Impact of closed loop stimulation on prognostic cardiopulmonary variables in patients with chronic heart failure and severe chronotropic incompetence: a pilot, randomized, crossover study.

AIMS: Clinical effects of rate-adaptive pacing in heart failure patients with chronotropic incompetence (CI) undergoing cardiac resynchronization therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS in CRT patients with severe CI, focusing primarily on key prognostic variables assessed by cardiopulmonary exercise (CPX) testing. METHODS AND RESULTS: In the randomized, crossover, multicentre BIO|CREATE study, 20 CRT patients with severe CI and NYHA Class II/III (60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode, or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode). Patients underwent symptom-limited treadmill-based CPX test in each mode. An improvement (decrease) of the ventilatory efficiency (VE) slope of ≥5% during CLS was regarded as positive response to CLS. Seventeen patients with full data sets had a mean intra-individual VE slope change of -1.8 ± 3.0 (-4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS responders, with a -6.1 ± 2.7 (-16.4%) slope change (P = 0.029). Compared to non-responders, CLS responders had a higher left ventricular (LV) ejection fraction (46 ± 3 vs. 36 ± 9%; P = 0.0070), smaller end-diastolic LV volume (121 ± 34 vs. 181 ± 41 mL; P = 0.0085), smaller end-systolic LV volume (65 ± 23 vs. 114 ± 39 mL; P = 0.0076), and were predominantly in NYHA Class II (P = 0.0498). CONCLUSION: The data of the present pilot study are compatible with the notion that CLS activation may improve VE slope in CRT patients with severe CI and less advanced heart failure. Further research is needed to determine the long-term clinical outcomes of CLS.

Instructing Ultrasound-guided Examination Techniques Using a Social Media Smartphone App.

Social media applications on smartphones allow for new avenues of instruction in sports medicine and exercise sciences. This study tested the feasibility of instructing health care personnel through videos of ultrasound vascular measurements distributed by a social media messenger application. After two training sessions with an ultrasound device, voluntary physicians (n=10) and nurses (n=10) received a video for the performance of an ultrasound-guided determination of intima-media-thickness and diameter of the femoral arteries via a social media messenger application. All participants examined the same healthy human subject. There was no significant difference between the groups regarding overall time of performance, measurements of the femoral arteries, or a specifically designed "assessment of mobile imparted arterial ultrasound determination" score. The physicians group achieved significantly higher scores in the established "objective structured assessment of ultrasound skills" score (p=0.019). Approval of the setting was high in both groups. Transmission of videos via social media applications can be used for instructions on the performance of ultrasound-guided vascular examinations in sports medicine, even if investigators' performances differ depending on their grade of ultrasound experience. In the future, the chosen approach should be tested in practical scientific examination settings.

Closed loop stimulation in patients with chronic heart failure and severe chronotropic incompetence: Responders versus non-responders.

BACKGROUND: Clinical effects of rate-adaptive pacing (RAP) are unpredictable and highly variable among cardiac resynchronization therapy (CRT) patients with chronotropic incompetence. Physiologic sensors such as Closed Loop Stimulation (CLS), measuring intracardiac impedance changes (surrogate for ventricular contractility), may add clinical benefit and help identify predictors of response to RAP. The objective of the present BIOlCREATE study subanalysis was to identify criteria for selection of CRT patients who are likely to respond positively to CLS-based RAP. METHODS: In the randomized, crossover BIO|CREATE study, CRT patients with severe chronotropic incompetence and NYHA class II/III were randomized to CLS with conventional upper sensor rate programming or to no RAP for 1 month, followed by crossover for another month. At 1-month and 2-month follow-ups, patients underwent treadmill-based cardiopulmonary exercise test. Positive CLS response was defined as a ≥ 5% reduction in ventilatory efficiency slope. Eight of 17 patients (47%) were CLS responders. In this subanalysis, we compared responders and non-responders to explore outcomes, mechanisms, and predictors. RESULTS: All cardiopulmonary variables, health-related quality of life, patient activity status, and NT-proBNP concentration showed favorable trend in CLS responders and unfavorable trend in non-responders, underlining the need to find predictors. Following all analyses, we recommend CLS in heart failure patients with improved left ventricular ejection fraction (LVEF >40%, after a ≥ 10-point increase from a CRT-pre-implant value of ≤40%), corresponding to 'HFimpEF' in the universal classification system. CONCLUSION: HFimpEF patients are likely to benefit from CLS-based RAP, in contrast to 'HFrEF' (heart failure with reduced LVEF [≤40%]).

Visualization of chronic myocardial infarction using the intravascular contrast agent MS-325 (gadofosveset) in patients.

AIMS: The aim of this study was to evaluate the potential of visualizing chronic myocardial infarction in patients using the intravascular CA MS-325 (gadofosveset, EPIX Pharmaceuticals, Mass, USA). METHODS: Nine patients were enrolled in a clinical phase II multicenter trial for MRCA and perfusion imaging using MS-325. They had objective evidence of chronic myocardial infarction as visualized by previously performed late gadolinium (Gd) enhancement imaging (LGE) with a conventional extracellular Gd-DTPA CA (Magnevist, Bayer Healthcare, Germany, 0.2 mmol/kg/body weight) serving as reference standard. A prepulse-optimized LGE study was performed immediately and at several time points after injection of MS-325 (0.05 mmol/kg/body weight). The number and localization of segments demonstrating LGE with MS-325 as well as signal intensities were compared with the reference standard (Gd-DTPA). RESULTS: Using MS-325, LGE could be detected at every time point in all 9 patients. The accuracy of LGE with MS-325 as compared to LGE with Gd-DTPA was highest 54 ± 4 minutes after contrast injection, resulting in a sensitivity of 84% with a specificity of 98%. CONCLUSION: The intravascular CA MS-325 has the potential to visualize chronic myocardial infarction. However, in comparison with Gd-DTPA, the transmural extent and the number of segments are smaller.

Salivary Diagnostic for Monitoring Strenuous Exercise-A Pilot Study in a Cohort of Male Ultramarathon Runners.

Intense physical stress, such as that in ultramarathon running, affects the immune system. For monitoring in sports medicine, non-invasive methods, e.g., salivary analysis, are of interest. This pilot cohort study aimed to assess changes in salivary parameters in response to an ultramarathon. The results were compared to blood parameters. Male, healthy finishers (n = 9, mean age: 48 ± 8.8 years, mean height: 1.8 ± 0.1 m, mean weight: 72.5 ± 7.2 kg, mean BMI: 23.5 ± 1.9 kg/cm²) of a 160 km ultramarathon were included. Saliva and blood samples were collected at three time points: T1 (baseline), T2 (shortly after the ultramarathon) and T3 (after recovery). In saliva, cortisol, testosterone, IL-1ß, IL-6, IL-8, IL-10, TNF-α, albumin, IgA, α-amylase, aMMP-8, and neopterin were assessed via ELISA. In blood, cortisol, testosterone, IL-1ß, IL-6, IL-8, IL-10, TNF-α, blood cell counts, procalcitonin, CRP, osmolality, albumin, and α-amylase were analyzed. The statistical evaluation comprised longitudinal testing and cross-sectional testing between saliva and blood using ratios of T2 and T3 to baseline values. Various parameters in saliva and blood changed in response to the ultramarathon. Comparing blood and saliva, the longitudinal changes of testosterone (p = 0.02) and α-amylase (p = 0.03) differed significantly. Despite the limitations of the study, it underlines that saliva is an interesting option for comprehensive monitoring in sports medicine and necessitates further studies.

Influence of a 100-mile ultramarathon on heart rate and heart rate variability.

AIMS: This study aimed to investigate the impact of an ultramarathon (UM) with a distance of 100 miles on heart rate (HR) and heart rate variability (HRV). METHODS: 28 runners (25 men and 3 women) underwent 24-hour Holter ECG monitoring 1 week before the UM, immediately after the UM and after a week of recovery. The influence of age, body mass index (BMI), HR and HRV on the run time and recovery was investigated. RESULTS: A rise in the baseline HR (18.98%) immediately after the run accompanied by a significant drop in the SD of all normal RR intervals (7.12%) 1 week after. Except for the runners' age, BMI, HR and HRV showed no influence on the competition time. Full return of HRV to the athletes' baseline did not occur within 1 week. There were no significant differences between finishers and non-finishers in the analysed parameters. CONCLUSION: The present results show that a 100-mile run leads to an increase in sympathetic activity and thus to an increase in HR and a decrease in HRV. Also, HRV might be a suitable parameter to evaluate the state of recovery after a 100-mile run but does not help to quantify the status of recovery, as the damage to the tendomuscular system primarily characterises this after completing a UM.

Home-Based Long-Term Physical Endurance and Inspiratory Muscle Training for Children and Adults With Fontan Circulation-Initial Results From a Prospective Study.

BACKGROUND: Patients with congenital heart disease (CHD)-including those after Fontan operation-are encouraged to be physically active. AIM: To prospectively determine the effects of an individually adapted, home-based cycle ergometer endurance training in combination with inspiratory muscle training (IMT) in pediatric and adult Fontan patients. We, herein, report the results of the initial 10-months follow-up (phase 1). METHODS: 18 patients (median age 16.5 years; range 10-43 years) completed baseline check-ups, and 4 and 10 months follow-up visits, which each included cardiopulmonary exercise testing (CPET), bodyplethysmography (including measurement of respiratory muscle strength), and a quality of life questionnaire (PedsQL™). The training program consisted of a home-based cycle ergometer endurance training on a "Magbike® AM-5i/3i" (DKN Technology®, Clermont-Ferrand, France) and IMT with a handheld "POWERbreathe® Medic plus" device. Patients performed 90 min of endurance training per week in addition to IMT (30 breaths per day, 6-7 times per week). After the first 4 months, patients underwent additional interval training. RESULTS: After 10 months of training, we observed significant increases in maximum relative workload (W/kg, p = 0.003) and in maximum inspiratory (MIP, p = 0.002) and expiratory (MEP, p = 0.008) pressures. Peak VO2 values did not increase significantly as compared to baseline (p = 0.12) in the entire cohort (n = 18), but reached statistical significance in a subgroup analysis of teenage/adult patients (n = 14; p = 0.03). Patients' subjective quality of life did not show any significant changes after 10 months of training. DISCUSSION: In Fontan patients, an individually adapted home-based training is safe and associated with improvements in some CPET variables. However, these improvements did not translate into an improved QoL after 10 months. With an unclear, but most likely negative, impact of the COVID-19 pandemic, improvements in QoL may become evident during further follow-up (phase 2 of the study).

Visualization of the cardiac venous system using cardiac magnetic resonance.

We sought to investigate the value of cardiac magnetic resonance to depict cardiac venous anatomy. For cardiac resynchronization therapy the lead for the left ventricle is usually placed by transvenous approach into a tributary of the coronary sinus (CS). Knowledge of the anatomy and variations of the cardiac venous system may facilitate the positioning of the left ventricle lead. The cardiac magnetic resonance examinations of 23 subjects (16 volunteers and 7 patients) were retrospectively analyzed. All examinations were performed using navigator-gated whole-heart steady-state free precession coronary artery imaging after administration of intravascular contrast agents (gadofosveset in volunteers; Gadomer-17 in patients). The cardiac venous system was visualized in all subjects. The most frequent anatomical variant observed (in 12 subjects [52%]) was a connection of the small cardiac vein to the CS at the crux cordis. In 10 subjects (44%) the small veins entered the right atrium independently from the CS, and the posterior interventricular vein was connected to the CS at the crux cordis. Only one subject had a disconnection between the CS and posterior interventricular vein, which entered into the right atrium independently. The mean distance of the posterior vein of the left ventricle and the left marginal vein to the ostium of the CS was 15.2+/-4.7 mm and 49.7+/-14.1 mm, respectively. In conclusion, the anatomy of the cardiac venous system and its anatomical variability can be described using cardiac magnetic resonance. Its preimplantation visualization may help to facilitate the implant procedure and to reduce fluoroscopy time.

Noninvasive determination of coronary blood flow velocity with cardiovascular magnetic resonance in patients after stent deployment.

BACKGROUND: In patients with coronary artery stents, no direct noninvasive coronary artery imaging is possible with magnetic resonance (MR). A well-established method for the assessment of the functional significance of a coronary lesion is the measurement of coronary flow reserve by invasive intracoronary Doppler. The purpose of the study was to determine coronary flow velocity reserve (CFVR) with MR after stent deployment. METHODS AND RESULTS: Thirty-eight patients after successful PTCA and stent deployment were included. CFVR was measured perpendicular to the artery distal to the stent using phase-contrast velocity quantification at rest and during adenosine-stimulated hyperemia with a 1.5T MR tomograph (ACS NT, Philips). Measurements were repeated after 3 months and compared with invasive coronary angiography. In 18 patients, additional invasive Doppler flow measurements were obtained. CFVR could be determined in 29 of 38 (76%) of the patients. After 3 months, significant differences were obtained between coronary arteries with and without restenosis. Using a threshold of 1.2, a sensitivity of 83% with a specificity of 94% was achieved for > or =75% stenoses. CFVR with CMR was similar to Doppler results (r=0.87), with a mean relative difference of 7.5%. CONCLUSIONS: In patients with preserved coronary microcirculating vasoreactivity that are suitable for MR coronary angiography and flow assessments, CMR measures of coronary blood flow velocities reserve may be used to detect in-stent restenosis.

Cardiac involvement of Echinococcus granulosus evaluated by multi-contrast CMR imaging.

Cardiac manifestations of hydatid cysts are rare and occur in about 0.2 to 3% of all cases of human hydatidosis. We report the case of a young man with a known 4-year old infection with Echinoccus granulosus. Cardiovascular magnetic resonance imaging (CMR) was performed and showed two cysts in the left ventricular wall. The smaller cyst had a thin, noncontinuous membrane to the left ventricle. The T1- and T2-weighted images showed an isointense signal of the cysts compared to blood; fat-suppressed images showed no fatty components. To highlight the potential small signal differences we assigned the contents of the gray images to red, green and blue channels of a conventional color image. Blood and the content of the cysts had the same color, making a connection between the cysts and the LV blood pool highly probable. This was confirmed by first pass perfusion imaging, which showed simultaneous contrast agent arrival in the left ventricular cavity and the cysts. Delayed enhancement (DE) revealed fibrotic tissue surrounding the cysts. MR seems to be the most complete method of diagnosing the disease, as anatomical structures, type of content of the cyst (liquid or solid) and its relation to the myocardium can be assessed within one study.

Strain-encoded MRI to evaluate normal left ventricular function and timing of contraction at 3.0 Tesla.

PURPOSE: To define the reproducibility of strain-encoded (SENC) magnetic resonance imaging (MRI) for assessment of regional left ventricular myocardial strain and timing of contraction in a 3T MRI system. MATERIALS AND METHODS: The study population consisted of 16 healthy subjects. SENC measurements were performed in three short-axis (SA) slices (apical, mid, and basal) and three long-axis (LA) views (two-, three-, and four-chamber) for assessment of maximal transmural systolic strain and time to peak strain. To assess the interobserver and interstudy reproducibility, analysis of SENC MRI was performed by two independent observers who were blinded to each other's results and four studies were repeated on a different day. RESULTS: Maximal longitudinal strain was highest at the apex, as was maximal circumferential strain. Peak longitudinal strain occurred earliest at the base, as did peak circumferential strain. Interclass correlation coefficient between observers and repeated studies ranged from 0.92 to 0.98 (P < 0.001 for all). CONCLUSION: The present study demonstrates the ability of SENC MRI to define regional left ventricular strain and the time sequence of regional strain. SENC MRI may represent a highly objective method for quantifying regional left ventricular function.

Regional right ventricular function and timing of contraction in healthy volunteers evaluated by strain-encoded MRI.

PURPOSE: To prospectively determine the feasibility and accuracy of strain-encoded (SENC) magnetic resonance imaging (MRI) for the characterization of the right ventricular free wall (RVFW) strain and timing of contraction at 3.0 Tesla (3T) MRI. MATERIALS AND METHODS: In 12 healthy volunteers the RVFW was divided into three segments (anterior, lateral, and inferior) in each of three short-axis (SA) slices (apical, mid, and basal) and into three segments (apical, mid, and basal) in a four-chamber view. The study was repeated on a different day and interobserver and interstudy agreements were evaluated. RESULTS: Maximal systolic longitudinal strain values were highest at the apex and base, with a pronounced decrease in the medial segments (apex: -19.1% +/- 1.4; mid: -17.4% +/- 2; base: -19.4% +/- 2.4, P < 0.001), and maximal systolic circumferential strain showed the highest values at the apex (apex: -18.1% +/- 1.7; mid: -17.6% +/- 1.2; base: -16.6% +/- 0.9, P < 0.001). Peak systolic longitudinal and circumferential shortening occurred earliest at the apex compared to the mid-ventricle and base. Excellent interobserver and interstudy correlation and agreement were observed. CONCLUSION: The use of SENC MRI for the assessment of normal RV contraction pattern is feasible and accurate in 3T MRI.

Whole-heart coronary magnetic resonance angiography with MS-325 (Gadofosveset).

BACKGROUND: Magnetic resonance coronary angiography (MRCA) is limited by a low signal-to-noise-ratio (SNR), low spatial resolution, and limited coverage of the coronary artery tree. These aspects might be significantly improved by intravascular contrast agents. The aim of the study was to evaluate the feasibility of whole-heart contrast-enhanced MRCA using the intravascular contrast agent gadofosveset, formerly known as MS-325. MATERIAL/METHODS: Free-breathing navigator-gated MRCA using a single 3D volume with transversal slice orientation before and after injection of MS-325 (0.05 mmol/kg body-weight) was performed in 17 volunteers (6 men, aged 30+/-8 years). Signal intensities from the myocardium and left ventricular blood were assessed for non-enhanced and contrast-enhanced images. Signal-to-noise ratio of blood and contrast-to-noise ratios (CNR) were calculated. Image quality (0: no visualization, 1: nondiagnostic, 2: moderate, 3: good, 4: excellent) and MR angiograms (15-segment model following AHA/ACC guidelines) were evaluated. Visible vessel length and vessel sharpness were measured and visible coronary artery segments assessed. RESULTS: MR coronary artery imaging using MS-325 was successfully performed in 16 volunteers. One volunteer was excluded from the analysis because of trigger problems. SNR did not improve significantly after administration of MS-325 (14.1 vs. 14.6, p=NS), but CNR did (8.03 vs. 12.73, p<0.001). Image quality increased with MS-325 from 2.5+/-0.4 to 2.8+/-0.3 (p<0.05). Overall vessel length and vessel sharpness improved significantly after MS-325 administration (p<0.05). CONCLUSIONS: Whole-heart coronary MRA with the intravascular contrast agent MS-325 enables significant improvement in CNR, blood-myocardial contrast, image quality, visible vessel length, and vessel sharpness over non-contrast MRCA.

Anatomical and functional evaluation of myocardial bridging on the left anterior descending artery by cardiovascular magnetic resonance imaging.

A myocardial muscle bridge spans a segment of a major epicardial coronary artery that is located in the myocardium. This anatomic configuration can be responsible for angina pectoris, arrhythmias or even death. The current reference standard for diagnosis is conventional x-ray coronary angiography showing systolic compression of an epicardial vessel and the typical angiographic "milking effect." We report the case of a patient with myocardial bridging on the left anterior descending artery, in whom a combination of noninvasive high resolution display of the coronary artery lumen, visualization of the myocardium and functional assessment of blood flow during dobutamine stimulation by cardiovascular magnetic resonance imaging was performed.