Bioimpedance Spectroscopy Reveals Important Association of Fluid Status and T1 -Mapping by Cardiovascular Magnetic Resonance.

BACKGROUND: Extracellular matrix expansion is a key pathophysiologic feature in heart failure and can be quantified noninvasively by cardiac magnetic resonance T1 -mapping. Free water within the interstitial space of the myocardium, however, may also alter T1 -mapping results. PURPOSE: To investigate the association between systemic fluid status and T1 -mapping by cardiac magnetic resonance. STUDY TYPE: Prospective, observational single-center study. POPULATION: Two-hundred eighty-five consecutive patients (44.4% female, 70.0 ± 14.9 years old) scheduled for cardiac MR due to various cardiac diseases. SEQUENCE AND FIELD STRENGTH: 1.5-T scanner (Avanto Fit, Siemens Healthineers, Erlangen, Germany). For T1 -mapping, electrocardiographically triggered modified-Look-Locker inversion (MOLLI) recovery sequence using a 5(3)3 prototype on a short-axis mid-cavity slice and with a four-chamber view was performed. ASSESSMENTS: MR parameters including native myocardial T1 -times using MOLLI and extracellular volume (MR-ECV) were assessed, and additionally, we performed bioimpedance analysis (BIA). Furthermore, demographic data and comorbidities were assessed. STATISTICS: Wilcoxon's rank-sum test, chi-square tests, and for correlation analysis, Pearson's correlation coefficients were used. Regression analyses were performed to investigate the association between patients' fluid status and T1 -mapping results. A P-value <0.05 was considered statistically significant. RESULTS: The mixed cohort presented with a mean overhydration (OH) of +0.2 ± 2.4 liters, as determined by BIA. By MR, native T1 -times were 1038 ± 51 msec and MR-ECV was 31 ± 9%. In the multivariable regression analysis, only OH was significantly associated with MR-ECV (adj. beta: 0.711; 95% CI: 0.28 to 1.14) along with male sex (adj. beta: 2.529; 95% CI: 0.51 to 4.55). In linear as well as multivariable analysis, only OH was significantly associated with native T1 times (adj. beta: 3.750; 95% CI: 1.27 to 6.23). CONCLUSION: T1 -times and MR-ECV were significantly associated with the degree of OH on BIA measurement. These effects were independent from age, sex, body mass index, and hematocrit. Patients' volume status may thus be an important factor when T1 -time and MR-ECV values are interpreted. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Feature Tracking of Global Longitudinal Strain by Using Cardiovascular MRI Improves Risk Stratification in Heart Failure with Preserved Ejection Fraction.

Background In heart failure with preserved ejection fraction (HFpEF), echocardiographic studies suggest that global longitudinal strain (GLS) has an impact on survival. Feature-tracking cardiovascular MRI also allows for strain analysis; however, to the knowledge of the authors, little is known about its prognostic value and whether it reflects severity of diffuse fibrosis, as assessed by cardiovascular MRI T1 mapping. Purpose To investigate the association between myocardial strain at cardiovascular MRI with extracellular volume by T1 mapping and outcome in participants with HFpEF. Materials and Methods In this secondary analysis of a prospective study (NCT03405987), consecutive participants with HFpEF underwent cardiovascular MRI between July 2012 and March 2018, including T1 mapping and three-dimensional strain analysis. Extracellular volume and strain results were assessed to determine if there was a correlation between these two factors. Cox regression was performed to determine the prognostic relevance of MRI-derived myocardial strain for a combined end point (events) of heart failure hospitalizations and cardiovascular death. Results In total, 206 consecutive participants with HFpEF (mean age, 71 years ± 8 [standard deviation]; 69% women) were included. Median myocardial global longitudinal strain (GLS) at MRI was -8.5% and showed low correlation with extracellular volume (r = 0.28; P = .003). A total of 109 events (53%) were recorded during a follow-up of 38 months ± 29. Participants with a GLS above the median had higher event rates (log-rank test, P < .001). By multivariable Cox regression analysis, GLS remained independently associated with outcome (hazard ratio, 1.06 per 1% strain increase; 95% confidence interval: 1.01, 1.11; P = .03) when corrected for risk factors including age, diabetes, renal function, N-terminal pro-b-type natriuretic peptide serum concentration, and right ventricular size and function. Conclusion In participants with heart failure with preserved ejection fraction, global longitudinal strain at cardiovascular MRI was correlated with extracellular volume by T1 mapping and was associated with cardiovascular events. © RSNA, 2020 Online supplemental material is available for this article.

Persistent atrial fibrillation in heart failure with preserved ejection fraction: Prognostic relevance and association with clinical, imaging and invasive haemodynamic parameters.

BACKGROUND: Atrial fibrillation (AF) is a frequent finding in HFpEF. However, its association with invasive haemodynamics, imaging parameters and outcome in HFpEF is not well established. Furthermore, the relevance of AF subtype with regard to outcome is unclear. This study sought to investigate the prognostic impact of paroxysmal and persistent AF in a well-defined heart failure with preserved ejection fraction (HFpEF) population. MATERIALS AND METHODS: Between 2010 and 2016, 254 HFpEF patients were prospectively enrolled. All patients underwent echocardiography as well as left and right heart catheterization. Patients without contraindications underwent CMR including T1 mapping. Follow-up and outcome data were collected. Patients with significant coronary artery disease were excluded. RESULTS: A total of 153 patients (60%) suffered from AF, 119 (47%) had persistent and 34 (13%) had paroxysmal AF. By multiple logistic regression analysis, persistent AF was independently associated with NT-proBNP (P = .003), NYHA functional class (P = .040), left and right atrial size (P = .022 and <.001, respectively), cardiac output (P = .002) and COPD (P = .034). After a median follow-up of 23 months (interquartile range 5-48), 92 patients (36%) reached the primary end point defined as hospitalization for heart failure or cardiovascular death. By multivariate Cox regression analysis, only persistent AF (P = .005) and six-minute walk distance (P = .011) were independently associated with the primary end point. CONCLUSIONS: Sixty percent of our HFpEF patients suffered from AF. Persistent but not paroxysmal AF was strongly associated with event-free survival and was independently related to NYHA functional class, serum NT-proBNP, atrial size, cardiac ouput and presence of COPD.

Three dimensional gait analysis in patients with symptomatic component mal-rotation after total knee arthroplasty.

PURPOSE: Purpose of the present cohort study was the determination of lower body function and rotation in patients with symptomatic component mal-rotation after total knee arthroplasty using instrumented 3D gait analysis. METHODS: A consecutive series of 12 patients (61.3 years ± 11.4 years) were included suffering under remaining pain or limited range of motion at least six months after total knee arthroplasty. A CT-scan according to the protocol of Berger et al. and instrumented 3D gait analysis were carried out including clinical examination, videotaping, and kinematic analysis using a Plug-in Gait model. Outcome variables were temporospatial parameters as well as kinematics in sagittal and transversal plane. Data for reference group were collected retrospectively and matched by age and gender. RESULTS: Temporospatial parameters of the study group showed decreased velocity, cadence, and step length as well as increased step time. Single limb support was reduced for the affected limb. In sagittal plane, maximum knee flexion during swing phase was reduced for the replaced knee joint. In transverse plane, there was hardly any difference between affected and non-affected limb. Compared to the reference group, both limbs show significant increased internal ankle rotation and external hip rotation. There were significant strong linear correlations between ankle rotation and hip rotation as well as ankle rotation and radiological tibial mal-rotation. CONCLUSIONS: Patients with symptomatic component mal-rotation after total knee arthroplasty showed typically functional deficits. The affected and non-affected limb showed significant increased internal ankle rotation and external hip rotation, while only the affected, replaced knee showed reduced internal knee rotation. Identification of rotational abnormalities of hip and ankle joints seems to be mandatory in TKA to identify the patient group with external hip rotation, internal ankle rotation, and an elevated risk for symptomatic rotational TKA component mal-alignment.

Diameter of the Pulmonary Artery in Relation to the Ascending Aorta: Association with Cardiovascular Outcome.

Purpose To investigate whether the pulmonary artery (PA)-to-ascending aorta (Ao) ratio is associated with outcome in unselected patients referred for cardiac magnetic resonance (MR) imaging. Materials and Methods This study prospectively enrolled 650 consecutive patients (47.2% women; mean age, 56.1 years ± 17.7 [standard deviation]). Diameters of PA and Ao were measured in axial black blood images. On the basis of previous results, a PA-to-Ao ratio of 1.0 or greater was chosen as the cutoff for further analysis. Univariable and multivariable Cox regression models were used to investigate the primary end point, which was defined as a composite of cardiovascular hospitalization and death. Results A PA-to-Ao ratio of 1.0 or greater was present in 131 (20.2%) patients. Patients with a PA-to-Ao ratio of 1.0 or greater were predominantly women (P = .010); more frequently presented with atrial fibrillation (P < .001), diabetes (P < .001), and impaired renal function (P < .001); and had higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < .001), larger left (P = .023) and right ventricles (RV; P = .002), and worse RV function (P < .001). Patients were followed for 17.8 months ± 12.9, during which 110 patients (16.9%) reached the primary end point. By Kaplan-Meier analysis, event-free survival was significantly worse in patients with a PA-to-Ao ratio of 1.0 or greater (log-rank test, P < .001). A PA-to-Ao ratio of 1.0 or greater was independently associated with outcome by multivariable Cox regression analysis, in addition to age, NT-proBNP serum levels, and RV size. Conclusion A PA-to-Ao ratio of 1.0 or greater identified patients at risk, most likely because of elevated PA pressures. On the basis of these results, the PA-to-Ao ratio should routinely be reported at cardiac MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Heart Failure with Preserved and Reduced Ejection Fraction in Hemodialysis Patients: Prevalence, Disease Prediction and Prognosis.

BACKGROUND/AIMS: Heart failure (HF) is a main cause of mortality of hemodialysis (HD) patients. While HF with reduced ejection fraction (HFrEF) is known to only affect a minority of patients, little is known about the prevalence, associations with clinical characteristics and prognosis of HF with preserved ejection fraction (HFpEF). METHODS: We included 105 maintenance HD patients from the Medical University of Vienna into this prospective single-center cohort study and determined the prevalence of HFpEF (per the 2013 criteria of the European Society of Cardiology) and HFrEF (EF <45%), using standardized post-HD transthoracic echocardiography. We also assessed clinical, laboratory and volume status parameters (by bioimpedance spectroscopy). These parameters served to calculate prediction models for both disease entities, while clinical outcomes (frequency of cardiovascular hospitalizations and/or cardiac death) were assessed prospectively over 27±4 months of follow-up. RESULTS: All but 4 patients (96%) had evidence of diastolic dysfunction. 70% of the entire cohort fulfilled HF criteria (81% HFpEF, 19% HFrEF). Age, female sex, body mass index, blood pressure and dialysis vintage were predictive of HFpEF (sensitivity 86%, specificity 63%; AUC 0.87), while age, female sex, NT pro-BNP, history of coronary artery disease and atrial fibrillation were predictive of HFrEF (sensitivity 85%, specificity 90%; AUC 0.95). Compared to patients without HF, those with HFpEF and HFrEF had a higher risk of hospitalization for cardiovascular reason and/or cardiac death (adjusted HR 4.31, 95% CI 0.46-40.03; adjusted HR 3.24, 95% CI 1.08-9.75, respectively). CONCLUSION: Diastolic dysfunction and HFpEF are highly prevalent in HD patients while HFrEF only affects a minority. Distinct patient-specific characteristics predict diagnosis of either entity with good accuracy.

The DEPFET Sensor-Amplifier Structure: A Method to Beat 1/f Noise and Reach Sub-Electron Noise in Pixel Detectors.

Depleted field effect transistors (DEPFET) are used to achieve very low noise signal charge readout with sub-electron measurement precision. This is accomplished by repeatedly reading an identical charge, thereby suppressing not only the white serial noise but also the usually constant 1/f noise. The repetitive non-destructive readout (RNDR) DEPFET is an ideal central element for an active pixel sensor (APS) pixel. The theory has been derived thoroughly and results have been verified on RNDR-DEPFET prototypes. A charge measurement precision of 0.18 electrons has been achieved. The device is well-suited for spectroscopic X-ray imaging and for optical photon counting in pixel sensors, even at high photon numbers in the same cell.

Forearm vasodilator reactivity in healthy male carriers of the 3q22.3 rs9818870 polymorphism.

BACKGROUND: A genome wide association study has identified a robust risk locus for cardiovascular disease on 3q22.3. However, the mechanisms by which the [C]/[T] polymorphism rs9818870 increases cardiovascular risk are unknown. This forearm blood flow (FBF) study addressed the question if the genetic association with cardiovascular disease in patients is preceded by incipient vasodilator impairment in young, healthy carriers of this new risk locus on chromosome 3. MATERIALS AND METHODS: After a pre-screening of 74 subjects 17 male healthy volunteers homozygous/heterozygous for a single nucleotide polymorphism (SNP) risk allele on 3q22.3 and a control group of 17 healthy volunteers not carrying the allele were included into this case-control study. RESULTS: Forearm vascular endothelium-dependent and -independent vasodilator responses were in the normal range in both groups, although endothelium-dependent FBF reactivity to acetylcholine was significantly higher in SNP carriers of the risk allele. CONCLUSION: The augmented endothelium-dependent vasodilation of the forearm resistance vasculature does not support the presence of endothelial dysfunction in young SNP carriers and indicates that other mechanisms are responsible for the strong association between coronary artery diseases and the rs9818870 polymorphism, located on 3q22.3.

Pulmonary artery to aorta ratio for the detection of pulmonary hypertension: cardiovascular magnetic resonance and invasive hemodynamics in heart failure with preserved ejection fraction.

BACKGROUND: Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF. METHODS AND RESULTS: 159 consecutive HFpEF patients were prospectively enrolled. Of these, 111 underwent CMR and invasive hemodynamic evaluation. By invasive assessment 64 % of patients suffered from moderate/severe PH (mean pulmonary artery pressure (mPAP) ≥30 mmHg). Significant differences between groups with and without moderate/severe PH were observed with respect to PA diameter (30.9 ± 5.1 mm versus 26 ± 5.1 mm, p < 0.001), PA:Ao ratio (0.93 ± 0.16 versus 0.78 ± 0.14, p < 0.001), and SMT diameter (4.6 ± 1.5 mm versus 3.8 ± 1.2 mm; p = 0.008). The strongest correlation with mPAP was found for PA:Ao ratio (r = 0.421, p < 0.001). By ROC analysis the best cut-off for the detection of moderate/severe PH was found for a PA:Ao ratio of 0.83. Patients were followed for 22.0 ± 14.9 months. By Kaplan Meier analysis event-free survival was significantly worse in patients with a PA:Ao ratio ≥0.83 (log rank, p = 0.004). By multivariable Cox-regression analysis PA:Ao ratio was independently associated with event-free survival (p = 0.003). CONCLUSION: PA:Ao ratio is an easily measureable noninvasive indicator for the presence and severity of PH in HFpEF, and it is related with outcome.

Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans.

INTRODUCTION: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects. MATERIAL AND METHODS: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously. RESULTS: Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2. CONCLUSION: Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.

A 64k pixel CMOS-DEPFET module for the soft X-rays DSSC imager operating at MHz-frame rates.

The 64k pixel DEPFET module is the key sensitive component of the DEPFET Sensor with Signal Compression (DSSC), a large area 2D hybrid detector for capturing and measuring soft X-rays at the European XFEL. The final 1-megapixel camera has to detect photons with energies between [Formula: see text] and [Formula: see text], and must provide a peak frame rate of [Formula: see text] to cope with the unique bunch structure of the European XFEL. This work summarizes the functionalities and properties of the first modules assembled with full-format CMOS-DEPFET arrays, featuring [Formula: see text] hexagonally-shaped pixels with a side length of 136 µm. The pixel sensors utilize the DEPFET technology to realize an extremely low input capacitance for excellent energy resolution and, at the same time, an intrinsic capability of signal compression without any gain switching. Each pixel of the readout ASIC includes a DEPFET-bias current cancellation circuitry, a trapezoidal-shaping filter, a 9-bit ADC and a 800-word long digital memory. The trimming, calibration and final characterization were performed in a laboratory test-bench at DESY. All detector features are assessed at [Formula: see text]. An outstanding equivalent noise charge of [Formula: see text]e-rms is achieved at 1.1-MHz frame rate and gain of 26.8 Analog-to-Digital Unit per keV ([Formula: see text]). At [Formula: see text] and [Formula: see text], a noise of [Formula: see text] e-rms and a dynamic range of [Formula: see text] are obtained. The highest dynamic range of [Formula: see text] is reached at [Formula: see text] and [Formula: see text]. These values can fulfill the specification of the DSSC project.

Cardiac remodeling in ambitious endurance-trained amateur athletes older than 50 years-an observational study.

BACKGROUND: Data on cardiac remodeling in veteran athletes are conflicting but of clinical importance. METHODS: Sixty-nine clinically stable and healthy individuals >50 years were identified (median 55 (IQR 52-64), 26% female). Echocardiographic features were identified in individuals, who have performed endurance sports at 70% of their maximum heart rate for at least 1 hour 3 times/ week over the previous 5 years. RESULTS: Median training time in all participants was 6 hours per week. Therefore, based on these 6 hours of weekly training, participants were grouped into 45 ambitious endurance-trained amateur athletes (EAA) and 24 recreationally active endurance-trained athletes (RAP) training ≥6 hours (6-10) and <6 hours (3.5-5), respectively. Left ventricular (LV) diameters were slightly larger in EAA than in RAP (27 mm/m2 (25-28) vs. 25 mm/m2 (24-27), p = 0.023) and EAA showed preserved diastolic function (p = 0.028) with lower E/E' ratio (7 (6-9) vs. 9 (7-10), p = 0.039). Interventricular septal thickness and relative wall thickness ratio were similar. Global right ventricular and LV strain were similar, but left atrial (LA) reservoir strain was higher in EAA than in RAP (27% (22-34) vs. 20% (15-29), p = 0.002). CONCLUSIONS: Endurance training in healthy athletes >50 years is not associated with chamber dilatation or LV hypertrophy. A weekly training duration of ≥6 hours seems beneficial to preserve diastolic function associated with an increased LA reservoir function.

Prognostic impact of left atrial function in heart failure with preserved ejection fraction in sinus rhythm vs. persistent atrial fibrillation.

AIMS: We sought to determine the prognostic impact of left atrial (LA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF). METHODS AND RESULTS: We enrolled consecutive HFpEF patients and assessed indexed LA volumes and emptying fractions (LA-EF) on cardiac magnetic resonance imaging. In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N-terminal prohormone of brain natriuretic peptide evaluation. We prospectively followed patients and used Cox regression models to determine the association of LA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70 ± 8 years old) were included of whom 92 (49%) were in persistent AF. Sixty-five patients reached the combined endpoint during a follow-up of 31 (9-57) months. Multivariate Cox regression adjusted for established risk factors revealed that LA-EF was significantly associated with outcome in patients in SR [adjusted hazard ratio 2.14; 95% confidence interval (1.32-3.47) per 1-SD decline, P = 0.002]. In persistent AF, no LA imaging parameter was related to outcome. By receiver operating characteristic and restricted cubic spline analyses, we identified an LA-EF ≥ 40% as best indicator for favourable outcomes in patients with HFpEF and SR. Persistent AF carried a similar risk for adverse outcome compared with impaired LA-EF (<40%) in SR (log-rank, P = 0.340). CONCLUSIONS: In HFpEF patients in SR, impaired LA-EF is independently associated with worse cardiovascular outcome, which is similar to persistent AF. In persistent AF, LA parameters lose their prognostic ability.

Transcatheter Versus Surgical Valve Repair in Patients with Severe Mitral Regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TMVR) is increasingly performed. However, its efficacy in comparison with surgical MV treatment (SMV) is unknown. METHODS: Consecutive patients with severe mitral regurgitation (MR) undergoing TMVR (68% functional, 32% degenerative) or SMV (9% functional, 91% degenerative) were enrolled. To account for differences in baseline characteristics, propensity score matching was performed, including age, EuroSCORE-II, left ventricular ejection fraction, and NT-proBNP. A composite of heart failure (HF) hospitalization/death served as primary endpoint. Kaplan-Meier curves and Cox-regression analyses were used to investigate associations between baseline, imaging, and procedural parameters and outcome. RESULTS: Between July 2017 and April 2020, 245 patients were enrolled, of whom 102 patients could be adequately matched (73 y/o, 61% females, EuroSCORE-II: 5.7%, p > 0.05 for all). Despite matching, TMVR patients had more co-morbidities at baseline (higher rates of prior myocardial infarction, coronary revascularization, pacemakers/defibrillators, and diabetes mellitus, p < 0.009 for all). Patients were followed for 28.3 ± 27.2 months, during which 27 events (17 deaths, 10 HF hospitalizations) occurred. Postprocedural MR reduction (MR grade <2: TMVR vs. SMV: 88% vs. 94%, p = 0.487) and freedom from HF hospitalization/death (log-rank: p = 0.811) were similar at 2 years. On multivariable Cox analysis, EuroSCORE-II (adj.HR 1.07 [95%CI: 1.00-1.13], p = 0.027) and residual MR (adj.HR 1.85 [95%CI: 1.17-2.92], p = 0.009) remained significantly associated with outcome. CONCLUSIONS: In this propensity-matched, all-comers cohort, two-year outcomes after TMVR versus SMV were similar. Given the reported favorable long-term durability of TMVR, the interventional approach emerges as a valuable alternative for a substantial number of patients with functional and degenerative MR.

Endurance Training Improves Oxygen Uptake and Endurance Capacity in Patients With Moderate to Severe Valvular Disease.

Aim: Peak oxygen uptake (peakVO2) is one of the strongest predictors of survival in patients with valvular heart disease. The purpose of this study was to determine whether endurance training improves peakVO2 and endurance capacity in patients with moderate-severe aortic and mitral valve disease. Methods: 30 patients with moderate-severe valvular heart disease were randomly assigned to 12 weeks of endurance training (TG) (n = 16) or standard care (SC) (n = 14). PeakVO2 and maximum working capacity (Wattmax) were assessed by cardiopulmonary exercise testing, as well as submaximal endurance test at 80% of peakVO2 at baseline and after 12 weeks. Results: There was a significant improvement in peakVO2 from 27.2 ± 5.9 ml/kg to 30.4 ± 6.3 ml/kg (P < 0.001) in TG compared to the SC (peakVO2 from 24.6 ± 4.4 to 24.7 ± 3.8) and in the Wattmax from 151.8 ± 41.0 Watt to 171.2 ± 49.7 Watt in the TG compared to the SC (152.9 ± 35.6 Watt to 149.2 ± 28.4 Watt). The endurance capacity increased significantly from 17.0 ± 9.4 min to 32.8 ± 16.8 min (p = 0.003) in the TG compared to the SC (11.7 ± 6.2 min to 11.2 ± 7.6 min). The heart rate during the endurance test decreased in the TG from 154 ± 14 b/min to 142 ± 20 b/min for the same workload. No changes could be seen in the SC. Conclusion: Endurance training in patients with moderate to severe valvular heart disease increased significantly the peakVO2 as well as the endurance capacity.

Identification of Subclinical Microvascular Biomarkers in Coronary Heart Disease in Retinal Imaging.

Purpose: Cardiovascular disease and foremost coronary heart disease (CHD) are the worldwide leading causes of death. The aim of this study was to use non-invasive, multimodel retinal imaging to define microvascular features in patients with and without coronary angiography (CA)-confirmed CHD. Methods: In this prospective, cross-sectional pilot study we included adult patients who presented to a tertiary referral center for elective CA due to suspected CHD. All patients underwent widefield fundus photography for retinopathy grading. Optical coherence tomography angiography was used to measure vessel density (VD) of the individual capillary plexuses in 6 × 6-mm macular volume scans. Adaptive optics imaging was performed to assess the first-order arteriolar lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and wall cross-section area, as well as to qualitatively describe vessel morphology. Results: Of the included 45 patients (13 females; 65 ± 10 years old), 27 were confirmed with CHD in elective CA. The most prevalent retinal vascular pathologies were arteriovenous nickings, focal arterial narrowings, and microaneurysms. VD in the superficial capillary plexus, deep capillary plexus, and choriocapillaris was lower in CHD patients, although the odds ratios were not significantly different from 1 (P = 0.06-0.92). Median arterial LD, TD, and WLR values were 98.3 µm (interquartile range [IQR] = 13.0), 122.9 µm (IQR = 17.6), and 0.26 µm (IQR = 0.07), respectively, with a trend toward a higher WLR in CHD patients. Conclusions: In a cardiovascular risk population, high-resolution quantitative and qualitative microvascular phenotyping in the retina may provide valuable subclinical indicators for coronary artery impairment, although larger clinical trials are needed. Translational Relevance: Subclinical retinal microvascular changes may serve as non-invasive, cost-effective biomarkers for risk stratification of patients with CHD.

Right ventricular function and outcome in patients undergoing transcatheter aortic valve replacement.

AIMS: Right ventricular dysfunction (RVD) on echocardiography has been shown to predict outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). However, a comparison with the gold standard, RV ejection fraction (EF) on cardiovascular magnetic resonance (CMR), has never been performed. METHODS AND RESULTS: Consecutive patients scheduled for TAVR underwent echocardiography and CMR. RV fractional area change (FAC), tricuspid annular plane systolic excursion, RV free-lateral-wall tissue Doppler (S'), and strain were assessed on echocardiography, and RVEF on CMR. Patients were prospectively followed. Adjusted regression analyses were used to report the strength of association per 1-SD decline for each RV function parameter with (i) N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, (ii) prolonged in-hospital stay (>14 days), and (iii) a composite of heart failure hospitalization and death. Two hundred and four patients (80.9 ± 6.6 y/o; 51% female; EuroSCORE-II: 6.3 ± 5.1%) were included. At a cross-sectional level, all RV function parameters were associated with NT-proBNP levels, but only FAC and RVEF were significantly associated with a prolonged in-hospital stay [adjusted odds ratio 1.86, 95% confidence interval (CI) 1.07-3.21; P = 0.027 and 2.29, 95% CI 1.43-3.67; P = 0.001, respectively]. A total of 56 events occurred during follow-up (mean 13.7 ± 9.5 months). After adjustment for the EuroSCORE-II, only RVEF was significantly associated with the composite endpoint (adjusted hazard ratio 1.70, 95% CI 1.32-2.20; P < 0.001). CONCLUSION: RVD as defined by echocardiography is associated with an advanced disease state but fails to predict outcomes after adjustment for pre-existing clinical risk factors in TAVR patients. In contrast, RVEF on CMR is independently associated with heart failure hospitalization and death.

Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism.

AIM: Recently, a novel susceptibility locus for coronary artery disease (CAD) has been identified on chromosome 9p21.3, linked to the single-nucleotide polymorphism (SNP) rs1333049 G>C. However, the physiological mechanism through which this locus confers an increased CAD-risk is still unknown. The aim of the present case-control study was to test whether this chromosome 9p21.3 locus, represented by the rs1333049 variant, is associated with altered vasodilator resistance vessel function in healthy young volunteers. DESIGN AND RESULTS: A total of 97 healthy male volunteers were screened for homozygous carriers of either the G- or the C-allele, the minor allele in European populations. Forearm blood flow (FBF) reactivity to acetylcholine (ACh) and glycerol trinitrate (GTN) was then studied in 10 C/C-genotype carriers compared with 10 control subjects harbouring the G/G-genotype. FBF responses to ACh and GTN were reduced in subjects homozygous for the C-allele of the rs1333049 SNP (P < 0.05). FBF reactivity to the highest dose of ACh and GTN was 95% and 74% lower when compared with control subjects with the G/G-genotype. CONCLUSION: Our study revealed a functional impairment in forearm artery vasodilator resistance in carriers of the rs1333049 C/C-genotype, thus providing evidence for a first physiological functional link underlying the genetic association of the 9p21.3 locus with an increased cardiovascular risk.

Sex Differences in Left Ventricular Remodeling and Outcomes in Chronic Aortic Regurgitation.

BACKGROUND: Left ventricular (LV) dilatation is a key compensatory feature in patients with chronic aortic regurgitation (AR). However, sex-differences in LV remodeling and outcomes in chronic AR have been poorly investigated so far. METHODS: We performed cardiovascular magnetic resonance imaging (CMR) including phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RegF) at the sinotubular junction, in consecutive patients with at least mild AR on echocardiography. We assessed LV size (end-diastolic volume indexed to body surface area, LVEDV/BSA) and investigated sex differences between LV remodeling and increasing degrees of AR severity. Cox-regression models were used to test differences in outcomes between men and women using a composite of heart failure hospitalization, unscheduled AR intervention, and cardiovascular death. RESULTS: 270 consecutive patients (59.6% male, 59.8 ± 20.8 y/o, 59.6% with at least moderate AR on echocardiography) were included. On CMR, mean RegF was 18.1 ± 17.9% and a total of 65 (24.1%) had a RegF ≥ 30%. LVEDV/BSA was markedly closer related with AR severity (RegF) in men compared to women. Each 1-SD increase in LVEDV/BSA (mL/m2) was associated with a 9.7% increase in RegF in men and 5.9% in women, respectively (p-value for sex-interaction < 0.001). Based on previously published reference values, women-in contrast to men-frequently had a normal LV size despite severe AR (e.g., for LVEDV/BSA on CMR: 35.3% versus 8.7%, p < 0.001). In a Cox-regression model adjusted for age, LVEDV/BSA and RegF, women were at significantly higher risk for the composite endpoint when compared to men (adj. HR 1.81 (95%CI 1.09-3.03), p = 0.022). CONCLUSION: In patients with chronic AR, LV remodeling is a hallmark feature in men but not in women. Severity of AR may be underdiagnosed in female patients in the absence of LV dilatation. Future studies need to address the dismal prognosis in female patients with chronic AR.

Left Main Coronary Artery Disease and Outcomes after Percutaneous Coronary Intervention for Chronic Total Occlusions.

BACKGROUND: Concomitant left main coronary artery (LMCA) disease in patients with chronic total occlusions (CTO) commonly results in referral for coronary artery bypass grafting, although the impact of LMCA in CTO patients remains largely unknown. Nevertheless, patient selection for percutaneous coronary intervention of CTOs (CTO-PCI) or alternative revascularization strategies should be based on precise evaluation of the coronary anatomy to anticipate those patients that most likely benefit from a procedure and not on strict adherence to perpetual clinical practice. Therefore, the aim of this study was to assess the impact of LMCA disease on long-term outcomes in patients undergoing percutaneous coronary intervention for CTO. METHODS: We enrolled 3860 consecutive patients undergoing PCI for at least one CTO lesion and investigated the predictive value of concomitant LMCA disease. All-cause mortality was defined as the primary study endpoint. RESULTS: We observed that LMCA disease is significantly associated with mortality. In the Cox regression analysis, we observed a crude hazard ratio (HR) 1.59 (95% confidence interval (CI) 1.23-2.04, p < 0.001) for patients with LMCA disease as compared to patients without. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. CONCLUSION: LMCA disease is associated with excess mortality in CTO patients. Specifically, anatomical features such as CTO of the circumflex artery represent a high risk patient population.