Papillary muscle rupture without severe mitral regurgitation following percutaneous balloon mitral commissurotomy: a case report.

Background: Percutaneous transvenous mitral commissurotomy (PTMC) is the first-line therapy of clinically significant rheumatic mitral stenosis. While the procedure is generally safe, new onset or aggravation of mitral regurgitation (MR) may occur, mainly due to commissural splitting and, less frequently, to leaflet tear and chordal rupture. Papillary muscle rupture (PMR) is exceedingly rare in this setting. Case summary: A 74-year-old woman with a history of aortic valve replacement and prior rheumatic mitral commissurotomy presented for worsening exercise intolerance and exertional dyspnoea. Transthoracic echocardiography showed a mean pressure gradient of 10 mmHg and a mitral valve area of 1.0 cm², consistent with clinically significant mitral stenosis. Subsequent PTMC was complicated by anterolateral PMR. However, the resulting MR was unexpectedly only of mild-to-moderate severity. Because of residual mitral stenosis and persisting symptoms, surgical mechanical mitral valve replacement and tricuspid annuloplasty were performed 6 weeks after PTMC. Papillary muscle rupture was confirmed during surgery. Discussion: We herein describe the occurrence of PMR induced by PTMC; the resulting MR was unexpectedly of mild-to-moderate severity, as a result of extensive rheumatic lesions limiting valve mobility. This case challenges the dogma according to which PMR invariably leads to severe MR. This might not be necessarily the case when it occurs following PTMC.

Value of repeated measurements of lipoprotein (a) to assess cardiovascular risk: a retrospective study.

Background: High plasma concentrations of lipoprotein (a) [Lp(a)] are associated with an increased cardiovascular risk. Current guidelines recommend measurement of only a single Lp(a) in an individual's lifetime under specific circumstances to improve cardiovascular risk prediction. Accordingly, the question raised is the number of false positives and negatives missed through only a single measurement.Methods: All Lp(a) measurements between 2004 and March 2021 were retrieved from the laboratory database of the Erasme hospital. Only patients with repeated measurement were included. The first and subsequent Lp(a) measurement were compared. Two different cohorts were studied as a result of a change in Lp(a) determination methodology (n = 2049 and n = 309, respectively). The effects of a third Lp(a) measurement were assessed through binary analyses (n = 678). The 180 mg/dl (430 nmol/L) threshold recommended in the ESC guidelines was assessed first. Analysis was repeated for 100, 70 and 50 mg/dl thresholds of raised Lp(a) levels.Results: A low rate of false negatives (0.8%-1%) and false positives (0.6-0.3%) were revealed with two Lp(a) measurements. There was no difference in regards to the divergent Lp(a) thresholds nor the measurement of Lp(a) on two or three occasions.Conclusion: The present study showed Lp(a) determination to be reproducible. A single measurement is sufficient to assess if a patient exceeds various cut-off values of elevated Lp(a) levels.

Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality.

Background: Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value. Methods: Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC). Results: 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS). Discussion: Increased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia.

Quantification of Cardiac Kinetic Energy and Its Changes During Transmural Myocardial Infarction Assessed by Multi-Dimensional Seismocardiography.

Introduction: Seismocardiography (SCG) records cardiac and blood-induced motions transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions, and scalar parameters of kinetic energy can be computed. We speculate that AMI and revascularization profoundly modify cardiac kinetic energy as recorded by SCG. Methods: Under general anesthesia, 21 swine underwent 90 min of myocardial ischemia induced by percutaneous sub-occlusion of the proximal left anterior descending (LAD) coronary artery and subsequent revascularization. Invasive hemodynamic parameters were continuously recorded. SCG was recorded during baseline, immediately and 80 min after LAD sub-occlusion, and immediately and 60 min after LAD reperfusion. iK was automatically computed for each cardiac cycle (iK CC ) in linear (iK Lin ) and rotational (iK Rot ) dimensions. iK was calculated as well during systole and diastole (iK Sys and iK Dia , respectively). Echocardiography was performed at baseline and after revascularization, and the left ventricle ejection fraction (LVEF) along with regional left ventricle (LV) wall abnormalities were evaluated. Results: Upon LAD sub-occlusion, 77% of STEMI and 24% of NSTEMI were observed. Compared to baseline, troponins increased from 13.0 (6.5; 21.3) ng/dl to 170.5 (102.5; 475.0) ng/dl, and LVEF dropped from 65.0 ± 0.0 to 30.6 ± 5.7% at the end of revascularization (both p < 0.0001). Regional LV wall abnormalities were observed as follows: anterior MI, 17.6% (three out of 17); septal MI, 5.8% (one out of 17); antero-septal MI, 47.1% (eight out of 17); and infero-septal MI, 29.4% (five out of 17). In the linear dimension, i K L i n C C , i K L i n S y s , and i K L i n D i a dropped by 43, 52, and 53%, respectively (p < 0.0001, p < 0.0001, and p = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, i K R o t C C and i K R o t S y s dropped by 30 and 36%, respectively (p = 0.0006 and p < 0.0001, respectively), but i K R o t D i a did not change (p = 0.41). All the hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with the parameters of iK, except for the diastolic component. Conclusions: In this very context of experimental AMI with acute LV regional dysfunction and no concomitant AMI-related heart valve disease, linear and rotational iK parameters, in particular, systolic ones, provide reliable information on LV contractile dysfunction and its effects on the downstream circulation. Multidimensional SCG may provide information on the cardiac contractile status expressed in terms of iK during AMI and reperfusion. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future.

Assessment of left ventricular twist by 3D ballistocardiography and seismocardiography compared with 2D STI echocardiography in a context of enhanced inotropism in healthy subjects.

Ballistocardiography (BCG) and Seismocardiography (SCG) assess the vibrations produced by cardiac contraction and blood flow, respectively, by means of micro-accelerometers and micro-gyroscopes. From the BCG and SCG signals, maximal velocities (VMax), integral of kinetic energy (iK), and maximal power (PMax) can be computed as scalar parameters, both in linear and rotational dimensions. Standard echocardiography and 2-dimensional speckle tracking imaging echocardiography were performed on 34 healthy volunteers who were infused with increasing doses of dobutamine (5-10-20 µg/kg/min). Linear VMax of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear PMax of both SCG and BCG and the linear iK of BCG are the best predictors of the LV ejection fraction (LVEF) (p < 0.0001). This result is further confirmed by mathematical models combining the metrics from SCG and BCG signals with heart rate, in which both linear PMax and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear VMax of BCG, rather than the VMax of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. PMax and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.

SP-D and CC-16 Pneumoproteins' Kinetics and Their Predictive Role During SARS-CoV-2 Infection.

BACKGROUND: Surfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called "pneumoproteins" and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19). METHODS: This retrospective study included 87 patients admitted to an emergency department. Blood samples were collected on three time points (days 1, 5, and 14 from hospital admission). SP-D and CC-16 serum levels were determined, and univariate and multivariate analyses considering confounding variables (age, body mass index, tobacco use, dyspnea, hypertension, diabetes mellitus, neutrophil-to-lymphocyte ratio) were performed. RESULTS: Based on the multivariate analysis, SP-D level on D1 was positively and slightly correlated with subsequent development of ARDS, independent of body mass index, dyspnea, and diabetes mellitus. CC-16 level on D1 was modestly and positively correlated with fatal outcome. A rise in SP-D between D1 and D5 and D1 and D14 had a strong negative association with incidence of ARDS. These associations were independent of tobacco use and neutrophil-to-lymphocyte ratio. CONCLUSIONS: Overall, our data reveal that increase in SP-D levels is a good prognostic factor for patients with COVID-19, and that initial CC-16 levels correlated with slightly higher risk of death. SP-D and CC-16 may prove useful to predict outcomes in patients with COVID-19.

Sympathetic Effect of Auricular Transcutaneous Vagus Nerve Stimulation on Healthy Subjects: A Crossover Controlled Clinical Trial Comparing Vagally Mediated and Active Control Stimulation Using Microneurography.

INTRODUCTION: Auricular low-level transcutaneous vagus nerve stimulation (aLL-tVNS) has emerged as a promising technology for cardiac arrhythmia management but is still experimental. In this physiological study, we hypothesized that aLL-tVNS modulated the autonomic nervous balance through a reduction of sympathetic tone and an increase in heart rate variability (HRV). We investigated the muscle sympathetic nerve activity (MSNA) recorded by microneurography during vagally mediated aLL-tVNS and active control on healthy volunteers. METHODS: In this crossover, double-blind controlled study, healthy men (N = 28; 27 ± 4 years old) were assigned to aLL-tVNS applied to cymba and lobe (active control) of the right ear. Each participant was randomly allocated to the three sequences (5 Hz, 20 Hz, and active control-5 Hz) during one session. MSNA signal was recorded at rest, during voluntarily apnea and aLL-tVNS. Sympathetic activity was expressed as: 1) number of bursts per minute (burst frequency, BF) and 2) MSNA activity calculated as BF x mean burst amplitude and expressed as changes from baseline (%). RR intervals, HRV parameters and sympathetic activity were analyzed during 5 min-baseline, 10 min-stimulation, and 10 min-recovery periods. Mixed regression models were performed to evaluate cymba-(5-20 Hz) effects on the parameters with stimulation. RESULTS: During apnea and compared to baseline, BF and MSNA activity increased (p = 0.002, p = 0.001, respectively). No stimulation effect on RR intervals and HRV parameters were showed excepted a slightly increase of the LF/HF ratio with stimulation in the cymba-5Hz sequence (coef. ± SE: 0.76 ± 0.32%; p = 0.02). During stimulation, reductions from baseline in BF (Coef. ± SE: -4.8 ± 1.1, p < 0.001) was observed but was not statistically different from that one in the active control. Reduction of MSNA activity was not significantly different between sequences. CONCLUSION: Acute right cymba aLL-tVNS did not induce any overall effects neither on heart rate, HRV nor MSNA variables on healthy subjects when compared to active control. Interestingly, these findings questioned the role of active controls in medical device clinical trials that implied subjective endpoints.

Influence of sympathetic activation on myocardial contractility measured with ballistocardiography and seismocardiography during sustained end-expiratory apnea.

Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. BCG and SCG kinetic energies (KE) and their temporal integrals (iK) during a single heartbeat are computed in linear and rotational dimensions. Our aim was to test the hypothesis that iK from BCG and SCG are related to sympathetic activation during maximal voluntary end-expiratory apnea. Multiunit muscle sympathetic nerve traffic [burst frequency (BF), total muscular sympathetic nerve activity (tMSNA)] was measured by microneurography during normal breathing and apnea (n = 28, healthy men). iK of BCG and SCG were simultaneously recorded in the linear and rotational dimension, along with oxygen saturation ([Formula: see text]) and systolic blood pressure (SBP). The mean duration of apneas was 25.4 ± 9.4 s. SBP, BF, and tMSNA increased during the apnea compared with baseline (P = 0.01, P = 0.002,and P = 0.001, respectively), whereas [Formula: see text] decreased (P = 0.02). At the end of the apnea compared with normal breathing, changes in iK computed from BCG were related to changes of tMSNA and BF only in the linear dimension (r = 0.85, P < 0.0001; and r = 0.72, P = 0.002, respectively), whereas changes in linear iK of SCG were related only to changes of tMSNA (r = 0.62, P = 0.01). We conclude that maximal end expiratory apnea increases cardiac kinetic energy computed from BCG and SCG, along with sympathetic activity. The novelty of the present investigation is that linear iK of BCG is directly and more strongly related to the rise in sympathetic activity than the SCG, mainly at the end of a sustained apnea, likely because the BCG is more affected by the sympathetic and hemodynamic effects of breathing cessation. BCG and SCG may prove useful to assess sympathetic nerve changes in patients with sleep disturbances.NEW & NOTEWORTHY Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. Kinetic energies (KE) and their temporal integrals (iK) during a single heartbeat are computed from the BCG and SCG waveforms in a linear and a rotational dimension. When compared with normal breathing, during an end-expiratory voluntary apnea, iK increased and was positively related to sympathetic nerve traffic rise assessed by microneurography. Further studies are needed to determine whether BCG and SCG can probe sympathetic nerve changes in patients with sleep disturbances.

Ballistocardiography and seismocardiography detection of hemodynamic changes during simulated obstructive apnea.

OBJECTIVE: To investigate if modern seismocardiography (SCG) and ballistocardiography (BCG) are useful in the detection of hemodynamic changes occurring during simulated obstructive apneic events. METHODS: Forty-seven healthy volunteers performed a voluntary maximum Mueller maneuver (MM) for 10 s, and SCG and BCG signals were simultaneously taken. The kinetic energy of a set of cardiac cycles before and during the apneic episode was automatically computed from the rotational and linear channels of the SCG and BCG waveforms and its temporal integral (i K) was derived (unit of measure: microjoules per second (µJ·s)). The estimated transmural pressure (eP TM ) was assessed as the difference between systemic blood pressure and maximal inspiratory pressure (MIP). The Wilcoxon sign-rank test was used to evaluate differences in energy measurements between normal respiration and the loaded inspiration maneuver. Cardiac kinetic energies and the MIP produced during the MM were compared by linear regression analysis following log transformation in order to assess the correlation between variables. MAIN RESULTS: The [Formula: see text] during normal breathing increased from 1.1(0.8; 1.4) to 1.9(1.4; 4.3) µJ·s during MM (p < 0.001). Meanwhile, [Formula: see text] increased from 54 (31; 92) to 84 (44; 153) µJ·s, (p < 0.001). The [Formula: see text] and [Formula: see text] of a set of cardiac cycles during the MM were negatively associated with the MIP (r: -0.59, p < 0.001 and r: -0.53, p = 0.001 for [Formula: see text] and [Formula: see text], respectively). When eP TM was considered, this association became positive (r: +0.58, p < 0.001 and r:+0.60, p < 0.001, for [Formula: see text] and [Formula: see text], respectively). When the i K LIN was considered as the comparative factor, correlations with the MIP and eP TM were weak and insignificant. Men had higher values of i K than women. SIGNIFICANCE: Simulated obstructive apnea elicits large rotational i K swings, which are related to the intensity of the inspiratory effort and, as such, to the intensity of the left ventricular afterload. Computation of cardiac kinetic energy through BCG and SCG may shed further light on the impact of obstructive respiratory events on the cardiovascular system.

Publisher Correction: Accurate Detection of Dobutamine-induced Haemodynamic Changes by Kino-Cardiography: A Randomised Double-Blind Placebo-Controlled Validation Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Short halt in vaping modifies cardiorespiratory parameters and urine metabolome: a randomized trial.

Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules quickly cross the lung epithelium, we hypothesized that short-term cessation of vaping in regular users would completely clear aerosol deposit from the lungs and reverse vaping-induced cardiorespiratory toxicity. We aimed to assess the acute effects of vaping and their reversibility on biological/clinical cardiorespiratory parameters [serum/urine pneumoproteins, hemodynamic parameters, lung-function test and diffusing capacities, transcutaneous gas tensions (primary outcome), and skin microcirculatory blood flow]. Regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for 5 days before the session began. Multiparametric metabolomic analyses were used to verify subjects' protocol compliance. Biological/clinical cardiorespiratory parameters were assessed at the beginning of each session (baseline) and after acute vaping exposure. Compared with the nicotine- and nicotine-free-sessions, a specific metabolomic signature characterized the stop-session. Baseline serum club cell protein-16 was higher during the stop-session than the other sessions (P < 0.01), and heart rate was higher in the nicotine-session (P < 0.001). Compared with acute sham-vaping in the stop-session, acute nicotine-vaping (nicotine-session) and acute nicotine-free vaping (nicotine-free-session) slightly decreased skin oxygen tension (P < 0.05). In regular e-cigarette-users, short-term vaping cessation seemed to shift baseline urine metabolome and increased serum club cell protein-16 concentration, suggesting a decrease in lung inflammation. Additionally, acute vaping with and without nicotine decreased slightly transcutaneous oxygen tension, likely as a result of lung gas exchanges disturbances.

Modification of the mechanical cardiac performance during end-expiratory voluntary apnea recorded with ballistocardiography and seismocardiography.

OBJECTIVE: To assess if micro-accelerometers and gyroscopes may provide useful information for the detection of breathing disturbances in further studies. APPROACH: Forty-three healthy volunteers performed a 10 s end-expiratory breath-hold, while ballistocardiograph (BCG) and seismocardiograph (SCG) determined changes in kinetic energy and its integral over time (iK, J · s). BCG measures overall body accelerations in response to blood mass ejection into the main vasculature at each cardiac cycle, while SCG records local chest wall vibrations generated beat-by-beat by myocardial activity. This minimally intrusive technology assesses linear accelerations and angular velocities in 12 degrees of freedom to calculate iK during the whole cardiac cycle. iK produced during systole and diastole were also computed. MAIN RESULTS: The iK during normal breathing was 87.1 [63.3; 132.8] µJ · s for the SCG and 4.5 [3.3; 6.2] µJ · s for the BCG. Both increased to 107.1 [69.0; 162.0] µJ · s and 6.1 [4.4; 9.0] µJ · s, respectively, during breath-holding (p  = 0.003 and p  < 0.0001, respectively). The iK of the SCG further increased during spontaneous respiration following apnea (from 107.1 [69.0; 162.0] µJ · s to 160.0 [96.3; 207.3] µJ · s, p  < 0.0001). The ratio between the iK of diastole and systole increased from 0.35 [0.24; 0.45] during apnea to 0.49 [0.31; 0.80] (p  < 0.0001) during the restoration of respiration. SIGNIFICANCE: A brief voluntary apnea generates large and distinct increases in SCG and BCG waveforms. iK monitoring during sleep may prove useful for the detection of respiratory disturbances. ClinicalTrials.gov number: NCT03760159.

Accurate Detection of Dobutamine-induced Haemodynamic Changes by Kino-Cardiography: A Randomised Double-Blind Placebo-Controlled Validation Study.

Non-invasive remote detection of cardiac and blood displacements is an important topic in cardiac telemedicine. Here we propose kino-cardiography (KCG), a non-invasive technique based on measurement of body vibrations produced by myocardial contraction and blood flow through the cardiac chambers and major vessels. KCG is based on ballistocardiography and measures 12 degrees-of-freedom (DOF) of body motion. We tested the hypothesis that KCG reliably assesses dobutamine-induced haemodynamic changes in healthy subjects. Using a randomized double-blinded placebo-controlled crossover study design, dobutamine and placebo were infused to 34 volunteers (25 ± 2 years, BMI 22 ± 2 kg/m², 18 females). Baseline recordings were followed by 3 sessions of increasing doses of dobutamine (5, 10, 20 µg/kg.min) or saline solution. During each session, stroke volume (SV) and cardiac output (CO) were determined by echocardiography and followed by a 90 s KCG recording. Measured linear accelerations and angular velocities were used to compute total Kinetic energy (iK) and power (Pmax). KCG sorted dobutamine infusion vs. placebo with 96.9% accuracy. Increases in SV and CO were correlated to iK (r = +0.71 and r = +0.8, respectively, p < 0.0001). Kino-cardiography, with 12-DOF, allows detecting dobutamine-induced haemodynamic changes with a high accuracy and present a major improvement over single axis ballistocardiography or seismocardiography.

Obstructive sleep apnoea: from respiratory events to coronary microvascular dysfunction.

Obstructive sleep apnoea (OSA) is an emerging and independent risk factor for cardiovascular diseases; coronary artery disease (CAD) is higher in OSA patients, even in the absence of other traditional cardiovascular risk factors. There is little evidence to show abnormalities in coronary blood flow (CBF) and disorders in coronary vascular resistance (CVR), occurring during the obstructive respiratory event, suggesting coronary microvascular dysfunction (CMD) as a potential mechanism of ischaemic heart disease (IHD) OSA-as a related consequence.