Pressure-time Index Research Articles

COVID-19-Associated Multisystem Inflammatory Syndrome in Children and Cardiovascular Autonomic Control: A Prospective Cohort Study Nine Months after SARS-CoV-2 Infection.

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a severe pediatric complication during the SARS-CoV-2 pandemic, with potential long-term cardiovascular repercussions. We hypothesized that heart rate and blood pressure control at rest and during postural maneuvers in MIS-C patients, months after the remission of the inflammatory syndrome, may reveal long-term autonomic dysfunctions. Methods: We assessed 17 MIS-C patients (13 males; 11.9 ± 2.6 years, m ± SD) 9 months after acute infection and 18 age- (12.5 ± 2.1 years) and sex- (13 males) matched controls. Heart rate and blood pressure variability, baroreflex function, and hemodynamic parameters were analyzed in supine and standing postures. Results: MIS-C patients exhibited reduced heart rate variability, particularly in parasympathetic parameters during standing (pNN50+: 6.1 ± 6.4% in controls, 2.5 ± 3.9% in MIS-C; RMSSD: 34 ± 19 ms in controls, 21 ± 14 ms in MIS-C, p < 0.05), with no interaction between case and posture. Blood pressure variability and baroreflex sensitivity did not differ between groups except for the high-frequency power in systolic blood pressure (3.3 ± 1.2 mmHg2 in controls, 1.8 ± 1.2 mmHg2 in MIS-C, p < 0.05). The MIS-C group also showed lower diastolic pressure-time indices (DPTI) and systolic pressure-time indices (SPTI), particularly in standing (DPTI: 36.2 ± 9.4 mmHg·s in controls, 29.4 ± 6.2 mmHg·s in MIS-C; SPTI: 26.5 ± 4.3 mmHg·s in controls, 23.9 ± 2.4 mmHg·s in MIS-C, p < 0.05). Conclusions: Altered cardiovascular autonomic control may persist in MIS-C patients with, however, compensatory mechanisms that may help maintain cardiovascular homeostasis during light autonomic challenges, such as postural maneuvers. These results highlight the importance of assessing long-term cardiovascular autonomic control in children with MIS-C to possibly identify residual cardiovascular risks and inform targeted interventions and rehabilitation protocols.

The Protective Role of Resilience on Cardiovascular Health in Young Adults Exposed to Adverse Childhood Experiences

Background: Adverse childhood experiences (ACEs) are strong emotional or physical stressors that occur during sensitive developmental periods and are associated with reduced cardiovascular health (CVH). Resilience, or the psychological capacity of individuals to cope with adversity, has been recently shown to have a positive influence on CVH. Despite the dose-dependent detrimental impact of ACEs on CVH, it is unknown whether resilience exerts a protective cardiovascular effect against early stress. Thus, the purpose of this study was to investigate the impact that resilience may have on CVH in young adults who experienced ACEs. Methods: Eighteen young and apparently healthy adults (22±3 yo) with a history of severe ACE exposure (≥4) participated in this study and provided self-reported data about resilience. CVH was assessed non-invasively through transcutaneous arterial tonometry to evaluate arterial stiffness (pulse-wave velocity, PWV), myocardial oxygen demand (Systolic Pressure Time Index, SPTI), myocardial oxygen supply (Diastolic Pressure Time Index, DPTI) and myocardial perfusion (Subendocardial Viability Ratio, SEVR). Circulating biomarkers related to CVH were also evaluated (high-sensitive C-reactive protein, hsCRP). Results: Eleven participants reported high resilience (HR: resilience score≥95), while seven reported low resilience (LR: resilience score&lt;95). Young adults with high resilience presented with a significantly lower myocardial oxygen demand (SPTI; HR: 1866±111 vs. LR: 2227±117mmHg·s/min, p=0.047) and higher myocardial perfusion (SEVR; HR: 168±13 vs.LR: 127 ±9% , p=0.034) than those with low resilience and a positive association between SEVR and resilience was identified ( r=0.492; p=0.045). No differences in myocardial oxygen supply ( p=0.225) or arterial stiffness ( p=0.614) were observed between groups. However, circulating hsCRP was also significantly lower in the HR group than the LR (0.89±0.3 vs. 2.96±1 mg/dL, p=0.041) and negatively associated with resilience ( r=-0.511; p=0.051). Conclusions: Our data suggests that, among young and apparently healthy adults exposed to childhood adversity, those who are psychologically more resilient exhibit higher myocardial perfusion and overall better CVH than those less resilient despite a history of severe ACEs. These findings suggest that resilience may protect, at least partially, against the early impact of ACEs on CVH. Future studies are thus warranted to further explore the relationship between resilience and CVH. Supported in part by the Child Health Research Institute at VCU. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects.

Transdermal nicotine patches (TNPs), administering nicotine into the bloodstream through skin, have been widely used as nicotine replacement therapy, and exposure to nicotine can be detected by measurement of plasma cotinine concentration. In animal studies, nicotine treatment could increase the number of endothelial progenitor cells (EPCs), but the effect of TNPs on circulating EPCs and their activity in humans remained unclear. This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers. In parallel, pulse wave analysis (PWA) was applied to evaluate the vascular effect of TNP treatments. Twenty-one participants (25.8 ± 3.6 years old, 10 males) used TNP (nicotine: 4.2 mg/day) for 7 consecutive days. During the treatment, the CD34+ EPCs progressively increased in number. In addition, the number of EPCs positive for CD34/KDR, CD133, and CD34/CD133 were also increased on day 7 of the treatment. Furthermore, the early EPC colony-forming function and migration activity were increased with the plasma cotinine level positively correlating with change in colony-forming unit number. PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.

Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Abstract 15569: The Effect of Cardiac Pulmonary Nerve Stimulation on Cardiac Inotropy and Quality of Life in Patients With Acute Decompensated Heart Failure

Background: Acute decompensated heart failure (ADHF) results in over 1 million hospitalizations annually and involves neurohormonal disruption as well as autonomic dysfunction. Neuromodulation of the cardiac plexus using cardiopulmonary nerve stimulation (CPNS), currently being evaluated in clinical trials, is a novel strategy to treat ADHF. Methods: An interim analysis of 12 patients from ongoing trials was conducted. Patients were admitted with a principal diagnosis of ADHF (elevated NT-proBNP and LVEF≤50%) and underwent implant of a 16-electrode catheter (Figure 1A) in the right pulmonary artery, allowing cardiac plexus stimulation for 48 hrs. Stimulation was performed at 20 Hz frequency, 2.0 ms pulse width, and stimulation amplitude/vector (2.5-10 mA) to optimize cardiac function. LV pressure, arterial pressure, and ECG were concurrently recorded. An additional 12 patients not implanted were followed as a parallel standard of care (SOC) cohort. Results: There were no device-related serious adverse events (SAEs) during the index hospitalization or at 30 days post-discharge. Two SAEs unrelated to device occurred in 2 patients (clonic seizure and post-discharge pneumonia resulting in death). In response to stimulation, there was a statistical increase in maximum LV dP/dt (from 799 to 824 mmHg/sec, p&lt;0.01) and a statistical decrease in pressure time index (from 27.9 to 27.5 mmHg*sec, p&lt;0.05). Patients that received CPNS reported a significantly greater improvement in symptoms, function, and quality of life at 30 days (KCCQ-12; from 14.1 to 74.7, p&lt;0.0001) compared to patients in the SOC cohort (Figure 1B; 60.6 vs. 8.4, p&lt;0.05). Conclusion: In-hospital CPNS therapy is feasible and well-tolerated in ADHF patients. Stimulation increased cardiac inotropy, decreased energy consumption, and improved symptoms, function, and quality of life. Further investigation is required to determine if CPNS therapy leads to sustained improvement in clinical outcomes.

Diaphragmatic muscle function in term and preterm infants

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia—BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)—a measure of diaphragmatic strength, and the pressure–time index of the diaphragm (PTIdi)—a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi. Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function.What is Known:• The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively.• The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure–time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants.What is New:• Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue.• In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

SEX DIFFERENCES IN PULSE WAVE AND SUBENDOCARDIAL VIABILITY RATIO IN HYPERTENSIVE PATIENTS

Objective: Myocardial ischemia represents the main cause of morbidity and mortality in hypertensive patients in both women and men, although some difference in pathophysiology and in the exposure to risk factors may explain the lower global cardiovascular risk of women. Sex differences in the structure and function of the cardiovascular system may affect the aortic pressure wave and the functional balance in myocardial perfusion determined by central aortic pressure, which may lead to myocardial ischemia and type 2 myocardial infarction. Design and method: In a population of 318 treated hypertensive patients (162 females, 156 males) referring to a single Hypertension centre (University of Trieste, Italy), we measured peripheral blood pressure and performed arterial applanation tonometry (PulsePen, DiaTecne, Italy) to determine central blood pressure waveform, aortic pulse wave velocity (PWV), augmentation index (AIx), pulse wave separation analysis with timing and amplitude of forward (fT, fP) and backward reflected (bT, bP) waves, and the subendocardial viability ratio (SEVR), i.e. the ratio between diastolic and systolic pressure-time index, as a risk marker of myocardial ischemia. Results: Despite similar peripheral systolic and diastolic blood pressure values, heart rate and PWV between sexes, females showed a longer forward pressure wave duration (119.8±38.6 vs 105.0±30.4 ms, p&lt;0.0001) and lower amplitude (52.7±19,4 vs 57.1±19.3 mmHg, p = 0.039) compared to males. Backward pressure waved were similar in timing and amplitude between males and females. The difference in forward wave caused a marked higher AIx (19.5±12.4 vs 11.9±14.9, p&lt;0.0001) and a lower SEVR (101.6±24.4 vs 108.5±27.7, p = 0.018) in women compared to men. Conclusions: Hypertensive women and men showed significant differences in forward pressure wave, causing a significant increase in AIx and a decreased SEVR in women compared to men. This may have important implications in sex-specific risk and myocardial ischemia.

Вплив поліморфізма гена рецепторів ангіотензина ii типу 1 на ефективність антигіпертензивної терапії у хворих із гіпертонічною хворобою, які перенесли інфаркт міокарда за результатами довготривалого спостереження

The purpose of the study was to evaluate the effectiveness of antihypertensive therapy based on the data of daily blood pressure monitoring in patients with hypertension and a history of myocardial infarction, taking into account the A1166C polymorphism of the angiotensin II type 1 receptor gene, based on the results of long-term follow-up. Materials and methods. The study included 36 men with arterial hypertension of the 1st to 3rd degree who had suffered a myocardial infarction. The average age was 57.0 (52.0; 64.0) years, the experience of arterial hypertension – 6.3 (4.0; 15.0) years, the period after a myocardial infarction – 48.0 (12.0; 144.0) months. When determining the A1166C polymorphism of the angiotensin II type 1 receptor gene, patients were divided into 3 groups: group 1 consisted of 18 (50%) patients with the AA genotype, group 2 included 12 (33.3%) patients with the AС genotype, and group 3 – 6 (16.7%) patients with СС genotype of angiotensin II type 1 receptor gene. Daily blood pressure monitoring was carried out at the beginning of the study and after 38 months. Results and discussion. At the beginning of the study, based on the results of daily blood pressure monitoring, it was found that in the group as a whole, the levels of systolic blood pressure and diastolic blood pressure, the pressure load index – the diastolic blood pressure time index corresponded to the target values according to the median, but the pressure load indices for systolic blood pressure exceeded the normal range. Against the background of long-term antihypertensive therapy, a reliable decrease in systolic blood pressure levels was established for all time periods of the day, especially during the daytime. A significant decrease in the values of the pressure load indices was established – the time index of systolic blood pressure at daytime (delta -10.49%, which was -27.9%) and the area index of systolic blood pressure at daytime (delta -34.89 mm Hg x h, which was -32.0%) (p &lt;0.05). When analyzing the effectiveness of long-term antihypertensive therapy depending on the A1166C polymorphism of the angiotensin II type 1 receptor gene, it was established that the highest percentage of achieving the target blood pressure level (66.7%) in combination with the normalization of the circadian blood pressure rhythm was determined in patients with the AA genotype of the AGTR1 gene. Among patients with AC genotype, 33.3% reached the target blood pressure levels, but it was not possible to achieve normalization of blood pressure variability and pathological patterns of the circadian rhythm of blood pressure persisted, which are signs of a prognostically unfavorable course of the disease. Among patients with CC genotype of the AGTR1 gene, against the background of long-term treatment, 33.3% achieved the target level of blood pressure, in general, the group normalized the degree of nocturnal decrease in blood pressure, but only a decrease in the levels of systolic blood pressure and diastolic blood pressure during the day in combination with increased values of pressure load indices was observed, which indicates insufficiently effective control of arterial hypertension. Conclusion. During the long-term observation of patients with hypertension and a history of myocardial infarction, an assessment of the effectiveness of antihypertensive therapy was carried out taking into account the A1166C polymorphism of the AGTR1 gene based on the results of daily blood pressure monitoring

Blood pressure, arterial waveform, and arterial stiffness during hemodialysis and their clinical implications in intradialytic hypotension.

This study included 152 hemodialysis patients (mean age, 69 years; 34.2% female) and investigated serial changes in blood pressure (BP) and arterial stiffness indices during hemodialysis using an oscillometric device, SphygmoCor XCEL, and examined whether assessment of the arterial waveform has clinical implications for the management of intradialytic hypotension (IDH). Measurement was performed every 30 min during hemodialysis, and the threshold defining IDH was systolic BP (SBP) decrease ≥40 mmHg or a requirement for antihypotensive medication in all patients and ≥ the 75th percentile of maximum SBP decrease during hemodialysis (≥34 mmHg) in the subgroup without antihypotensive medication (n = 98). In all patients, a 1-standard deviation (SD) increase in the baseline subendocardial viability ratio (SEVR), an index of myocardial perfusion, was an independent predictor of IDH (odds ratio [OR] 0.43, p < 0.001). In the subgroup analysis, a serial change in SBP and all arterial waveform indices, including the augmentation index, augmented pressure (AP), and SEVR, during hemodialysis were greater for IDH than for non-IDH patients (all p < 0.01 by 2-way repeated-measures ANOVA), with the exception of heart rate (p = 0.40) and diastolic pressure time index (p = 0.21). Diabetes (OR 4.08), a 1-SD increase in ultrafiltration rate (OR 2.07), fractional shortening (OR 0.45), baseline SEVR (OR 0.36) and the first 1-h percent change in AP (OR 0.52) were independent predictors of IDH (all p < 0.05). In conclusion, impaired myocardial perfusion and increased arterial stiffness, particularly poor arteriolar responsiveness to acute dialysis-related changes, are associated with IDH, and predialysis SEVR evaluation can complement screening for IDH.

Myocardial remodeling and fibroblast growth factor in patients with resistant hypertension

Aim. To study the prevalence and severity of left ventricular hypertrophy (LVH), its relationship with fibroblast growth factor (FGF23) in patients with resistant hypertension (RH) depending on the effectiveness of multiagent antihypertensive therapy.Material and methods. The study included 92 patients diagnosed with RH. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, general laboratory tests, and the serum FGF23 level was determined.Results. According to ABPM results, patients were divided into following groups: 1st — controlled RH (n=44) and 2nd — uncontrolled (n=48) RH. The groups were comparable in sex, age, main clinical and anthropometric parameters. In group 2, the main parameters of ABPM were higher. There were no differences in general laboratory tests, In the group of uncontrolled RH, the level of FGF23 was higher — 11,7 [8,5; 15,4] pmol/ml vs 9,2 [7,1; 11,6] pmol/ml in the 1st group (p=0,0036). According to echocardiography, a comparable violation of left ventricular (LV) diastolic function, an increase in left atrial size, LV mass (LVM) and LVM index were found. In patients of the 2nd group, large values of interventricular septal thickness were revealed — 1,3 [1,2; 1,4] cm vs 1,2 [1,1; 1,3] cm in the 1st group (p=0, 0043) and relative LV wall thickness (LVWT) — 0,50 [0,48; 0,53] vs, 0,45 [0,43; 0,50] in the 1st group (p&lt;0,0001). In the 1st and 2nd groups, concentric LVH was more common (18 (41%) patients in the 1st and 26 (54,1%) in the 2nd (p=0,044) groups) than eccentric LVH (15 (34,1%) and 13 (27,1%) patients in the 1st and 2nd groups, respectively). Correlation analysis revealed a positive relationship between pulse pressure and HTN duration (r=48, p=0,02) and FGF23 level (r=0,62, p=0,004). The LVM index was positively associated with the diastolic pressure-time index (BP) (r=51, p=0,02). A positive correlation was found between relative LVWT and pulse pressure (r=0,64, p=0,02) and a negative relationship with the duration of regular antihypertensive therapy (r=47, p=0,04), A strong relationship was found between LVEF and FGF23 levels (r=0,75, p=0,005).Conclusion. For patients with uncontrolled resistant hypertension, an increase in pulse pressure and myocardial remodeling in the form of concentric hypertrophy are more characteristic. FGF23 is significantly higher in uncontrolled RH and is positively associated with pulse pressure and relative LVWT.

Abstract 10550: Higher Endocardial Viability Ratio is Associated With Improved Left Ventricular Function After Transcatheter Aortic Valve Replacement

Introduction: Both LV dysfunction and AS lead to an increase in LVEDP, a decrease in oxygen delivery to cardiac muscle, and ultimately a decrease in the EVR. Hypothesis: We hypothesized that patients with low EVR would have less significant recovery of LV function after TAVR. Methods: Patients with LVEF &lt;40% and severe AS undergoing TAVR at the University of Virginia (UVA) between 2012 and 2019 were retrospectively reviewed. EVR was calculated by dividing the diastolic pressure time index (DPTI) [(Diastolic blood pressure – LVEDP) x (60seconds/ heart rate – 0.2 seconds)] by the tension time index (TTI) [systolic pressure x 0.2 seconds] using catheter-derived hemodynamics prior to TAVR. LVEF and mAG values were obtained from TTE measurements done for procedural planning and at, or closest to, 1-year follow-up. The patients were divided into cohorts based on EVR above or below 0.7, a value indicative of subendocardial ischemia. Mean change in LVEF was evaluated between these two groups (Figure [1] and Table [1]) and multivariable regression was performed using pre-procedural LVEF, EVR, and change in mean aortic gradient as shown in Table [2]. Results: 128 patients that underwent TAVR had a LVEF &lt;40%. 85 patients (32.5% female) had complete invasive hemodynamic and echocardiographic data. The mean change in post-TAVR LVEF in the lower subgroup was &lt;5% with a standard deviation of 12.5. In patients with EVR &gt;0.7 there was improvement of LVEF of &gt;10% with a standard deviation of 10.8. Two-tailed t-testing was performed with a corresponding p-value of 0.0181. Multivariable regression on pre-procedural LVEF, pre-procedural EVR, and change in mean AG were all statistically significant. Conclusion: EVR &gt;0.7 is associated with greater improvement in LV function in advanced heart failure patients after TAVR.

Numerical Analysis on Effect of Coronary Supply-Demand Equilibrium on Varying Coronary Blockage and Stress Conditions.

In this paper, we present a computational fluid dynamic (CFD) analysis to capture the effect of physical stress and stenosis severity in coronary arteries leading to changes in coronary supply demand oxygen equilibrium. We propose a coupled Od-3d coronary vessel model to predict the variation in flow dynamics of coronary as well as arterial system, modeled using an in-silico model replicating cardiovascular hemodynamics. CFD simulation were solved using subject specific CT scan for coronary and arterial flow and pressure along with metrics related to arterial wall shear stress. Simulations were performed for three heart rates (75, 90 and 120 bpm) and four stenosis states representing different stages of Coronary artery disease (CAD) namely healthy, 50%, 75%, 90% blockage in left anterior descending artery (LAD). Myocardial oxygen supply demand equilibrium were calculated for each cases using hemodynamic surrogate markers naming Diastolic pressure time index for supply and Tension time index for demand. The proposed 0d-3d coupled hemodynamic model of the coronary vessel bed along with supply-demand equilibrium estimated for different stress level and stenosis severity may provide useful insights on the dynamics of CAD manifestation and predict vulnerable regions in coronary bed for early screening and interventions.

Validation of a non-invasive pressure–time index of the inspiratory muscles in spontaneously breathing newborn infants

To validate the pressure–time index of the inspiratory muscles as a non-invasive index of inspiratory muscle function in spontaneously breathing infants by comparing it against the gold-standard pressure–time index of the diaphragm. Prospective observational cohort study of consecutive infants breathing unsupported in room air in a tertiary neonatal intensive care unit, studied prior to discharge from neonatal care. The invasive pressure–time index of the diaphragm was calculated using a transdiaphragmatic dual-pressure catheter that measured transdiaphragmatic pressure by subtraction of the oesophageal from the gastric pressure. The non-invasive pressure–time index of the inspiratory muscles was calculated using pressure measurements at the level of the mouth via a differential pressure transducer connected to a face mask. Both indices were calculated as the product of the ratio of the mean inspiratory pressure divided by the maximum inspiratory pressure and the ratio of the inspiratory time divided by the total time of a respiratory cycle. One hundred and thirty infants (79 male) were included with a mean (SD) gestational age of 35.2 (3.2) weeks, studied at a median (IQR) postnatal age of 9 (6–20) days. The mean (SD) pressure–time index of the diaphragm was 0.063 (0.019) and the mean (SD) pressure–time index of the inspiratory muscles was 0.065 (0.023). The correlation coefficient for the two indices was 0.509 (p < 0.001). The mean (SD) absolute difference between the pressure–time index of the inspiratory muscles and pressure–time index of the diaphragm was 0.002 (0.021). In convalescent infants, the non-invasive pressure–time index of the inspiratory muscles had a moderate degree of correlation with the invasively derived pressure time index of the diaphragm measured with a transdiaphragmatic catheter.

Resveratrol Reduces Arterial Stiffness and Improves Functional Capacity in Patients with COPD

IntroductionChronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death worldwide and is strongly associated with the development of cardiovascular disease (CVD). Large artery stiffening is recognized as a major CVD risk factor that contributes to diminished myocardial blood supply and reduced functional capacity, a marker of disease severity in COPD. Elevated oxidative stress plays a pivotal role in the etiology of both COPD and CVD. Apart from the body’s endogenous ability to counteract oxidative stress, the consumption of exogenous antioxidants also enhances the capacity to scavenge free radicals and reduce arterial stiffness. Whether or not antioxidants can reduce arterial stiffness and improve functional capacity in patients with COPD, however, has yet to be elucidated.PurposeThis study sought to test the hypothesis that oral resveratrol, a powerful antioxidant, will reduce arterial stiffness and improve functional capacity in patients with COPD.MethodsTen patients with COPD (GOLD Stage II‐IV) participated in this study and completed 6 weeks of oral resveratrol (500 mg/daily) or placebo (PLC) treatment. Arterial stiffness was evaluated via tonometry (SphygmoCor) before and after RES or PLC to assess augmentation index (AIx), AIx normalized to a heart rate of 75 beats per minute (AIx75), and diastolic pressure time index (DPTI). Functional capacity was measured via six‐minute walk test to evaluate distance walked.ResultsA single dose of RES significantly (p&lt;0.01) improved markers of arterial stiffness (AIx75: ∆RES=‐8±2% vs. ∆PLC=‐4±2%) while increasing myocardial perfusion (DPTI: ∆RES=158±79 mmHg vs. ∆PLC=‐23±18 mmHg p=0.04). No changes (p=0.171) in functional capacity were observed after a single dose of RES or PLC. However, six weeks of RES significantly (p=0.01) reduced AIx75 (∆RES=‐9±3% vs. ∆PLC=‐3±2%), while it improved myocardial perfusion (DPTI: ∆RES=166±85 mmHg vs. ∆PLC=‐36±18 mmHg; p=0.04) and distance walked (∆RES=25±13m vs. ∆PLC=‐2±4m; p=0.04).ConclusionFor the first time, we have identified that the antioxidant resveratrol reduces markers of arterial stiffness and improves myocardial perfusion in patients with COPD. In addition, six weeks of daily intake of this natural antioxidant also improved functional capacity in this population. Future studies are warranted to investigate the long terms effects of resveratrol in cardiovascular health in patients with COPD.

Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat's Heart.

BackgroundCisplatin is a common anticancer drug with potential cardiac and renal toxicities. Rutin, a natural compound present in various medicinal plants, has been shown to protect against chemotherapy-induced toxicities. In this study, we explored the protective effect of rutin against the dose-dependent cardiotoxic effects of cisplatin such as perfusion pressure, histopathologic effect on the myocardium, and oxidative stress in isolated perfused rat hearts.MethodologyThe cardiotoxic effects of cisplatin were studied at three dosages (1, 7, and 14 mg/L) in isolated perfused rat hearts. The dose-dependent, cisplatin-induced toxic effects on left ventricular pressure (LVP), heart rate (HR), dp/dt (maximum), dp/dt (minimum), perfusion pressure, pressure-time index, contractility index, and duration of diastole were assessed. The effects of cisplatin were measured one minute before perfusion of cisplatin and 60 minutes after perfusion of the isolated rat hearts.ResultsCisplatin (1-14 mg/L) caused a significant (p < 0.05) dose-dependent reduction in LVP. The percentage LVP values reduced from 94 ± 9 (control untreated hearts) to 70 ± 6, 69 ± 5, and 65 ± 4 in hearts treated with 1, 7, and 14 mg/L of cisplatin, respectively. Similarly, cisplatin at similar doses caused a marked reduction in the values of dp/dt (maximum), dp/dt (minimum), and pressure-time index in isolated rat hearts. The respective percentage values of these parameters compared to those of untreated hearts were significantly reduced from 101 ± 7 to 72 ± 5, 92 ± 8 to 69 ± 4, and 92 ± 12 to 57 ± 7 in hearts treated with 14 mg/L of cisplatin. Perfusion of hearts with rutin trihydrate (1 µM/L) 10 minutes before administration of cisplatin and throughout the experiment attenuated the detrimental effects of cisplatin on cardiac functions in isolated rat hearts (p < 0.05). In addition, cisplatin-induced degeneration and necrosis of cardiac muscle cells reduced with the concurrent administration of rutin and restored normal heart histology. Moreover, cisplatin-induced reduction in glutathione and increased level of malondialdehyde in the myocardium was reversed by concurrent administration of rutin in isolated rat hearts.ConclusionsCisplatin produced a dose-dependent impairment of several parameters of cardiac function such as LVP, contractility index, and pressure-time index. It caused histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were suppressed by rutin trihydrate, suggesting the potential protective effects of rutin against cisplatin-induced cardiotoxicity. Rutin trihydrate also improved the reduced glutathione contents and suppressed the malondialdehyde contents in the cardiac tissue of isolated rat hearts, suggesting that the observed beneficial effects of rutin trihydrate in this study could be related to its antioxidant properties.

Abstract 11969: Endocardial Viability Ratio is Associated With Survival in Advanced Heart Failure Patients

Introduction: Myocardial oxygen supply is an important determinant of cardiac function. The Endocardial Viability Ratio (EVR), a measure of myocardial oxygen supply-demand balance, is calculated as a ratio of the diastolic pressure time index [(diastolic blood pressure - left ventricular end diastolic pressure) x (60 sec/heart rate - 0.2 sec)] and tension time index [systolic pressure x 0.2 sec]. We hypothesized that low EVR would be associated with adverse events in patients with heart failure (HF). Methods: EVR was calculated in the invasive arm of the ESCAPE trial in patients with available discharge blood pressure, pulmonary arterial wedge pressure, and heart rate as the ratio of the diastolic pressure time index (a measure of coronary blood supply) and tension time index (a measure of myocardial oxygen demand). Kaplan-Meier analysis and Cox proportional hazards regression was used to assess associations with EVR and a composite death endpoint including cardiac transplantation and left ventricular assist device implantation. Results: Among 143 patients (56.9 ± 13.3 years, 30.1% female), the median EVR was 1.168 (IQR 0.923-1.398). Survival during 180 days of follow-up was worse in patients with EVR below the median (p=0.0004) (Figure panel 1A). Among the 10 patients with EVR &lt; 0.7, considered to represent subendocardial ischemia, 50% reached this endpoint within 100 days (p=0.01 versus remaining patients) (Figure 1B). An increase of 0.1 in EVR was associated with an 18% relative risk reduction for this endpoint (HR 0.82, 95% CI 0.74-0.91, p=0.0002), while an increase of 0.5 in EVR was associated with a 62% relative risk reduction (HR 0.38, 95% CI 0.22-0.64, p=0.002). Conclusion: Decreased EVR, a marker of myocardial oxygen supply, is associated with adverse events in advanced HF patients. Further studies on the prognostic utility of EVR in HF are needed.

Abstract 12643: Sub-Endocardial Viability Index and Survival in the HF-ACTION Trial

Introduction: Myocardial perfusion relative to left-ventricular workload may be estimated by the sub-endocardial viability index (SVI). This can be calculated myocardial oxygen supply-demand balance, which is the ratio of diastolic to systolic pressure-time indices, i.e. [(DBP - PAWP) x (60sec/heart rate - 0.2sec)] / (SBP x 0.2sec), assuming fixed 0.2sec for systole. Low SVI indicates reduced sub-endocardial perfusion and was hypothesized to associate with negative outcomes in HFrEF patients. Methods: HF-ACTION was a randomized trial evaluating the efficacy of aerobic exercise training and usual care versus usual care in chronic HFrEF patients. SVI was calculated in HF-ACTION trial patients with complete hemodynamic data. PAWP was calculated using the Nagueh formula from echocardiographic-derived measurements ([PAWP=1.24*(E/e’) +1.9] with e’ = [(e’lateral + e’septal)/2]). The association of SVI with the combined endpoint of death or hospitalization, as well as all-cause death, was assessed. Results: Of 2331 patients in HF-ACTION, 807 had complete data. The mean SVI was 1.59 ± 0.47. The Cox proportional hazards model for the combined endpoint and all-cause death had HR of 0.66 per unit increase in SVI (p&lt;0.00001, 95% CI 0.55-0.79) and 0.67 (p=0.04, 95% CI 0.46-0.98), respectively. Survival during 4 year follow-up was worse below the mean SVI (p=0.0073) ( Figure 1) . In 26 patients below the critical sub-endocardial ischemia SVI of 0.7, survival was worse (p=0.0013) ( Figure 2) . Conclusion: Reduced SVI, a metric of the adequacy of sub-endocardial perfusion, is associated with negative outcomes in HFrEF patients. Figure 1. Figure 2.

Clinical and instrumental profile of patients with stage II essential hypertension with different forms of extrasystoles according to the level of apelin-13

Annotation. Essential hypertension (EH) is one of the leading causes of disability and mortality among cardiovascular diseases, so today new metabolic markers of cardiovascular risk are being actively studied. One of them is apelin-13. Objective – to evaluate the clinical and instrumental profile of patients with stage II hypertension with different forms of extrasystoles and different neurohumoral background – conditionally high/low serum apelin-13 levels. 156 patients with stage II essential hypertension were examined. 124 of them had frequent symptomatic extrasystoles, 32 patients had no arrhythmias and were considered to the comparison group. 30 practically healthy normotensive persons were considered to the control group. All patients underwent a complete clinical and anthropometric examination, blood pressure measurement, automatic daily blood pressure monitoring, daily electrocardiogram monitoring, echocardiography and the assessment of serum apelin-13 level. For statistical analysis, the procedure of non-linear data estimation was chosen, namely logistic regression or logit model. To form the basic statistical matrix of the analysis, we used clinical-instrumental and laboratory indicators, which passed a preliminary correlation analysis of Spearman with the level of apelin-13 serum and found a significant correlation (p&lt;0.05). In the course of the logistic analysis at the final model, which allowed to predict “background of apelin” in patients with stage II EH entered 4 independent factors that revealed statistically significant (p&lt;0.05) correlations with the initial parameter: the value of the systolic arterial pressure time index in%, the index of the left atrium in mm/m2, the average number of ventricular extrasystoles for 1 hour and the level of total cholesterol in plasma in mmol/l. The last indicator showed the least informativeness in predicting of the apelin-13 serum level. Interpreting the data of the obtained logit regression model, it should be said that in patients with EH of increasing the value of the systolic arterial pressure time index, the index of the left atrium and the average value of ventricular extrasystoles during 1 hour and decrease total cholesterol level in plasma increase the probability of determining relatively low (&lt;920 pg/ml) and at the same time reduce the probability of determining a relatively high (≥920 pg/ml) level of apelin serum. These data also show that the highest informativeness in predicting the level of apelin-13 in patients with EH was the total number of ventricular extrasystole per hour. So, a high “apelin background” (≥920 pg/ml) in patients with EH will be accompanied by a benign course of the disease, so an increase serum apelin-13 in patients with EH should be considered as positive neurohumoral changes that promote cardioprotection, improve prognosis course of the disease and reduce cardiovascular risk.

The Role of Aortic Stiffness Parameters in Evaluating Myocardial Ischemia.

BackgroundArterial stiffness is a process resulting in deterioration of hemodynamic function of the aorta, a decrease in its compliance and elasticity, caused by the proportional change of components of the extracellular matrix. Although many researches have been done to determine the etiologies of myocardial ischemia in the absence of obstructive coronary artery disease, none of them has investigated the relation between the parameters of aortic stiffness and the myocardial ischemia documented by the exercise stress test. The present cross-sectional study aimed to investigate the difference of aortic stiffness parameters between the groups separated by exercise stress test result as positive and negative ischemic findings in the absence of obstructive coronary artery disease.MethodsThe present study included 79 patients who were admitted to Istanbul Faculty of Medicine, Department of Cardiology with complaint of chest pain. Forty patients (21 women and 19 men) have ischemic findings on the exercise electrocardiography (ECG) test and 39 patients (20 women and 19 men) have normal exercise ECG results. The patients who have positive exercise ECG findings underwent coronary angiography and all the patients had non-obstructive coronary artery disease. Demographic features (age, sex and comorbidities) were statistically similar between the groups. Aortic stiffness measurements (pulse wave velocity, pulse pressure, aortic augmented pressure, augmentation index, systolic pressure-time index, diastolic pressure-time index and subendocardial viability ratio) were done with tonometric methods.ResultsThere was no significant difference between the two groups in terms of the aortic stiffness parameters. Systolic blood pressure (P = 0.33), diastolic blood pressure (P = 0.24), pulse pressure (P = 0.60), systolic pressure-time index (P = 0.10), diastolic pressure-time index (P = 0.91), subendocardial viability ratio (P = 0.19), aortic augmented pressure (P = 0.87), augmentation index (P = 0.58) and pulse wave velocity (P = 0.56) were detected between the two groups. Biochemical parameters were found similar between the two groups. Only low-density lipoprotein levels were slightly higher in patients with negative exercise stress test result (139 vs. 123 mg/dL, P = 0.02).ConclusionThere is no finding supporting that the aortic stiffness identifies the patients with non-obstructive coronary artery disease but with signs of myocardial ischemia and further investigation of other causes of myocardial ischemia is required.

Resistance Exercise on Pulse Wave Reflection and Arterial Stiffness Between Trained and Untrained Individuals

Pulse wave reflection [augmentation index (AIx), augmentation pressure (AP)], and arterial stiffness [pulse wave velocity (PWV)] are indicative of cardiovascular health. Acute resistance exercise (RE) alters pulse wave reflection, and arterial stiffness, but responses in resistance-trained individuals is unclear. PURPOSE: To examine the responses in pulse wave reflection and arterial stiffness after RE in resistance-trained (RT) versus untrained (UT) individuals. METHODS: Twenty-one (RT: n=14; UT: n=7) individuals volunteered. Pulse wave reflection and arterial stiffness were collected at rest, and 10min following a control, or RE consisting of 3 sets of 10 repetitions at 75% 1-repetition maximum (1RM) on the leg press, lat pulldown, leg extension, chest press and leg curl. A 2x2x2 ANOVA was used to examine group (RT, UT) differences across conditions (RE, control) and time (Rest, Recovery). RESULTS: The groups were similar (p>0.05) for age, height, and BMI, but not weight (p<0.05). The 1RMs for all exercises, except leg extension (p=0.26), were different between groups. At rest, the groups were statistically different for the tension-time index [TTI (RT: 1999±282ms; UT: 2192±209ms, p=0.04)], diastolic pressure-time index [DPTI (RT: 2817±316ms; UT: 3047±171ms, p=0.003)], and PWV (RT: 5.5±0.7m/s; UT: 6.3±0.4m/s, p=0.0001). There were significant time by condition interactions for aortic pulse pressure (Rest: 34±6mmHg; Recovery: 37±8mmHg, p=0.01), AP (Rest: 5±3mmHg; Recovery: 6±5mmHg, p=0.003), AIx normalized at 75bpm (Rest: 8.7±12.6%; Recovery: 16.4±6.0%, p=0.004), and TTI (Rest: 2084.6±273.4ms; Recovery: 2760.9±463.3ms, p=0.0001) such that they increased during recovery, compared to rest after RE, and the control. There were condition by time interactions for DPTI (Rest: 2889.6±297.0ms; Recovery: 2394.9±458.3ms, p=0.005) and subendocardial viability ratio SEVR (Rest: 138.4±19.3%; Recovery: 86.6±33.0%, p=0.006) such that they increased after acute resistance exercise, compared to rest and the control. There were no significant changes in arterial stiffness. CONCLUSION: These data suggest that resistance-trained individuals have reduced workload of the heart and lower arterial stiffness at rest, but are similar to untrained individuals after acute resistance exercise.