Journal: Circ Cardiovasc Imaging

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Abstract

Prognostic Importance of Right Ventricular-Vascular Uncoupling in Acute Decompensated Heart Failure With Preserved Ejection Fraction.

Nakagawa A, Yasumura Y, Yoshida C, Okumura T, ... Hikoso S, Sakata Y
Background
Recent accumulating evidence reveals that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcome in patients with heart failure (HF), RV dysfunction, and pulmonary hypertension. However, the prognostic utility of RV-PA uncoupling in HF with preserved ejection fraction (HFpEF) remains elusive. In this study, we aim to investigate the associations of RV-PA uncoupling with outcomes of HFpEF inpatients.
Methods
We prospectively studied 655 patients, registered in PURSUIT-HFpEF (The Prospective Multicenter Obervational Study of Patients with Heart Failure with Preserved Ejection Fraction), a multicenter observational study of Japanese HFpEF inpatients. We assigned registered patients based on the determined value of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio that can predict primary outcome as an indicator of RV-PA uncoupling.
Results
Univariable Cox regression testing revealed that RV-PA uncoupling was associated with the primary endpoint of all-cause death, HF rehospitalization, and cerebrovascular events (hazard ratio [HR] 1.77 [95% CI, 1.34-2.32], <0.0001) and the secondary endpoints of all-cause death and HF rehospitalization (HR 2.75 [95% CI, 1.77-4.33], <0.0001, HR 1.63 [95% CI, 1.18-2.26], =0.0036, respectively). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with primary endpoint and all-cause death independent of age, sex, atrial fibrillation, renal dysfunction, elevated E/e\', and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) (HR 1.38 [95% CI, 1.01-1.88], =0.0413, HR 1.85 [95% CI, 1.14-3.01], =0.0129, respectively).
Conclusions
Prospective study of a hospitalized cohort revealed that RV-PA uncoupling was independently associated with adverse outcomes in acute decompensated patients with HFpEF. Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.



Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011430
Nakagawa A, Yasumura Y, Yoshida C, Okumura T, ... Hikoso S, Sakata Y
Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011430 | PMID: 33198494
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Abstract

Fibroblast Growth Factor 23 and Long-Term Cardiac Function: The Multi-Ethnic Study of Atherosclerosis.

Patel RB, Ning H, de Boer IH, Kestenbaum B, ... Shah SJ, Lloyd-Jones DM
Background
Although FGF23 (fibroblast growth factor 23) is associated with heart failure and atrial fibrillation, the mechanisms driving these associations are unclear. Sensitive measures of cardiovascular structure and function may provide mechanistic insight behind the associations of FGF23 with various cardiovascular diseases.
Methods
In MESA (the Multi-Ethnic Study of Atherosclerosis), we evaluated the associations of baseline serum FGF23 (2000-2002) with measures of left ventricular (LV) and left atrial mechanical function on cardiac magnetic resonance at 10-year follow-up (2010-2012).
Results
Of 2276 participants with available FGF23 and cardiac magnetic resonance at 10-year follow-up, participants with higher FGF23 levels were more likely White race, taking antihypertensive medications, and had lower kidney function. After covariate adjustment, FGF23 was associated with higher LV mass (β coefficient per 1 SD higher, 1.14 [95% CI, 0.16-2.12], =0.02), worse LV global circumferential strain (β coefficient per 1 SD higher, 0.15 [95% CI, 0.05-0.25], =0.003), worse LV midwall circumferential strain (β coefficient per 1 SD higher, 0.20 [95% CI, 0.08-0.31], =0.001), and lower left atrial total emptying fraction (β coefficient per 1 SD higher, -0.52 [95% CI, -1.02 to -0.02], =0.04). These associations were consistent across racial/ethnic groups and the spectrum of glomerular filtration rates. FGF23 was not associated with the presence of myocardial scar (odds ratio per 1 SD higher, 1.12 [95% CI, 0.86-1.45], =0.42).
Conclusions
In a multiethnic, community-based cohort, baseline FGF23 levels were independently associated with higher LV mass, lower LV systolic function, and reduced left atrial function over long-term follow-up. These findings provide potential mechanistic insight into associations of FGF23 with incident heart failure and atrial fibrillation.



Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011925
Patel RB, Ning H, de Boer IH, Kestenbaum B, ... Shah SJ, Lloyd-Jones DM
Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011925 | PMID: 33161733
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Abstract

Noninvasive Echocardiographic Left Ventricular Stroke Work Index Predicts Mortality in Cardiac Intensive Care Unit Patients.

Jentzer JC, Anavekar NS, Burstein BJ, Borlaug BA, Oh JK
Background
Reduced left ventricular stroke work index (LVSWI) has been associated with adverse outcomes in several populations of patients with chronic heart disease, but no prior studies have examined this metric in cardiac intensive care unit (CICU) patients. We sought to determine whether a low LVSWI, as measured noninvasively using transthoracic echocardiography, is associated with higher mortality in CICU patients.
Methods
Using a database of unique Mayo Clinic CICU admissions from 2007 to 2018, we identified patients with LVSWI measured by transthoracic echocardiography within 1 day of CICU admission. Hospital mortality was analyzed using multivariable logistic regression, and 1-year mortality was analyzed using multivariable Cox proportional-hazards analysis, adjusted for left ventricular ejection fraction and known predictors of hospital mortality.
Results
We included 4536 patients with a mean age of 68±14 years (36% women). Admission diagnoses (not mutually exclusive) included acute coronary syndrome in 62%, heart failure in 46%, and cardiogenic shock in 11%. The mean LVSWI was 38±14 g×min/m, and in-hospital mortality occurred in 6% of patients. LVSWI had better discrimination for hospital mortality than left ventricular ejection fraction (<0.001 by De Long test). Higher LVSWI was associated with lower in-hospital mortality (adjusted odds ratio, 0.72 per 10 g×min/m higher [95% CI, 0.61-0.84]; <0.001) and lower 1-year mortality (adjusted hazard ratio, 0.812 per 1 g×min/m higher [95% CI, 0.759-0.868]; <0.001). Stepwise decreases in hospital and 1-year mortality were observed with higher LVSWI.
Conclusions
Low LVSWI, reflecting poor left ventricular systolic and diastolic performance, is associated with increased short-term and long-term mortality among CICU patients. This emphasizes the importance of Doppler transthoracic echocardiography as a predictor of outcomes among critically ill patients. Further study is required to determine whether early interventions to optimize LVSWI can improve outcomes in the CICU setting.



Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011642
Jentzer JC, Anavekar NS, Burstein BJ, Borlaug BA, Oh JK
Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011642 | PMID: 33190537
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Abstract

Left Ventricular Magnetic Resonance Imaging Strain Predicts the Onset of Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

Siddiqui S, Alsaied T, Henson SE, Gandhi J, ... Lang SM, Taylor MD
Background
Early detection of left ventricular (LV) dysfunction before the onset of overt Duchenne muscular dystrophy-associated cardiomyopathy (DMDAC) may direct clinical management to slow onset of dysfunction. We aimed to assess whether LV strain will predict those who develop DMDAC.
Methods
We performed a single center retrospective case control study of patients with Duchenne muscular dystrophy who underwent serial cardiac magnetic resonance between 2006 and 2019. Patients with Duchenne muscular dystrophy with an LV ejection fraction ≥55% on ≥1 cardiac magnetic resonance were identified and grouped into age-matched +DMDAC and -DMDAC. Within 3 years, +DMDAC had a subsequent cardiac magnetic resonance with a decline in LV ejection fraction ≥10% and absolute LV ejection fraction ≤50%. -DMDAC maintained an LV ejection fraction ≥55% on serial cardiac magnetic resonances. Two-dimensional and 3-dimensional global radial strain, global circumferential strain (GCS), and global longitudinal strain were measured using tissue tracking software and their ability to predict DMDAC onset was assessed. Multivariable analysis adjusted for late gadolinium enhancement.
Results
Thirty +DMDAC and 30 age-matched -DMDAC patients were included with a total of 164 studies analyzed. Before DMDAC onset, 2-dimensional global radial strain and GCS were significantly worse in +DMDAC compared with -DMDAC (25.1±6.0 versus 29.0±6.3, =0.011; -15.4%±2.4 versus -17.3%±2.6, =0.003). Three-dimensional GCS and global radial strain had similar findings. Among strain measures, 3-dimensional GCS had the highest area under the curve to predict DMDAC in our cohort. These findings persisted after adjusting for the presence of late gadolinium enhancement.
Conclusions
Reduced global radial strain and GCS may predict those at risk for developing DMDAC before onset of LV dysfunction and its clinical utility warrants further exploration.



Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011526
Siddiqui S, Alsaied T, Henson SE, Gandhi J, ... Lang SM, Taylor MD
Circ Cardiovasc Imaging: 30 Oct 2020; 13:e011526 | PMID: 33190531
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Abstract

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor Cu-Macrin in Mice, Rabbits, and Pigs.

Nahrendorf M, Hoyer FF, Meerwaldt AE, van Leent MMT, ... Weissleder R, Mulder WJM
Background
Macrophages, innate immune cells that reside in all organs, defend the host against infection and injury. In the heart and vasculature, inflammatory macrophages also enhance tissue damage and propel cardiovascular diseases.
Methods
We here use in vivo positron emission tomography (PET) imaging, flow cytometry, and confocal microscopy to evaluate quantitative noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer Cu-Macrin-a 20-nm spherical dextran nanoparticle assembled from nontoxic polyglucose.
Results
PET imaging using Cu-Macrin faithfully reported accumulation of macrophages in the heart and lung of mice with myocardial infarction, sepsis, or pneumonia. Flow cytometry and confocal microscopy detected the near-infrared fluorescent version of the nanoparticle (Macrin) primarily in tissue macrophages. In 5-day-old mice, Cu-Macrin PET imaging quantified physiologically more numerous cardiac macrophages. Upon intravenous administration of Cu-Macrin in rabbits and pigs, we detected heightened macrophage numbers in the infarcted myocardium, inflamed lung regions, and atherosclerotic plaques using a clinical PET/magnetic resonance imaging scanner. Toxicity studies in rats and human dosimetry estimates suggest that Cu-Macrin is safe for use in humans.
Conclusions
Taken together, these results indicate Cu-Macrin could serve as a facile PET nanotracer to survey spatiotemporal macrophage dynamics during various physiological and pathological conditions. Cu-Macrin PET imaging could stage inflammatory cardiovascular disease activity, assist disease management, and serve as an imaging biomarker for emerging macrophage-targeted therapeutics.



Circ Cardiovasc Imaging: 29 Sep 2020; 13:e010586
Nahrendorf M, Hoyer FF, Meerwaldt AE, van Leent MMT, ... Weissleder R, Mulder WJM
Circ Cardiovasc Imaging: 29 Sep 2020; 13:e010586 | PMID: 33076700
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Abstract

Dimensionless Index in Patients With Low-Gradient Severe Aortic Stenosis and Preserved Ejection Fraction.

Altes A, Thellier N, Rusinaru D, Marsou W, ... Tribouilloy C, Maréchaux S

Background Risk stratification of patients with low-gradient (LG) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction remains challenging. We sought to evaluate the relationship between the dimensionless index (DI)-the ratio of the left ventricular outflow tract time-velocity integral to that of the aortic valve jet-and mortality in these patients. Methods Seven hundred fifty-five patients with LG severe AS (defined by aortic valve area ≤1 cm or aortic valve area indexed to body surface area ≤0.6 cm/m and mean aortic pressure gradient <40 mm Hg) and preserved left ventricular ejection fraction ≥50% were studied. Flow status was defined according to stroke volume index <35 mL/m (low flow, LF) or ≥35 mL/m (normal flow, NF). Results After adjustment for age, sex, body mass index, Charlson comorbidity index, history of hypertension, history of atrial fibrillation, AS-related symptoms, left ventricular ejection fraction, indexed left ventricular ventricular mass, aortic valve area, and aortic valve replacement as a time-dependent covariate, patients with LG-LF and DI<0.25 exhibited a considerable increased risk of death compared with patients with LG-NF and DI≥0.25 (adjusted hazard ratio, 2.41 [95% CI, 1.61-3.62]; <0.001), LG-NF and DI<0.25 (adjusted hazard ratio, 1.84 [95% CI, 1.24-2.73]; =0.003), and LG-LF and D≥0.25 (adjusted hazard ratio, 2.27 [95% CI, 1.42-3.63]; <0.001). In contrast, patients with LG-LF and DI≥0.25, LG-NF and DI<0.25, and LG-NF and DI≥0.25 had similar outcome. DI<0.25 showed incremental prognostic value in patients with LG-LF severe AS but not in patients with LG-NF severe AS. Conclusions Among patients with LG severe AS and preserved left ventricular ejection fraction, decreased DI<0.25 is a reliable parameter in patients with LF to identify a subgroup of patients at higher risk of death who may derive benefit from aortic valve replacement.



Circ Cardiovasc Imaging: 29 Sep 2020; 13:e010925
Altes A, Thellier N, Rusinaru D, Marsou W, ... Tribouilloy C, Maréchaux S
Circ Cardiovasc Imaging: 29 Sep 2020; 13:e010925 | PMID: 33076698
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Abstract

Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia.

Benschop L, Brouwers L, Zoet GA, Meun C, ... Roeters van Lennep JE,
Background
Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated.
Methods
We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies.
Results
Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia.
Conclusions
Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.



Circ Cardiovasc Imaging: 30 Oct 2020; 13:e010340
Benschop L, Brouwers L, Zoet GA, Meun C, ... Roeters van Lennep JE,
Circ Cardiovasc Imaging: 30 Oct 2020; 13:e010340 | PMID: 33190533
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