Serum NT-Pro-BNP versus Noninvasive Bedside Inotropic Index in Paediatric Shock: A Contest of Myocardial Performance in Response to Fluid Loading

Background. Mild elevation of serum amino-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is associated with myocardial dysfunction. A significantly lower Smith–Madigan inotropic index (SMII) has been shown to accurately represent cardiac contractility among heart failure subjects. We aim to monitor the effect of fluid resuscitation on cardiac function among paediatric patients by measuring serum NT-pro-BNP and SMII. Methods. This is an observational study on 70 paediatric shock patients. NT-pro-BNP and noninvasive bedside haemodynamic monitoring were done by using an ultrasonic cardiac output monitor (USCOM, USCOM, Sydney, Australia). The presence of cardiac diseases was excluded. SMII was obtained from the USCOM. An increase in the stroke volume index (SVI) of ≥15% indicates fluid responders. Measurements were taken before and after fluid loading. Results. Preloading NT-pro-BNP and SMII category were significantly different between the fluid responsiveness group, p = 0.001 and p = 0.004 , respectively. Higher median NT-pro-BNP (preloading NT-pro-BNP of 1175.00 (254.50–9965.00) ng/mL vs. 196.00 (65.00–509.00) ng/mL, p = 0.002 ) was associated with fluid nonresponders (subjects >12 months old). Preloading NT-pro-BNP <242.5 ng/mL was associated with fluid responders (AUC: 0.768 (0.615–0.921), p = 0.003 ), 82.1% sensitivity, and 68.7% specificity for subjects >12 years old. Delta NT-pro-BNP in fluid responders (15.00 (−16.00–950.00) ng/mL) did not differ from fluid nonresponders (505.00 (−797.00–1600.00) ng/mL), p = 0.456 . Postloading SMII >1.25 W·m−2 was associated with fluid responders (AUC: 0.683 (0.553–0.813), p = 0.011), 61.9% sensitivity, and 66.7% specificity, but not preloading SMII. Fluid responders had a higher mean postloading SMII compared to nonresponders (1.36 ± 0.38 vs. 1.10 ± 0.34, p = 0.006 ). Conclusion. Higher NT-pro-BNP and lower SMII in the absence of cardiac diseases were associated with poor response to fluid loading. The SMII is affected by low preload conditions.

Cardiac Stroke Volume Index Is Associated With Early Neurological Improvement in Acute Ischemic Stroke Patients

Early neurological improvement as assessed with the NIH stroke scale (NIHSS) at 24 h has been associated with improved long-term functional outcomes following acute ischemic stroke (AIS). Cardiac dysfunction is often present in AIS, but its association with outcomes is incompletely defined. We performed a pilot study to evaluate the association between non-invasively measured cardiac parameters and 24-h neurological improvement in prospectively enrolled patients with suspected AIS who presented within 12 h of symptom-onset and had an initial systolic blood pressure&gt;140 mm Hg. Patients receiving thrombolytic therapy or mechanical thrombectomy were excluded. Non-invasive pulse contour analysis was used to measure mean arterial blood pressure (MAP), cardiac stroke volume index (cSVI), cardiac output (CO) and cardiac index (CI). Transcranial Doppler recorded mean middle cerebral artery flow velocity (MFV). We defined a decrease of 4 NIHSS points or NIHSS ≤ 1 at 24-h as neurological improvement. Of 75 suspected, 38 had confirmed AIS and did not receive reperfusion therapy. Of these, 7/38 (18.4%) had neurological improvement over 24 h. MAP was greater in those without improvement (108, IQR 96–123 mm Hg) vs. those with (89, IQR 73–104 mm Hg). cSVI, CO, and MFV were similar between those without and with improvement: 37.4 (IQR 30.9–47.7) vs. 44.7 (IQR 42.3–55.3) ml/m2; 5.2 (IQR 4.2–6.6) vs. 5.3 (IQR 4.7–6.7) mL/min; and 39.9 (IQR 32.1–45.7) vs. 34.4 (IQR 27.1–49.2) cm/s, respectively. Multivariate analysis found MAP and cSVI as predictors for improvement (OR 0.93, 95%CI 0.85–0.98 and 1.14, 95%CI 1.03–1.31). In this pilot study, cSVI and MAP were associated with 24-h neurological improvement in AIS.

Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients

Background: Aging and frailty make the elderly patients susceptible to hypotension following spinal anesthesia. The systemic hemodynamic effects of spinal anesthesia are not well known. In this study, we examine the systemic hemodynamic effects of fractional spinal anesthesia following intermittent microdosing of a local anesthetic and an opioid.Methods: We included 15 patients aged over 65 with considerable comorbidities, planned for emergency hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. Invasive mean arterial pressure (MAP), cardiac index, systemic vascular resistance index, heart rate and stroke volume index were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15µg were administered with 25 minutes in between. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHgResults: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.003-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes after the first dose. Cardiac index, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the first dose, none of the systemic haemodynamic variables were affected.Conclusion: Fractional spinal anesthesia causes a low incidence of hypotension, induced mainly by a systemic venodilation, causing a decrease in venous return and fall in cardiac output. Our results show that fractional spinal anesthesia is a safe technique from a hemodynamic point of view and is probably underutilized in high-risk, elderly hip fracture patients

Effect of heart rate control with amiodarone infusion on hemodynamic and clinical outcomes in septic shock patients with tachycardia: a prospective, single-arm clinical study

Background Keeping the heart rate within the normal range has improved the survival of septic shock patients. Amiodarone could target the underlying pathophysiology of sepsis-induced tachycardia. This study aimed to determine whether amiodarone is effective in controlling the heart rate in critically ill patients with septic shock and sustained tachycardia who were receiving vasopressor. Methods In this prospective, single-arm cohort study, 46 patients with septic shock and tachycardia were enrolled to receive a loading dose of amiodarone 150 mg, then continuous infusion of 1 mg/min. The primary outcome was the ability of amiodarone in rate control lower than 95 beats per minute (BPM) and maintaining it during 24-h study period. We also recorded the effect of amiodarone on hemodynamic indices as the secondary outcomes. Results The results of the present study indicated a significant decrease in HR in septic shock patients for amiodarone, from 121.0 (116.5, 140.0) at baseline to 91.5(89.3, 108.0) at the end of the study period (p < 0.001). During the study period, a total of 26 (56.52%) of patients achieved the target heart rate lower than 95 BPM and maintained it during study period. Amiodarone decreased HR by 22.8 ± 13.7. While receiving amiodarone infusion, the values for heart rate, mean arterial pressure, cardiac index, norepinephrine infusion rate, and stroke volume index changed significantly between amiodarone initiation and 24-h follow-up (P < 0.001). Amiodarone was well tolerated, because this anti-arrhythmic agent did not increase the need for vasopressor and none of the patients experienced episodes of refractory hypotension. Conclusion This study showed that amiodarone infusion successfully reduced the heart rate in sepsis-induced tachycardia. The patients had improved hemodynamic state as indicated by an increase in cardiac index and SVI.

Estimation of possible candidates for ivabradine in rural Japan and investigation of their clinical characteristics

Background In Japan, ivabradine is indicated in patients with heart failure (HF) with sinus rhythm and a resting heart rate (HR) ≥75/min under standard treatment. Particularly, it is effective for HF with reduced left ventricular ejection fraction (LVEF). However, elderly people have a higher incidence of atrial fibrillation than young people, and their sinus node function is further deteriorated, resulting in a lower intrinsic HR. In addition, Japan is an ultra-aging society, especially in the countryside; therefore, the target patients for ivabradine may be limited in these regions. Purpose We sought to estimate the possible candidates for ivabradine and investigate their clinical characteristics in our hospital located in rural Japan. Method and results We retrospectively studied 14733 consecutive patients who were suspected heart disease who underwent echocardiography between January 2006 and October 2018 in Kitaishikai Hospital located in Ozu city (Proportion of the population aged ≥65 years: 34%, in 2015) and did not take ivabradine treatment. Of these, 187 patients with hemodynamically stable condition whose E/A ratio was measured and met the criteria of LVEF &lt;40% and HR ≥75 /min were confirmed. Of these, 153 patients reached HR &lt;75 /min with additional intensive medication within one year after the index echocardiography (Controlled group; mean HR: 82 to 62/min). The remaining 34 patients with uncontrolled HR (Uncontrolled group; mean HR: 84 to 82/min) were considered possible candidates for ivabradine (34/14733: 0.23%, 2.6 patients per year; median age, 74 years; male, 56%; median LVEF, 32%; ischemic cardiomyopathy, 53%). In the comparison of clinical and echocardiographic parameters in these two groups, Uncontrolled group had a significantly smaller left ventricular diastolic volume index (71 [59–85] vs 82 [66–109] /ml/m2, p=0.02), left ventricular systolic volume index (50 [39–59] vs 59 [42–80] / ml/m2, p=0.04), stroke volume index (22 [18–26] vs 26 [20–32] /ml/m2, p=0.02), left atrial volume index (47 [40–64] vs 59 [45–71] /ml/m2, p=0.02), and more hemodialysis (12 vs 3%, p=0.04) than Controlled group. However, the discrimination ability of these parameters for identifying Uncontrolled group was modest (Figure). Conclusion In rural Japan, possible candidates for ivabradine may be rare, so daily attention should be paid. Patients with reduced ejection fraction, small left ventricle, and hemodialysis may be the possible targets for this therapy. FUNDunding Acknowledgement Type of funding sources: None.

Use of passive leg rise as an add-on to dobutamine in patients with paradoxical low-flow, low-gradient aortic stenosis

Background Dobutamine has been proposed for the assessment of low-flow, low-gradient aortic stenosis (LFLGAS). However, in 1/3 of patients, no increase in stroke volume index can be achieved by Dobutamine, thus hampering its diagnostic value. This study evaluated the manoeuvre of cardiac preload augmentation by passive leg rise (PLR) alone or on top of Dobutamine to increase stroke volume index (SVI) in patients with LFLGAS, particularly in paradoxical LFLGAS. Methods We examined 50 patients with LFLGAS. Patients were assigned to the paradoxical LFLGAS (Paradox) group if left ventricular ejection fraction (LVEF) was ≥50% (n=29) and to the LFLGAS with low ejection fraction (LEF) group if LVEF was &lt;50% (n=21). A modified Dobutamine stress echocardiography was performed in all patients with the following 4 steps: Rest, PLR alone, maximal Dobutamine infusion rate alone (Dmax) and Dobutamine plus PLR (Dmax + PLR). Three SVI measurement methods were used: first the left ventricular outflow tract velocity time integral (LVOT VTI) method, second the 2D Simpson's method, and third the 3D method. The corresponding aortic valve area (AVA) was obtained by the continuity equation. The increase of those values compared to measurements at rest was calculated and compared between the 3 stress steps. Results In the paradoxical LFLGAS group, delta SVI with Dmax assessed by both Simpson's (depicted in the figures) and 3D method was lowest compared to PLR and Dmax + PLR. PLR alone yielded an equally high delta SVI as Dmax + PLR in Simpson's and 3D, and was at least as high as Dmax across all methods. Dobutamine alone yielded the lowest delta transaortic aortic valve VTI. The highest delta aortic valve area resulted for Dmax + PLR. In the LEF group, the three stress steps yielded an equally high delta SVI with Simpson's method. Dmax never yielded a higher delta SVI than PLR alone. The yielded delta SVI was the highest for Dmax + PLR for both LVOT VTI and 3d method, although the difference was overall not as strong as in the Paradox group. Conclusions In patients with paradoxical LFLGAS, Dobutamine alone is inadequate for testing the potential of aortic valve opening augmentation. Instead, PLR alone or the addition of PLR plus Dobutamine should be used for that purpose. In low LVEF, adding PLR to Dobutamine also seems useful although its diagnostic added value is less evident than in the Paradox group. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Gottfried und Julia Bangerter-Rhyner-Foundation Paradox group Low ejection fraction group

TAVR in patients with low-flow low-gradient aortic stenosis – outcome data after three years from one large centre

Background The outcome of patients with low-flow low-gradient (LFLG) aortic stenosis after transcatheter aortic valve replacement (TAVR) is not well evaluated. Long-term clinical success is thought to be less pronounced in LFLG patients compared to patients with high gradient (HG) aortic stenosis. Purpose The purpose of this study was to characterise different LFLG groups and determine their outcome after TAVR. We hypothesised that there would be relevant differences in baseline characteristics and patient survival after TAVR. Methods All patients undergoing TAVR for severe aortic stenosis at our centre between 2013 and 2019 were included in the study. Patients have been split into groups according preinterventional echocardiography data according to mean pressure gradient (dPmean), ejection fraction (EF), and stroke volume index (SVi). Patients with a dPmean &lt;40 mmHg and SVi ≤35 ml/m2 were subdivided into classical low-flow low-gradient (cLFLG, EF &lt;50%) and paradoxical low-flow (pLFLG, EF ≥50%). Patients with previous aortic valve replacement or severe aortic regurgitation were excluded from the analysis. Results 1,772 patients were analysed (mean follow-up 2.2 years, median age 81.7 [77.5–85.7] years) and split into groups: HG, 953 patients (54.3%), cLFLG, 446 patients (25.2%), and pLFLG 373 patients (21.1%). Baseline characteristics showed significant differences (p&lt;0.01), among others, in sex (male sex, HG 46.1% vs. cLFLG 69.5% vs. pLFLG 44.5%), rate of atrial fibrillation (HG 20.3% vs. cLFLG 36.3% vs. pLFLG 41.6%), coronary artery disease (HG 56.2% vs. cLFLG 73.5% vs. pLFLG 63.4%), and grade 3 or 4 mitral regurgitation (HG 2.2% vs. cLFLG 5.5% vs. pLFLG 6.8%). Accordingly, Society of Thoracic Surgeons (STS) Scores differed significantly: HG, 3.0 [2.0–5.0], cLFLG, 5.0 [3.0–7.3] pLFLG, 3.9 [2.2–6.0] (p&lt;0.01). Rates of periprocedural complications including death, device failure, pericardial effusion, stroke or myocardial infarction were comparable between groups. Mortality rate (figure 1) was highest for cLFLG patients (43.4% [95% confidence interval, 37.3–48.6%]) compared to HG (25.1% [21.6–28.5%]) or pLFLG (32.9% [26.9–38.4%]), Log-rank test, &lt;0.001. Corresponding hazard ratios were 2.1 [1.7–2.6] (p&lt;0.001) for cLFLG and 1.5 [1.2–2.0] (p&lt;0.001) for pLFLG. Similar results were obtained when adjusting to STS score (figure 2). Conclusion In this all-comer analysis, almost half of the patients belong toLFLG groups with considerable differences in patient characteristics. While equally safe during the procedure, patients with LFLG aortic stenosis show increased 3-year mortality rates compared to patients with HG aortic stenosis. Further studies evaluating this are needed. FUNDunding Acknowledgement Type of funding sources: None. Figure 1. 3-year mortality Figure 2. STS score-adjusted mortality

Association of smoking with indicators of the structure and function of left ventricle of the heart in middle-aged men

Aim. Evaluation of the association of smoking (status, intensity and duration) with indicators of the structure and function of the left ventricle of the heart in a sample of middle-aged men.Material and methods. This study is part of a 32-year prospective cohort observation of men from childhood (11-12 years). 301 (30.0%) representatives of the original population sample aged 41-44 years were included in the study. The examination included a survey on intensity of smoking, anthropometry, measuring blood pressure, pulse rate, echocardiography, and blood lipid analysis.Results. 301 men aged 41-44 included 92 (30.6%) men who had never smoked, 73 (24.3%) men smoked in the past and 136 (45.2%) men currently smoke. 75% of current smokers started smoking before age 19, of which 32.3% started smoking before age 15. The duration of smoking cessation among former smokers was 14.4 (12.5; 16.2) years. The average duration of smoking [average (95% confidence interval)] among former smokers was 14.4 (12.5; 16.2), for current smokers – 25.3 (24.6; 26.0) years. Current smoking was statistically significantly associated with higher mean values of the left ventricular myocardium mass (LVMM), the left ventricular myocardial mass index (LVMMI), the end-systolic and end-diastolic interventricular septum thickness (IVSTs/IVSTd), the end-systolic left ventricular posterior wall thickness (LVPWs), and the intensity and duration of current smoking were associated with higher values of the relative wall thickness of the left ventricle, the end-diastolic interventricular septum thickness, the end-systolic interventricular septum thickness, and with low values of the left ventricular stroke volume index (LV SVI). Multiple regression analysis showed that current smoking has an independent effect on the left ventricular myocardium mass, the left ventricular myocardial mass index and the end-diastolic interventricular septum thickness, and the duration and intensity of smoking has an effect on the index of the left ventricular stroke volume index.Conclusion. Current smoking, duration and intensity in middle-aged men is associated with unfavorable changes in indicators of the structure and function of the left ventricle of the heart. Efforts for primary prevention of smoking should begin as early as childhood and continue into adolescence and young adulthood.

Changes in Cardiac Index Induced by Unilateral Passive Leg Raising: a Novel Way for Assessing Fluid Responsiveness

Background: To evaluate the fluid responsiveness of patients, we examined the change in cardiac index (CI) during a unilateral passive leg raising (PLR) test using the ProAQT/Pulsioflex. In addition, we compared the change of CI triggered by bilateral PLR test and unilateral PLR test, and the ability to estimate volume responsiveness in patients.Methods: This was a prospective, observational study, and we enrolled 40 individuals thought of volume expansion. The data of cardiac index, stroke variation in volume, stroke volume index, along with variation in pulse pressure were obtained with ProAQT/Pulsioflex at a semi-recumbent position, during unilateral PLR, bilateral PLR, as well as after expansion of volume (500 ml saline over 15 min). If CI improved more than 15% to the expansion of volume, patients were defined as responders.Results: We excluded three patients. We found that a unilateral PLR-triggered CI increment ≥7.455% forecasted a fluid-triggered CI increment ≥15% with 77.27% sensitivity and 83.33% specificity. Meanwhile, bilateral PLR-triggered increases in CI ≥9.8% forecasted a fluid-triggered CI increment ≥15% with 95.45% sensitivity and 77.78% specificity. The area under the ROC curves constructed for unilateral and bilateral PLR-triggered changes in CI was not significantly different (p=0.1544).Conclusions: The change of CI induced by unilateral PLR may estimate volume responsiveness in patients.Trial registration: Unilateral passive leg raising test to assess patient volume responsiveness: Single-Center Observational Clinical Study, ChiCTR2100046762. Registered 28 May 2021, https://www.chictr.org.cn/edit.aspx?pid=127104&htm=4

Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial

Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve –25.6 (95% confidence intervals –31.4 to –15.9) /minute; P <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e′ ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.