.019101DOI Listing
April 2021

Metabolomics in Severe Aortic Stenosis Reveals Intermediates of Nitric Oxide Synthesis as Most Distinctive Markers.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Amsterdam UMC, Vrije Universiteit Amsterdam, Physiology, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.

Background: Calcific aortic valve disease (CAVD) is a rapidly growing global health problem with an estimated 12.6 million cases globally in 2017 and a 112% increase of deaths since 1990 due to aging and population growth. CAVD may develop into aortic stenosis (AS) by progressive narrowing of the aortic valve. AS is underdiagnosed, and if treatment by aortic valve replacement (AVR) is delayed, this leads to poor recovery of cardiac function, absence of symptomatic improvement and marked increase of mortality. Considering the current limitations to define the stage of AS-induced cardiac remodeling, there is need for a novel method to aid in the diagnosis of AS and timing of intervention, which may be found in metabolomics profiling of patients.

Methods: Serum samples of nine healthy controls and 10 AS patients before and after AVR were analyzed by untargeted mass spectrometry. Multivariate modeling was performed to determine a metabolic profile of 30 serum metabolites which distinguishes AS patients from controls. Human cardiac microvascular endothelial cells (CMECs) were incubated with serum of the AS patients and then stained for ICAM-1 with Western Blot to analyze the effect of AS patient serum on endothelial cell activation.

Results: The top 30 metabolic profile strongly distinguishes AS patients from healthy controls and includes 17 metabolites related to nitric oxide metabolism and 12 metabolites related to inflammation, in line with the known pathomechanism for calcific aortic valve disease. Nine metabolites correlate strongly with left ventricular mass, of which three show reversal back to control values after AVR. Western blot analysis of CMECs incubated with AS patient sera shows a significant reduction (14%) in ICAM-1 in AS samples taken after AVR compared to AS patient sera before AVR.

Conclusion: Our study defined a top 30 metabolic profile with biological and clinical relevance, which may be used as blood biomarker to identify AS patients in need of cardiac surgery. Future studies are warranted in patients with mild-to-moderate AS to determine if these metabolites reflect disease severity and can be used to identify AS patients in need of cardiac surgery.
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http://dx.doi.org/10.3390/ijms22073569DOI Listing
March 2021

Altered left atrial 4D flow characteristics in patients with paroxysmal atrial fibrillation in the absence of apparent remodeling.

Sci Rep 2021 Mar 16;11(1):5965. Epub 2021 Mar 16.

Department of Cardiology, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age = 61 ± 8 years) and 5 age/gender matched controls (age = 56 ± 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained: flow velocity (mean, peak), stasis defined as the relative volume with velocities < 10 cm/s, and kinetic energy (KE). Furthermore, LA global strain values were derived from b-SSFP cine images using dedicated CMR feature-tracking software. Even in sinus rhythm, LA mean and peak flow velocities over the entire cardiac cycle were significantly lower in paroxysmal AF patients compared to controls [(13.1 ± 2.4 cm/s vs. 16.7 ± 2.1 cm/s, p = 0.01) and (19.3 ± 4.7 cm/s vs. 26.8 ± 5.5 cm/s, p = 0.02), respectively]. Moreover, paroxysmal AF patients expressed more stasis of blood than controls both in the LA (43.2 ± 10.8% vs. 27.8 ± 7.9%, p = 0.01) and in the LA appendage (73.3 ± 5.7% vs. 52.8 ± 16.2%, p = 0.04). With respect to energetics, paroxysmal AF patients demonstrated lower mean and peak KE values (indexed to maximum LA volume) than controls. No significant differences were observed for LA volume, function, and strain parameters between the groups. Global LA flow dynamics in paroxysmal AF patients appear to be impaired including mean/peak flow velocity, stasis fraction, and KE, partly independent of LA remodeling. This pathophysiological flow pattern may be of clinical value to explain the increased incidence of thromboembolic events in paroxysmal AF patients, in the absence of actual AF or LA remodeling.
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http://dx.doi.org/10.1038/s41598-021-85176-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966746PMC
March 2021

Characteristics and prognostic value of right ventricular (dys)function in patients with non-ischaemic dilated cardiomyopathy assessed with cardiac magnetic resonance imaging.

ESC Heart Fail 2021 Apr 9;8(2):1055-1063. Epub 2021 Feb 9.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.

Aims: In non-ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all-cause mortality and ventricular arrhythmias (VA) was evaluated.

Methods And Results: Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction < 50%) on CMR were included retrospectively. Left atrial (LA), LV, and RV volumes and function were quantified. RV systolic dysfunction was defined as RVEF<45%. The presence and pattern of late gadolinium enhancement (LGE) on CMR were assessed visually. Septal midwall LGE was defined as midmyocardial stripe-like or patchy hyperenhancement in the septal segments, and the extent was quantified using the full width at half maximum method. Primary endpoint was a composite of all-cause mortality and VA, including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter defibrillator therapy. Secondary endpoints were time to all-cause mortality alone and time to VA alone. A total of 216 DCM patients were included (42% female, age 58 ± 14 years). Mean RVEF was 46 ± 12%, and RV dysfunction was present in 38%. RVEF was moderately correlated with LA dilation (LA minimal volume ρ = -0.38, P < 0.001) and strongly correlated with LA and LV dysfunction (LA emptying fraction r = 0.58, P < 0.001 and LVEF ρ = 0.52, P < 0.001). Septal midwall LGE was more often observed in patients with RV dysfunction compared with patients with preserved RV function (respectively 40% vs. 26%, P = 0.04). No correlation was found between RVEF and the extent of septal midwall LGE (ρ = -0.12, P = 0.34). During a median follow-up of 2.2 years [IQR 1.6-2.8], 30 patients experienced the primary endpoint. RV dysfunction was significantly associated with shorter time to the composite primary endpoint (HR 3.19 [95% CI 1.49-6.84], P < 0.01) and to the secondary endpoint of VA alone (HR 6.48 [95% CI 1.83-22.98], P < 0.01). There was a trend towards increased mortality when RV dysfunction was present (HR 2.54 [95% CI 0.99-6.57], P = 0.05).

Conclusions: Right ventricular dysfunction was predominantly observed in patients with DCM with advanced heart failure and pronounced myocardial remodelling, defined as increased LV and LA dilation and dysfunction and the presence of septal midwall LGE on CMR. During follow-up, RV dysfunction was associated with shorter time to all-cause mortality and ventricular arrhythmic events.
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http://dx.doi.org/10.1002/ehf2.13072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006611PMC
April 2021

Regional myocardial function at preclinical disease stage of hypertrophic cardiomyopathy in female gene variant carriers.

Int J Cardiovasc Imaging 2021 Feb 9. Epub 2021 Feb 9.

Department of Physiology, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

We recently showed more severe diastolic dysfunction at the time of myectomy in female compared to male patients with obstructive hypertrophic cardiomyopathy. Early recognition of aberrant cardiac contracility using cardiovascular magnetic resonance (CMR) imaging may identify women at risk of cardiac dysfunction. To define myocardial function at an early disease stage, we studied regional cardiac function using CMR imaging with tissue tagging in asymptomatic female gene variant carriers. CMR imaging with tissue tagging was done in 13 MYBPC3, 11 MYH7 and 6 TNNT2 gene carriers and 16 age-matched controls. Regional peak circumferential strain was derived from tissue tagging images of the basal and midventricular segments of the septum and lateral wall. Left ventricular wall thickness and global function were comparable between MYBPC3, MYH7, TNNT2 carriers and controls. MYH7 gene variant carriers showed a different strain pattern as compared to the other groups, with higher septal peak circumferential strain at the basal segments compared to the lateral wall, whereas MYBPC3, TNNT2 carriers and controls showed higher strain at the lateral wall compared to the septum. Only subtle gene-specific changes in strain pattern occur in the myocardium preceding development of cardiac hypertrophy. Overall, our study shows that there are no major contractile deficits in asymptomatic females carrying a pathogenic gene variant, which would justify the use of CMR imaging for earlier diagnosis.
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http://dx.doi.org/10.1007/s10554-020-02156-1DOI Listing
February 2021

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

J Cardiovasc Magn Reson 2021 Jan 11;23(1). Epub 2021 Jan 11.

Department of Cardiology, Amsterdam Cardiovascular Sciences (ACS), Amsterdam University Medical Centers (AUMC), Location VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response.

Methods And Results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRS), systolic stretch index (SSI), and internal stretch factor (ISF) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESS) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESS to be independently related to LVESV change together with age and QRS.

Conclusion: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESS) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.
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http://dx.doi.org/10.1186/s12968-020-00701-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798189PMC
January 2021

Defining the prognostic value of [15O]H2O positron emission tomography-derived myocardial ischaemic burden.

Eur Heart J Cardiovasc Imaging 2020 Nov 17. Epub 2020 Nov 17.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.

Aims : Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB.

Methods And Results : A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P < 0.001] or low MFR IB [AER: 2.4% vs. 0.6%, P < 0.001]. Patients with a concordant high IB had the worst outcome (AER: 3.1%), whereas patients with a concordant low or discordant IB result had similar and low AERs of 0.5% and 0.9% (P = 0.953), respectively. Both thresholds were of prognostic value beyond clinical characteristics, however, only the hMBF IB threshold remained predictive when adjusted for clinical characteristics and combined use of the hMBF and MFR thresholds.

Conclusion : A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.
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http://dx.doi.org/10.1093/ehjci/jeaa305DOI Listing
November 2020

Left Ventricular Hypertrabeculation Is Not Associated With Cardiovascular Morbity or Mortality: Insights From the Eurocmr Registry.

Front Cardiovasc Med 2020 22;7:158. Epub 2020 Sep 22.

William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, United Kingdom.

Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry. We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3. Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis.
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http://dx.doi.org/10.3389/fcvm.2020.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536335PMC
September 2020

Hypertensive Exposure Markers by MRI in Relation to Cerebral Small Vessel Disease and Cognitive Impairment.

JACC Cardiovasc Imaging 2021 Jan 30;14(1):176-185. Epub 2020 Sep 30.

Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Science, Amsterdam, the Netherlands. Electronic address:

Objectives: This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD) and cognitive impairment, with the aim of understanding the role of hypertension in the early stages of deteriorating brain health.

Background: Preserving brain health into advanced age is one of the great challenges of modern medicine. Hypertension is thought to induce vascular brain injury through exposure of the cerebral microcirculation to increased pressure/pulsatility. Cardiovascular MRI provides markers of (subclinical) hypertensive exposure, such as aortic stiffness by pulse wave velocity (PWV), left ventricular (LV) mass index (LVMi), and concentricity by mass-to-volume ratio.

Methods: A total of 559 participants from the Heart-Brain Connection Study (431 patients with manifest cardiovascular disease and 128 control participants), age 67.8 ± 8.8 years, underwent 3.0-T heart-brain MRI and extensive neuropsychological testing. Aortic PWV, LVMi, and LV mass-to-volume ratio were evaluated in relation to presence of CSVD and cognitive impairment. Effect modification by patient group was investigated by interaction terms; results are reported pooled or stratified accordingly.

Results: Aortic PWV (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.05 to 1.30 in patient groups only), LVMi (in carotid occlusive disease, OR: 5.69; 95% CI: 1.63 to 19.87; in other groups, OR: 1.30; 95% CI: 1.05 to 1.62]) and LV mass-to-volume ratio (OR: 1.81; 95% CI: 1.46 to 2.24) were associated with CSVD. Aortic PWV (OR: 1.07; 95% CI: 1.02 to 1.13) and LV mass-to-volume ratio (OR: 1.27; 95% CI: 1.07 to 1.51) were also associated with cognitive impairment. Relations were independent of sociodemographic and cardiac index and mostly persisted after correction for systolic blood pressure or medical history of hypertension. Causal mediation analysis showed significant mediation by presence of CSVD in the relation between hypertensive exposure markers and cognitive impairment.

Conclusions: The extent of hypertensive exposure is associated with CSVD and cognitive impairment beyond clinical blood pressure or medical history. The mediating role of CSVD suggests that hypertension may lead to cognitive impairment through the occurrence of CSVD.
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http://dx.doi.org/10.1016/j.jcmg.2020.06.040DOI Listing
January 2021

Cerebral blood flow and cognitive functioning in patients with disorders along the heart-brain axis: Cerebral blood flow and the heart-brain axis.

Alzheimers Dement (N Y) 2020 12;6(1):e12034. Epub 2020 May 12.

Alzheimer Center Amsterdam Department of Neurology Amsterdam Neuroscience Amsterdam UMC VU University Medical Center Amsterdam the Netherlands.

Introduction: We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]).

Methods: We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi-center Heart-Brain Study. We used pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains.

Results: CBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning.

Discussion: We found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart-brain axis.
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http://dx.doi.org/10.1002/trc2.12034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507476PMC
May 2020

Incremental prognostic value of hybrid [15O]H2O positron emission tomography-computed tomography: combining myocardial blood flow, coronary stenosis severity, and high-risk plaque morphology.

Eur Heart J Cardiovasc Imaging 2020 10;21(10):1105-1113

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Aims: This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD).

Methods And Results: In this retrospective study, 539 patients referred for hybrid [15O]H2O PET-CT imaging because of suspected CAD were investigated. PET was used to determine myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenoses and high-risk plaque (HRP) morphology. Patients were followed up for the occurrence of all-cause death and non-fatal myocardial infarction (MI). During a median follow-up of 6.8 (interquartile range 4.8-7.8) years, 42 (7.8%) patients experienced events, including 23 (4.3%) deaths, and 19 (3.5%) MIs. Annualized event rates for normal vs. abnormal results of PET MBF, CCTA-derived stenosis, and HRP morphology were 0.6 vs. 2.1%, 0.4 vs. 2.1%, and 0.8 vs. 2.8%, respectively (P < 0.001 for all). Cox regression analysis demonstrated prognostic values of PET perfusion imaging [hazard ratio (HR) 3.75 (1.84-7.63), P < 0.001], CCTA-derived stenosis [HR 5.61 (2.36-13.34), P < 0.001], and HRPs [HR 3.37 (1.83-6.18), P < 0.001] for the occurrence of death or MI. However, only stenosis severity [HR 3.01 (1.06-8.54), P = 0.039] and HRPs [HR 1.93 (1.00-3.71), P = 0.049] remained independently associated.

Conclusion: PET-derived MBF, CCTA-derived stenosis severity, and HRP morphology were univariably associated with death and MI, whereas only stenosis severity and HRP morphology provided independent prognostic value.
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http://dx.doi.org/10.1093/ehjci/jeaa192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971168PMC
October 2020

On-Site Computed Tomography Versus Angiography Alone to Guide Coronary Stent Implantation: A Prospective Randomized Study.

J Invasive Cardiol 2020 Nov 10;32(11):E268-E276. Epub 2020 Sep 10.

Department of Interventional Cardiology and Angiology, National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland.

Objectives: The effect of intraprocedural coronary computed tomography angiography (coronary CTA) guidance on percutaneous coronary intervention (PCI) is unknown. We sought to determine the influence of CTA guidance on procedural strategies and immediate angiographic outcomes of PCI.

Methods: Sixty patients were randomized to CTA-guided PCI (29 patients, 36 lesions) or angiography-guided PCI (31 patients, 39 lesions). To enable hands-free manipulation of CTA images by the interventional cardiologist during PCI, we developed an onsite augmented-reality (AR) system comprising a mobile application and AR glass. The primary endpoints were defined as: (1) stent length; and (2) largest stent diameter according to compliance chart. Procedural strategies, two-dimensional (2D) and three-dimensional (3D) quantitative coronary angiography (QCA), and safety outcomes were compared.

Results: Whereas CTA guidance resulted in significantly higher frequency of stent postdilation using non-compliant (67% vs 31%; P<.01) and shorter balloons (16.6 ± 5.4 mm vs 20.5 ± 9.4 mm; P=.04) with numerically larger diameter (3.50 ± 0.63 mm vs 3.28 ± 0.45 mm; P=.10), it did not differ from angiography guidance with respect to lesion predilation, stent length, largest stent diameter according to compliance chart, and nominal stent diameter. The results of 2D- and 3D-QCA and safety outcomes were similar between groups. Neither death nor stroke occurred in either group.

Conclusions: PCI under intraprocedural CTA guidance is associated with similar stent size selection and more frequent stent postdilation, resulting in comparable immediate angiographic and safety outcomes as compared with PCI under angiographic guidance alone.
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November 2020

Non-invasive procedural planning using computed tomography-derived fractional flow reserve.

Catheter Cardiovasc Interv 2021 Mar 26;97(4):614-622. Epub 2020 Aug 26.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.

Objectives: This study aimed to investigate the performance of computed tomography derived fractional flow reserve based interactive planner (FFR planner) to predict the physiological benefits of percutaneous coronary intervention (PCI) as defined by invasive post-PCI FFR.

Background: Advances in FFR technology have enabled the simulation of hyperemic pressure changes after virtual removal of stenoses.

Methods: In 56 patients (63 vessels) invasive FFR measurements before and after PCI were obtained and FFR was calculated using pre-PCI coronary CT angiography. Subsequently, FFR and invasive coronary angiography models were aligned allowing virtual removal of coronary stenoses on pre-PCI FFR models in the same locations as PCI was performed. Relationships between invasive FFR and FFR , between post-PCI FFR and FFR planner, and between delta FFR and delta FFR were evaluated.

Results: Pre PCI, invasive FFR was 0.65 ± 0.12 and FFR was 0.64 ± 0.13 (p = .34) with a mean difference of 0.015 (95% CI: -0.23-0.26). Post-PCI invasive FFR was 0.89 ± 0.07 and FFR planner was 0.85 ± 0.07 (p < .001) with a mean difference of 0.040 (95% CI: -0.10-0.18). Delta invasive FFR and delta FFR were 0.23 ± 0.12 and 0.21 ± 0.12 (p = .09) with a mean difference of 0.025 (95% CI: -0.20-0.25). Significant correlations were found between pre-PCI FFR and FFR (r = 0.53, p < .001), between post-PCI FFR and FFR planner (r = 0.41, p = .001), and between delta FFR and delta FFR (r = 0.57, p < .001).

Conclusions: The non-invasive FFR planner tool demonstrated significant albeit modest agreement with post-PCI FFR and change in FFR values after PCI. The FFR planner tool may hold promise for PCI procedural planning; however, improvement in technology is warranted before clinical application.
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http://dx.doi.org/10.1002/ccd.29210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984343PMC
March 2021

Impact of local left atrial wall thickness on the incidence of acute pulmonary vein reconnection after Ablation Index-guided atrial fibrillation ablation.

Int J Cardiol Heart Vasc 2020 Aug 3;29:100574. Epub 2020 Jul 3.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences Amsterdam, the Netherlands.

Background: Although Ablation Index (AI)-guided ablation facilitates creation of lesions of consistent depth, pulmonary vein (PV) reconnection is still commonly observed after AI-guided pulmonary vein isolation (PVI). The present study aimed to investigate the impact of local left atrial wall thickness on the incidence of acute PV reconnection after AI-guided atrial fibrillation (AF) ablation.

Methods And Results: Seventy patients (63% paroxysmal AF, 67% male, mean age 63 ± 8 years) who underwent preprocedural CT imaging and AI-guided AF ablation were studied. Occurrence of acute PV reconnection after initial PVI was assessed after a 30-minute waiting period. Ablation procedures were retrospectively analyzed and each ablation circle was subdivided into 8 segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were determined for each segment. PV antrum wall thickness was assessed for each segment on reconstructed CT images based on patient-specific thresholds in Hounsfield Units. Acute reconnection occurred in 27/1120 segments (2%, 15 anterior/roof, 12 posterior/inferior) in 19/140 ablation circles (14%). Reconnected segments were characterized by a greater local atrial wall thickness, both in anterior/roof (1.87 ± 0.42 vs. 1.54 ± 0.42 mm; p < 0.01) and posterior/inferior (1.43 ± 0.20 vs. 1.16 ± 0.22 mm; p < 0.01) segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were not associated with acute reconnection.

Conclusions: Local atrial wall thickness is associated with acute pulmonary vein reconnection after AI-guided PVI. Individualized AI targets based on local wall thickness may be of use to create transmural ablation lesions and prevent PV reconnection after PVI.
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http://dx.doi.org/10.1016/j.ijcha.2020.100574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334811PMC
August 2020

Diagnostic value of comprehensive on-site and off-site coronary CT angiography for identifying hemodynamically obstructive coronary artery disease.

J Cardiovasc Comput Tomogr 2021 Jan-Feb;15(1):37-45. Epub 2020 Jun 9.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. Electronic address:

Background: This study aimed to investigate the diagnostic value of comprehensive on-site coronary computed tomography angiography (CCTA) using stenosis and plaque measures and subtended myocardial mass (V) for fractional flow reserve (FFR) defined hemodynamically obstructive coronary artery disease (CAD). Additionally, the incremental diagnostic value of off-site CT-derived FFR (FFR) was assessed.

Methods: Prospectively enrolled patients underwent CCTA followed by invasive FFR interrogation of all major coronary arteries. Vessels with ≥30% stenosis were included for analysis. On-site CCTA assessment included qualitative and quantitative stenosis (visual grading and minimal lumen area, MLA) and plaque measures (characteristics and volumes), and V. Diagnostic value of comprehensive on-site CCTA assessment was tested by comparing area under the curves (AUC). In vessels with available FFR, the incremental value of off-site FFR was tested.

Results: In 236 vessels (132 patients), MLA, positive remodeling, non-calcified plaque volume, and V were independent on-site CCTA predictors for hemodynamically obstructive CAD (p < 0.05 for all). V/MLA outperformed all these on-site CCTA parameters (AUC = 0.85) and V was incremental to all other CCTA predictors (p = 0.02). In subgroup analysis (n = 194 vessels), diagnostic performance of FFR and V/MLA was similar (AUC 0.89 and 0.85 respectively, p = 0.25). Furthermore, diagnostic performance significantly albeit minimally increased when FFR was added to on-site CCTA assessment (ΔAUC = 0.03, p = 0.02).

Conclusions: In comprehensive on-site CCTA assessment, V/MLA2 demonstrated greatest diagnostic value for hemodynamically obstructive CAD and V was incremental to all evaluated CCTA indices. Additionally, adding FFR only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to FFR.
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http://dx.doi.org/10.1016/j.jcct.2020.05.002DOI Listing
April 2021

Differences between gap-related persistent conduction and carina-related persistent conduction during radiofrequency pulmonary vein isolation.

J Cardiovasc Electrophysiol 2020 07 22;31(7):1616-1627. Epub 2020 May 22.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: During pulmonary vein isolation (PVI), nonisolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the wide-area circumferential ablation (WACA) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap-related persistent conduction (gap-RPC) and carina-related persistent conduction (carina-RPC) during PVI.

Methods And Results: Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62 ± 9 years) undergoing first contact force-guided radiofrequency PVI were studied. Preprocedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap-RPC or carina-RPC, depending on the earliest activation site. The 1-year AF recurrence rate was higher in patients with gap-RPC (47%) compared to patients without gap-RPC (28%; P = .003). No significant difference in 1-year recurrence rate was found between patients with carina-RPC (37%) and patients without carina-RPC (31%; P = .379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap-RPC, whereas carina width and WACA circumference correlated with carina-RPC.

Conclusions: Gap-RPC is associated with increased AF recurrence risk after PVI, whereas carina-RPC does not predict AF recurrence. Moreover, gap-RPC and carina-RPC have different correlates and may thus have different underlying mechanisms.
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http://dx.doi.org/10.1111/jce.14544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383882PMC
July 2020

Comparison Between the Performance of Quantitative Flow Ratio and Perfusion Imaging for Diagnosing Myocardial Ischemia.

JACC Cardiovasc Imaging 2020 09 15;13(9):1976-1985. Epub 2020 Apr 15.

Department of Cardiology Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address:

Objectives: This study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)-defined coronary artery disease (CAD).

Background: QFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking.

Methods: A total of 208 (624 vessels) patients underwent technetium-m tetrofosmin SPECT and [O]HO PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels).

Results: QFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively.

Conclusions: In this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFR-defined significant CAD compared with perfusion imaging by SPECT or PET.
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http://dx.doi.org/10.1016/j.jcmg.2020.02.012DOI Listing
September 2020

Value of CMR and PET in Predicting Ventricular Arrhythmias in Ischemic Cardiomyopathy Patients Eligible for ICD.

JACC Cardiovasc Imaging 2020 08 15;13(8):1755-1766. Epub 2020 Apr 15.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. Electronic address:

Objectives: This study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs).

Background: Improved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking.

Methods: Seventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [O]HO and [C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated.

Results: In total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA.

Conclusions: In patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.
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http://dx.doi.org/10.1016/j.jcmg.2020.01.026DOI Listing
August 2020

Increased Myocardial Oxygen Consumption Precedes Contractile Dysfunction in Hypertrophic Cardiomyopathy Caused by Pathogenic Gene Variants.

J Am Heart Assoc 2020 04 15;9(8):e015316. Epub 2020 Apr 15.

Department of Physiology Amsterdam University Medical Center Amsterdam Cardiovascular Sciences Vrije Universiteit University Medical Center Amsterdam Amsterdam the Netherlands.

Background Hypertrophic cardiomyopathy is caused by pathogenic sarcomere gene variants. Individuals with a thin-filament variant present with milder hypertrophy than carriers of thick-filament variants, although prognosis is poorer. Herein, we defined if decreased energetic status of the heart is an early pathomechanism in (troponin T gene) variant carriers. Methods and Results Fourteen individuals with variants (genotype positive), without left ventricular hypertrophy (G+/LVH-; n=6) and with LVH (G+/LVH+; n=8) and 14 healthy controls were included. All participants underwent cardiac magnetic resonance and [C]-acetate positron emission tomography imaging to assess LV myocardial oxygen consumption, contractile parameters and myocardial external efficiency. Cardiac efficiency was significantly reduced compared with controls in G+/LVH- and G+/LVH+. Lower myocardial external efficiency in G+/LVH- is explained by higher global and regional oxygen consumption compared with controls without changes in contractile parameters. Reduced myocardial external efficiency in G+/LVH+ is explained by the increase in LV mass and higher oxygen consumption. Septal oxygen consumption was significantly lower in G+/LVH+ compared with G+/LVH-. Although LV ejection fraction was higher in G+/LVH+, both systolic and diastolic strain parameters were lower compared with controls, which was most evident in the hypertrophied septal wall. Conclusions Using cardiac magnetic resonance and [C]-acetate positron emission tomography imaging, we show that G+/LVH- have an initial increase in oxygen consumption preceding contractile dysfunction and cardiac hypertrophy, followed by a decline in oxygen consumption in G+/LVH+. This suggests that high oxygen consumption and reduced myocardial external efficiency characterize the early gene variant-mediated disease mechanisms that may be used for early diagnosis and development of preventive treatments.
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http://dx.doi.org/10.1161/JAHA.119.015316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428531PMC
April 2020

Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.

N Engl J Med 2020 03;382(12):1180

Amsterdam University Medical Centers, Amsterdam, the Netherlands

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http://dx.doi.org/10.1056/NEJMc2000284DOI Listing
March 2020

The relevance of a multidomain geriatric assessment in older patients with heart failure.

ESC Heart Fail 2020 06 3;7(3):1264-1272. Epub 2020 Mar 3.

Department of Internal Medicine and Geriatrics, Amsterdam UMC, location VUmc, Amsterdam Cardiovascular Sciences, Boelelaan 1117, 1081, HV, Amsterdam, The Netherlands.

Aims: Physical frailty screening is more commonly performed at outpatient heart failure (HF) clinics. However, this does not incorporate other common geriatric domains. This study assesses whether a multidomain geriatric assessment, in comparison with HF severity or physical frailty, is associated with short-term adverse outcomes.

Methods And Results: This is a prospective cohort study of 197 patients with HF (mean age 78, 44% female) attending outpatient HF clinics. HF severity was assessed with New York Heart Association class (I-II versus III-IV) and N-terminal pro b-type natriuretic peptide levels. Physical frailty was assessed with the Fried frailty criteria (not frail, pre-frail, and frail). The following geriatric domains were assessed: physical function, nutrition, polypharmacy, cognition, and dependency in activities of daily living. Logistic regression analyses adjusted for age, sex, diabetes and kidney function assessed 3 month risk of adverse health outcomes (emergency department visits, hospital admissions, and/or death) according to HF severity, physical frailty, and number of affected domains. Number (%) of patients with HF with no, 1, 2, and ≥3 domains affected were 36 (18%), 61 (31%), 58 (29%), and 42 (21%). Seventy-four adverse outcomes were experienced in 50 patients at follow-up. Severity of HF and physical frailty were not significantly associated with an increased risk of adverse health outcomes. However, increasing number of affected domains were significantly associated with an increased risk of adverse outcomes. Compared with no domains affected, odds ratios (95% confidence interval) for 1, 2, and ≥3 domains were 1.8 (0.5-6.5), 4.5 (1.3-15.4), and 7.2 (2.0-26.3) (P-trend <0.01). Further adjustment for HF severity and frailty status slightly attenuated the effect estimates (P-trend 0.02).

Conclusions: Having limitations in multiple domains appears more strongly associated with short-term adverse outcomes than HF severity and physical frailty. This may illustrate the potential added value of a multidomain geriatric assessment in the evaluation and treatment of patients with HF with respect to relevant short-term health outcomes.
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http://dx.doi.org/10.1002/ehf2.12651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261545PMC
June 2020

Coronary collaterals and myocardial viability in patients with chronic total occlusions.

EuroIntervention 2020 Aug 7;16(6):e453-e461. Epub 2020 Aug 7.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Aims: This study aimed to evaluate associations between coronary collaterals and myocardial viability as assessed by quantitative cardiac magnetic resonance (CMR) imaging in patients with a chronic coronary total occlusion (CTO).

Methods And Results: A total of 218 patients with a CTO who underwent CMR between 2013 and 2018 were included. A concomitant collateral connection (CC) score 2 and Rentrop grade 3 defined well-developed collaterals in 146 (67%) patients, whereas lower CC scores or Rentrop grades characterised poorly developed collaterals. Dysfunctional myocardium (<3 mm segmental wall thickening [SWT]) and ≤50% late gadolinium enhancement (LGE) defined viability. Extensive scar (LGE >50%) was observed in only 5% of CTO segments. In the CTO territory, SWT was greater (3.72±1.51 vs 3.05±1.60 mm, p<0.01) and the extent of scar was less (7.0 [0.1-16.7] vs 13.1% [2.8-22.2], p=0.048) in patients having well-developed versus poorly developed collaterals. Viability was more prevalent in CTO segments among patients with poorly developed versus well-developed collaterals (44% vs 30% of segments, p<0.01), predominantly due to a higher prevalence of dysfunctional myocardium (51% vs 34% of segments, p<0.01) in the poorly developed collateral group.

Conclusions: The infarcted area in myocardium subtended by a CTO is generally limited. Well-developed collaterals are associated with less myocardial scar and enhanced preserved function. However, viability was regularly present in patients with poorly developed collaterals. Visual summary. CMR-derived viability with potential for functional recovery is regularly present in myocardium supplied by poorly developed collaterals in patients with a CTO.
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http://dx.doi.org/10.4244/EIJ-D-19-01006DOI Listing
August 2020

Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial.

J Am Heart Assoc 2020 03 3;9(5):e014411. Epub 2020 Mar 3.

Department of Cardiology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam Cardiovascular Sciences Amsterdam the Netherlands.

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements including calculation of the reactive hyperemia index and clinical follow-up were obtained up to 1.5 years. Major adverse clinical events and bleedings were scored. An intention to treat and a per-protocol analysis were performed. There were no between-group differences in platelet inhibition and endothelial function. At 1 year the reactive hyperemia index in the ticagrelor group was 0.66±0.26 versus 0.61±0.28 in the prasugrel group (=0.31). Platelet inhibition was lower at 1 month versus 1 year in the total study population (61% [42%-81%] versus 83% [61%-95%]; <0.001), and per-protocol platelet inhibition was higher in patients randomized to ticagrelor versus prasugrel at 1 year (91% [83%-97%] versus 82% [65%-92%]; =0.002). There was an improvement in intention to treat endothelial function in patients randomized to ticagrelor (=0.03) but not in patients randomized to prasugrel (=0.88). Major adverse clinical events (10% versus 14%; =0.54) and bleedings (47% versus 63%; =0.10) were similar in the intention-to-treat analysis in both groups. Conclusions Platelet inhibition at 1 year was higher in the ticagrelor group, without an accompanying increase in bleedings. Endothelial function improved over time in ticagrelor patients, while it did not change in the prasugrel group. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02422888.
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http://dx.doi.org/10.1161/JAHA.119.014411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335553PMC
March 2020

Correlation between septal midwall late gadolinium enhancement on CMR and conduction delay on ECG in patients with nonischemic dilated cardiomyopathy.

Int J Cardiol Heart Vasc 2020 Feb 25;26:100474. Epub 2020 Jan 25.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Cardiology, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.

Background: Septal midwall late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is a characteristic finding in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse cardiac events. QRS-prolongation in DCM is also frequently present and a predictor of arrhythmic events and mortality. Since the His-Purkinje fibres are located in the interventricular septum, QRS-prolongation may directly result from septal fibrosis, visualized by LGE. Our aim was to study the correlation of the presence and extent of septal midwall LGE and QRS-duration.

Methods: DCM-patients with left ventricular (LV) dysfunction (LVEF < 50%) were included. LV volumes, systolic function and nonischemic septal midwall LGE, defined as patchy or stripe-like LGE in the septal segments, were quantified. QRS-duration on standard 12-lead ECG was measured.

Results: 165 DCM-patients were included (62% male, mean age 59 ± 15 years) with a median LVEF of 36% [24-44]. Fifty-one patients (31%) demonstrated septal midwall LGE with a median extent of 8.1 gram [4.3-16.8]. Patients with midwall LGE had increased LV end-diastolic volumes (EDV) 248 mL [193-301] vs. 193 mL [160-239], p < 0.001) and lower LVEF (26% [18-35] vs. 40% [32-45], p < 0.001). Median QRS-duration was 110 ms [95-146] without a correlation to the presence nor extent of midwall LGE. QRS-duration was moderately correlated with LV-dilation and mass (respectively r = 0.35, p < 0.001 and r = 0.30, p < 0.001).

Conclusion: In DCM-patients, QRS-prolongation and septal midwall LGE are frequently present and often co-exist. However, they are not correlated. This suggests that the assessment of LGE-CMR has complementary value to ECG evaluation in the clinical assessment and risk stratification of DCM-patients.
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http://dx.doi.org/10.1016/j.ijcha.2020.100474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994302PMC
February 2020

Left atrial sphericity as a marker of atrial remodeling: Comparison of atrial fibrillation patients and controls.

Int J Cardiol 2020 04 22;304:69-74. Epub 2020 Jan 22.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. Electronic address:

Background: Left atrial (LA) sphericity has been proposed as a more sensitive marker of atrial fibrillation (AF)-associated atrial remodeling compared to traditional markers such as LA size. However, mechanisms that underlie changes in LA sphericity are not fully understood and studies investigating the predictive value of LA sphericity for AF ablation outcome have yielded conflicting results. The present study aimed to assess correlates of LA sphericity and to compare LA sphericity in subjects with and without AF.

Methods: Measures of LA size (LA diameter, LA volume, LA volume index), LA sphericity and thoracic anteroposterior diameter (APd) at the level of the LA were determined using computed tomography (CT) imaging data in 293 AF patients (62% paroxysmal AF) and 110 controls.

Results: LA diameter (40.1 ± 6.8 mm vs. 35.2 ± 5.1 mm; p < 0.001), LA volume (116.0 ± 33.0 ml vs. 80.3 ± 22.6 ml; p < 0.001) and LA volume index (56.1 ± 15.3 ml/m vs. 41.6 ± 11.1 ml/m; p < 0.001) were significantly larger in AF patients compared to controls, also after adjustment for covariates. LA sphericity did not differ between AF patients and controls (83.7 ± 2.9 vs. 83.9 ± 2.4; p = 0.642). Multivariable linear regression analysis demonstrated that LA diameter, LA volume, female sex, body length and thoracic APd were independently associated with LA sphericity.

Conclusions: The present study suggests that thoracic constraints rather than the presence of AF determine LA sphericity, implying LA sphericity to be unsuitable as a marker of AF-related atrial remodeling.
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http://dx.doi.org/10.1016/j.ijcard.2020.01.042DOI Listing
April 2020

Comparison between quantitative cardiac magnetic resonance perfusion imaging and [O]HO positron emission tomography.

Eur J Nucl Med Mol Imaging 2020 07 10;47(7):1688-1697. Epub 2019 Dec 10.

Department of Cardiology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands.

Purpose: To compare cardiac magnetic resonance imaging (CMR) with [O]HO positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD).

Methods: Fifty-nine patients with stable CAD underwent CMR and [O]HO PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress.

Results: CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P < 0.001 for stress MBF and r = 0.36; P < 0.001 for MFR). Bland-Altman analysis revealed a significant bias of 0.2 ± 1.0 mL/min/g for stress MBF and - 0.5 ± 1.2 for MFR. CMR-derived stress MBF and MFR demonstrated area under the curves of respectively 0.72 (95% CI: 0.65 to 0.79) and 0.76 (95% CI: 0.69 to 0.83) and had optimal cutoff values of 2.35 mL/min/g and 2.25 for detecting abnormal myocardial perfusion, defined as [O]HO PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR.

Conclusion: CMR measurements of stress MBF and MFR showed modest agreement to those obtained with [O]HO PET. Nevertheless, stress MBF and MFR were concordant between CMR and [O]HO PET in 77% and 80% of vascular territories, respectively.
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http://dx.doi.org/10.1007/s00259-019-04641-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248026PMC
July 2020

Frequent Cognitive Impairment in Patients With Disorders Along the Heart-Brain Axis.

Stroke 2019 12 5;50(12):3369-3375. Epub 2019 Nov 5.

From the Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience (A.M.H., A.E.L., W.M.v.d.F.), Amsterdam UMC, location VUmc, the Netherlands.

Background and Purpose- Patients with cardiovascular disease are at increased risk for cognitive decline. We studied the occurrence and profile of cognitive impairment in 3 patient groups as exemplar conditions of hemodynamic disturbances at different levels of the heart-brain axis, including patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (possible vascular cognitive impairment [VCI]). Methods- In 555 participants (160 HF, 107 COD, 160 possible VCI, 128 reference participants; 68±9 years; 36% F; Mini-Mental State Examination 28±2), we assessed cognitive functioning with a comprehensive test battery. Test scores were transformed into -scores. Compound -scores were constructed for: memory, language, attention/psychomotor speed, executive functioning, and global cognitive functioning. We rated cognitive domains as impaired when -score≤-1.5. Based on the number of impaired domains, patients were classified as cognitively normal, minor, or major cognitive impairment. We used general linear models and χ tests to compare cognitive functioning between patient groups and the reference group. Results- Age, sex, and education adjusted global cognitive functioning z-score was lower in patients with COD (β [SE]=-0.46 [0.10], <0.001) and possible VCI (β [SE]=-0.80 [0.09], <0.001) compared with reference participants. On all domains, -scores were lower in patients with COD and possible VCI compared with reference participants. Patients with HF had lower z-scores on attention/speed and language compared with reference participants. Cognitive impairment was observed in 18% of HF, 36% of COD, and 45% possible VCI. There was no difference in profile of impaired cognitive domains between patient groups. Memory and attention-psychomotor speed were most commonly affected, followed by executive functioning and language. Conclusions- A substantial part of patients with HF and COD had cognitive impairment, which warrants vigilance for the occurrence of cognitive impairment. These results underline the importance of an integrative approach in medicine in patients presenting with disorders in the heart-brain axis.
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http://dx.doi.org/10.1161/STROKEAHA.119.026031DOI Listing
December 2019

Impact of Specific Crossing Techniques in Chronic Total Occlusion Percutaneous Coronary Intervention on Recovery of Absolute Myocardial Perfusion.

Circ Cardiovasc Interv 2019 11 1;12(11):e008064. Epub 2019 Nov 1.

Department of Cardiology (S.P.S., W.J.S., R.S.D., P.A.v.D., M.J.B., H.E., M.K., A.C.v.R., A.N., P.K.), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Background: Multiple crossing techniques in chronic total occlusion (CTO) percutaneous coronary intervention have been developed. This study compared recovery of quantitative myocardial blood flow (MBF) after different CTO percutaneous coronary intervention techniques.

Methods: Consecutive patients with [O]HO positron emission tomography perfusion imaging before and 3 months after successful CTO percutaneous coronary intervention between 2013 and 2018 were included. Changes in hyperemic MBF, coronary flow reserve, and perfusion defect size were compared between antegrade wire escalation, retrograde wire escalation, antegrade dissection and reentry (ADR), and retrograde dissection and reentry.

Results: One hundred ninety-three patients were treated with antegrade wire escalation (N=90), retrograde wire escalation (N=24), ADR (N=35), and retrograde dissection and reentry (N=44). Increase in hyperemic MBF (1.19±0.77, 0.94±0.65, 1.09±0.63, and 1.02±0.75 mL·min·g, respectively; =0.40) and coronary flow reserve (1.34±1.08, 1.14±1.09, 1.31±0.96, and 1.24±0.99, respectively; =0.84) and decrease in defect size (3.2±2.1, 3.0±2.2, 2.7±2.1, and 2.9±1.9 segments, respectively; =0.77) were comparable between the 4 approaches. In addition, recovery of hyperemic MBF was less pronounced after subintimal crossing with knuckle-wire-technique compared with CrossBoss in controlled ADR and retrograde dissection and reentry (0.93±0.69 versus 1.54±0.65 mL·min·g, =0.02), and less after reentry using subintimal tracking and reentry in ADR compared with controlled ADR (Stingray) or limited antegrade subintimal tracking (0.60±0.53 versus 1.18±0.54 [=0.04] and versus 1.49±0.57 mL·min·g, [<0.01]).

Conclusions: Recovery of hyperemic MBF, coronary flow reserve, and perfusion defect size after CTO percutaneous coronary intervention was comparable between different approaches. Although sometimes necessary to cross a complex CTO lesion, subintimal knuckle wiring and subintimal tracking and reentry resulted in less hyperemic MBF improvement compared with other subintimal crossing and reentry techniques.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008064DOI Listing
November 2019

Prognostic value of [15O]H2O positron emission tomography-derived global and regional myocardial perfusion.

Eur Heart J Cardiovasc Imaging 2020 07;21(7):777-786

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1118, 1081 HZ Amsterdam, the Netherlands.

Aims: To evaluate the prognostic value of global and regional quantitative [15O]H2O positron emission tomography (PET) perfusion.

Methods And Results: In this retrospective study, 648 patients with suspected or known coronary artery disease (CAD) who underwent [15O]H2O PET were followed for the occurrence of death and myocardial infarction (MI). Global and regional hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) were obtained from [15O]H2O PET. During median follow-up of 6.9 (5.0-7.9) years, 64 (9.9%) patients experienced the composite of death (36-5.6%) and MI (28-4.3%). Impaired global hMBF (<2.65 mL/min/g) and CFR (<2.88) were both significant prognostic factors for death/MI after adjusting for clinical characteristics (both P < 0.001). However, after adjusting for clinical parameters and the combined use of hMBF and CFR, only hMBF remained an independent prognostic factor (P = 0.04). For regional perfusion, both impaired hMBF (<2.10 mL/min/g) and CFR (<2.07) demonstrated prognostic value for events (both P < 0.001). Similarly, after adjusting for clinical characteristics and combined use of hMBF and CFR, only hMBF had independent prognostic value (P = 0.04). The combination of global and regional perfusion did not improve prognostic performance over either global (P = 0.55) or regional perfusion (P = 0.37) alone.

Conclusion: Global and regional hMBF and CFR were all prognostic factors for death and MI. However, for both global and regional perfusion, hMBF remained the only independent prognostic factor after adjusting for the combined use of hMBF and CFR. Additionally, integrating global and regional perfusion did not increase prognostic performance compared to either regional or global perfusion alone.
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http://dx.doi.org/10.1093/ehjci/jez258DOI Listing
July 2020