Measurement Of Systolic Time Intervals Research Articles

A Chest‐Conformable, Wireless Electro‐Mechanical E‐Tattoo for Measuring Multiple Cardiac Time Intervals

AbstractCardiovascular diseases are the leading cause of death globally. Noninvasive, accurate, and continuous cardiovascular monitoring can enable the preemptive detection of heart diseases and timely intervention to prevent serious cardiac complications. However, unobtrusive, ambulatory, and comprehensive cardiac monitoring is still a challenge as conventional electronics are rigid, heavy, or consume too much power for long‐term measurement. This work presents a thin (200 µm), stretchable (20%), lightweight (2.5 g), wireless, and low‐power (<3 mW) cardiac monitoring device that conforms to the human chest like a temporary tattoo sticker, correspondingly known as an e‐tattoo. This chest e‐tattoo features dual‐mode electro‐mechanical sensing—bio‐electric cardiac signals via electrocardiography and mechanical cardiac rhythm via seismocardiography. A unique peripheral synchronization strategy between the two sensors enables the measurement of systolic time intervals like the pre‐ejection period and the left ventricular ejection time with high accuracy (error = −0.44 ± 8.74 ms) while consuming very low power. The e‐tattoo is validated against clinically approved gold‐standard instruments on five human subjects. The good wearability and low power consumption of this e‐tattoo permit 24‐h continuous ambulatory monitoring.

The effect of mild dynamic exercise on the electromechanical systole of heart in non-athlete, healthy first year medical students of Bengal as a predictive biomarker of arrhythmia

Introduction and Aim: Measurement of Systolic Time Intervals (STIs) is a non-invasive and convenient way of assessing left ventricular electro-mechanical activity. In this study, we assessed effect of mild dynamic exercise on QT, QS2, QT/QS2 ratio, QS2-Index among healthy young first year students at a government medical college of West Bengal, India and compared the same among girls and boys. Materials and Methods: IX-TA-220 multichannel recorder was used to record Electrocardiogram, Phonocardiogram and Carotid pulse tracing among 180 subjects before and after 1 minute of mild exercise with Harvard's Step of 30 cm height with metronome rhythm of 120 beats per minute. Results were analyzed by Microsoft Excel and comparison of each parameter between boys and girls were done using SPSS software in two hemodynamic states. P-value <0.05 was taken as statistically significant. Results: Post exercise mean QT and QS2 shortened and their ratio QT/QS2 increased. There was a statistically significant difference between pre-exercise and post-exercise mean QT, QT/QS2 ratio, QS2 index and significant differences were observed between mean values of the boys and girls. Conclusion: With hemodynamic changes as in exercise, due to sympathetic stimulation & catecholamine release, both QT andQS2 should reduce as all the phases of systole shorten but if QT does not reduce in comparison to QS2 it may lead to arrhythmia in future. Hence QT/QS2 can be a useful pro-arrhythmic biomarker and may complement ECG and Echocardiography in borderline cases.

Contactless Measurement of Human Systolic Time Intervals Based on Doppler Cardiograms in Clinical Environment

As the most important organ of human body, heart has many measures and indicators to assess the cardiac function in clinic. Ventricular systolic time intervals (STIs) are of major relevance in providing crucial information regarding cardiovascular state. However, the existing measurement technologies are costly, complicated to operate, and also require contact sensors. Based on the human cardiovascular model and principle of Doppler cardiogram (DCG), the differential DCG (D-DCG) and quadratic D-DCG (QD-DCG) carry the aortic pressure (AP) information by which the STIs can be calculated. A 24-GHz digital dc-tuning Doppler radar sensor (DRS) has been implemented to detect the accurate DCGs. To assess the feasibility of contactless measurement of the STIs by DRS, clinical experiments and evaluations are carried out in the operation theater (OT). The preejection period (PEP) and the left ventricular ejection time (LVET) estimation results reached 95.23% and 93.12% accuracy, respectively, which indicates that the proposed method has great potential to be used for STIs estimation and could be convenient for patient home monitoring.

A narrative review of clinical applications of systolic time intervals

Systolic time interval (STI) estimation is an established noninvasive method for the quantifiable assessment of left ventricular (LV) performance in well-being and disease states; it stays valuable for clinical application and forms no burden to the subjects. This manuscript reviews the potential clinical applications and prognostic value of STI for the assessment of LV systolic function in cardiovascular disease (CVD). STIs could be obtained by several noninvasive imaging modalities such as transthoracic echocardiography, tissue Doppler imaging M-mode echocardiography, conventional echocardiography, and so on. In view of that, a literature review for studies reporting the clinical applications of STI in assessing LV systolic function among CVD patients was carried out using PubMed search. Accordingly, the current review describes how STI can be measured; reliability of cardiac time interval measurement in patients with CVD and its role in a clinical setting. With the advent of modern techniques, STI could be easily measured in a clinical setting. Likewise, STI parameter, particularly preejection period and LV ejection time ratio (PEP/LVET), has got the highest degree of correlation with LV ejection fraction (LVEF) in assessing LV performance. Furthermore, reproducibility of systolic ejection time (SET) achieved by the TDI M-mode method is outstanding and better when compared with the reproducibility of SET obtained by the conventional pulsed Doppler method. Furthermore, prolonged SET is independently related with enhanced outcomes among heart failure with reduced EF (HFrEF, i.e., EF ≤40%) but not HF with preserved EF (HFpEF, i.e., EF >40%) patients, indicating that stabilizing SET would be helpful in the case of systolic dysfunction. Clinically, tissue Doppler-derived time intervals could be beneficial to analyze abnormal cases in comparison with other invasive and noninvasive methods of ventricular function examination. Furthermore, phonoelectrocardiography-derived STI parameters, particularly electromechanical activation time-to-LVET ratio, may have a significant role in the diagnostic approach of heart failure (HF) in patients with undifferentiated dyspnea. In addition, in HF patients, PEP/LVET of >0.43 helps to detect LVEF <35% by pulsed Doppler echocardiography. Moreover, LVET continues to be an independent predictor of incident HF and provides incremental prognostic value on the future HF risk and death but not myocardial infarction. In conclusion, STI measurement could be useful, particularly in identifying LVEF <35% in the case of refractory HF patients. This could be beneficial in the selection of patients requiring cardiac resynchronization, specifically when accurate LVEF evaluation by echocardiography proves challenging in atrial fibrillation or if the evaluation is done by a trainee echocardiographer. Furthermore, the cardiac time intervals including SET can be acquired irrespective of rhythm. Good image quality is required for the assessment of LVEF. In contrast, evaluation of SET could be useful in the case of echocardiograms with poor quality images. As a final point, the present review suggests using an echocardiographic parameter like STIs to procure additional information regarding the risk of mortality in patients with HFrEF along with LVEF measurement.

Automatic Identification of Systolic Time Intervals in Seismocardiogram.

Continuous and non-invasive monitoring of hemodynamic parameters through unobtrusive wearable sensors can potentially aid in early detection of cardiac abnormalities, and provides a viable solution for long-term follow-up of patients with chronic cardiovascular diseases without disrupting the daily life activities. Electrocardiogram (ECG) and siesmocardiogram (SCG) signals can be readily acquired from light-weight electrodes and accelerometers respectively, which can be employed to derive systolic time intervals (STI). For this purpose, automated and accurate annotation of the relevant peaks in these signals is required, which is challenging due to the inter-subject morphological variability and noise prone nature of SCG signal. In this paper, an approach is proposed to automatically annotate the desired peaks in SCG signal that are related to STI by utilizing the information of peak detected in the sliding template to narrow-down the search for the desired peak in actual SCG signal. Experimental validation of this approach performed in conventional/controlled supine and realistic/challenging seated conditions, containing over 5600 heart beat cycles shows good performance and robustness of the proposed approach in noisy conditions. Automated measurement of STI in wearable configuration can provide a quantified cardiac health index for long-term monitoring of patients, elderly people at risk and health-enthusiasts.

Systolic time intervals combined with Valsalva maneuver for the diagnosis of left ventricular dysfunction in COPD exacerbations.

BackgroundThe goal of this study was to determine the value of systolic time intervals and their change during Valsalva maneuver (VM) in the diagnosis of left ventricular dysfunction (LVD) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).MethodsWe included 166 patients admitted to the emergency department for AECOPD. Measurement of systolic time intervals included electromechanical activation time (EMAT), left ventricular ejection time (LVET), and EMAT/LVET ratio. These were performed at baseline and during the first strain phase of the VM using a computerized phonoelectrocardiographic method. The diagnosis of LVD was determined on the basis of clinical examination, echocardiography, and brain natriuretic peptide. The values of systolic time intervals were compared between patients with and without LVD; their diagnostic performance was assessed using the area under receiver operating characteristic (ROC) curve.ResultsPatients with LVD (n=95) had a significantly higher EMAT and lower LVET and EMAT/LVET ratio compared to patients without LVD (n=71); the area under ROC curve was 0.79, 0.88, and 0.90, respectively, for EMAT, LVET, and EMAT/LVET ratio. All baseline systolic time intervals changed significantly during VM in patients without LVD but they did not change in patients with LVD. The area under ROC curve increased to 0.84 and 0.93, respectively, for EMAT and EMAT/LVET ratio but did not change for LVET.ConclusionSimple and noninvasive measurements of systolic time intervals combined with VM could be helpful to detect or rule out LVD in patients admitted to the emergency room for COPD excacerbation. The EMAT/LVET ratio seems to have the best diagnostic value.

Beat-to-beat systolic time-interval measurement from heart sounds and ECG

Systolic time intervals are highly correlated to fundamental cardiac functions. Several studies have shown that these measurements have significant diagnostic and prognostic value in heart failure condition and are adequate for long-term patient follow-up and disease management. In this paper, we investigate the feasibility of using heart sound (HS) to accurately measure the opening and closing moments of the aortic heart valve. These moments are crucial to define the main systolic timings of the heart cycle, i.e. pre-ejection period (PEP) and left ventricular ejection time (LVET). We introduce an algorithm for automatic extraction of PEP and LVET using HS and electrocardiogram. PEP is estimated with a Bayesian approach using the signal's instantaneous amplitude and patient-specific time intervals between atrio-ventricular valve closure and aortic valve opening. As for LVET, since the aortic valve closure corresponds to the start of the S2 HS component, we base LVET estimation on the detection of the S2 onset. A comparative assessment of the main systolic time intervals is performed using synchronous signal acquisitions of the current gold standard in cardiac time-interval measurement, i.e. echocardiography, and HS. The algorithms were evaluated on a healthy population, as well as on a group of subjects with different cardiovascular diseases (CVD). In the healthy group, from a set of 942 heartbeats, the proposed algorithm achieved 7.66 ± 5.92 ms absolute PEP estimation error. For LVET, the absolute estimation error was 11.39 ± 8.98 ms. For the CVD population, 404 beats were used, leading to 11.86 ± 8.30 and 17.51 ± 17.21 ms absolute PEP and LVET errors, respectively. The results achieved in this study suggest that HS can be used to accurately estimate LVET and PEP.

Assessment of Systolic and Diastolic Function in Asymptomatic Subjects Using Ambulatory Monitoring With Acoustic Cardiography

Adequately recording diastolic heart sounds and systolic time intervals over longer periods is difficult. Thus, information on the circadian variation of these parameters in an ambulatory population is lacking. Moreover, age-related changes in the prevalence of diastolic heart sounds and measurements of systolic time intervals in an asymptomatic population have not been studied in continuous recordings. Diastolic heart sounds and systolic time intervals will have age and circadian variations that reflect known changes in cardiac function due to aging and circadian rhythms. We studied 128 asymptomatic subjects wearing an ambulatory monitor with acoustic cardiography. The recording spanned a mean duration of 14 hours, including sleep. Data were analyzed for the presence of third (S3) and fourth (S4) heart sounds and for systolic time intervals. In these asymptomatic subjects, S3 was significantly more prevalent in those age <40 years than in those age >40 years, and significantly more pronounced during sleep in the younger group. Also, S4 was significantly more prevalent in those age >40 years and significantly more pronounced during sleep in those age >40 years. In contrast, time intervals reflecting systolic function showed less circadian variation and less worsening with age. The nocturnal increase of S4 in the elderly reflects diastolic impairment-likely a result of changes in diastolic filling patterns with increasing age. An S3 after the age of 40 is a relatively uncommon finding and therefore should be a specific sign of cardiac disease. Continuous monitoring of diastolic heart sounds and systolic time intervals is possible using acoustic cardiography.

Systolic time intervals as simple echocardiographic parameters of left ventricular systolic performance: correlation with ejection fraction and longitudinal two-dimensional strain

Conventionally, the evaluation of left ventricular (LV) systolic function is based on ejection fraction assessment, which may be supplemented by other echocardiographic techniques, such as tissue Doppler imaging, 3D evaluation, and speckle tracking strains. However, these imaging modalities have a high technicity and are time-consuming, while being associated with reproducibility limitations. In this context, the usefulness of simpler measurements such as systolic time intervals (STI) by pulsed Doppler echocardiography must be emphasized. In this multicentre study, left ventricular ejection fraction (LVEF), dP/dt(max), LV stroke volume, myocardial longitudinal deformation, aortic pre-ejectional period (PEP, ms), and left ventricular ejection time (LVET, ms) were prospectively investigated and compared in 134 consecutive heart failure (HF) patients and 43 control subjects. Feasibility of STI measurements was 100%. Intra-observer reproducibility was 98% for PEP, 96% for LVET, 87% for LVEF, and 93% for global longitudinal strain (GLS). By subgroup analyses, with increasingly altered LVEF or GLS, PEP significantly increased, whereas significantly LVET decreased, resulting in a significantly increased PEP/LVET ratio (P < 0.001). In the HF patients group, a correlation between LVEF and PEP/LVET was found, with r = 0.55 (y = -0.0083x + 0.75, P < 0.001). Based on receiver operating curve analyses, the area under the curve was 0.91 for PEP/LVET > 0.43, which allowed us to detect LVEF < 35% with a sensitivity of 87%, and a specificity of 84%. STI can be easily and accurately measured in clinical practice, and may be used for detecting alterations in LV systolic function. Moreover, this method is likely to have potential applications in the management of HF patients.

Beyond auscultation--acoustic cardiography in the diagnosis and assessment of cardiac disease.

Auscultation has long been an important part of the evaluation of patients with known and suspected cardiac disease. The subsequent development of phonocardiography provided an analogue visual display that permitted a more detailed analysis of the timing and acoustical characteristics of heart sounds, murmurs, clicks and rubs. In addition, the measurement of systolic time intervals enabled a valuable non-invasive assessment of left ventricular function. Acoustic cardiography, a much more recently developed technology, has enabled the simultaneous acquisition of ECG and cardiac acoustical data. This user-friendly and cost-effective technology permits acquisition of detailed information regarding systolic and diastolic left ventricular function and provides both a computerized interpretation and a visual display of the findings. Its clinical applications include the evaluation of patients with suspected heart failure, ischaemia and cardiac arrhythmias and the optimization of cardiovascular drug and device therapies. It can also be used in a wide variety of ambulatory and inpatient monitoring applications.

Beyond auscultation--acoustic cardiography in the diagnosis and assessment of cardiac disease.

Auscultation has long been an important part of the evaluation of patients with known and suspected cardiac disease. The subsequent development of phonocardiography provided an analogue visual display that permitted a more detailed analysis of the timing and acoustical characteristics of heart sounds, murmurs, clicks and rubs. In addition, the measurement of systolic time intervals enabled a valuable non-invasive assessment of left ventricular function. Acoustic cardiography, a much more recently developed technology, has enabled the simultaneous acquisition of ECG and cardiac acoustical data. This user-friendly and cost-effective technology permits acquisition of detailed information regarding systolic and diastolic left ventricular function and provides both a computerized interpretation and a visual display of the findings. Its clinical applications include the evaluation of patients with suspected heart failure, ischaemia and cardiac arrhythmias and the optimization of cardiovascular drug and device therapies. It can also be used in a wide variety of ambulatory and inpatient monitoring applications.

Hemodynamic Correlates of the Third Heart Sound and Systolic Time Intervals

Bedside diagnostic tools remain important in the care of patients with heart failure. Over the past two centuries, cardiac auscultation and phonocardiography have been essential in understanding cardiac pathophysiology and caring for patients with heart disease. Diastolic heart sounds (S3 and S4) and systolic time intervals have been particularly useful in this regard. Unfortunately, auscultation skills have declined considerably, and systolic time intervals have traditionally required carotid pulse tracings. Newer technology allows the automated detection of heart sounds and measurement of systolic time intervals in a simple, inexpensive, noninvasive system. Using the newer system, the authors present data on the hemodynamic correlates of the S3 and abnormal systolic time intervals. These data serve as the foundation for using the system to better understand the test characteristics and pathophysiology of the S3 and systolic time intervals, and help to define their use in improving the bedside diagnosis and management of patients with heart failure.

Hemodynamic Correlates of the Third Heart Sound and Systolic Time Intervals

Bedside diagnostic tools remain important in the care of patients with heart failure. Over the past two centuries, cardiac auscultation and phonocardiography have been essential in understanding cardiac pathophysiology and caring for patients with heart disease. Diastolic heart sounds (S3 and S4) and systolic time intervals have been particularly useful in this regard. Unfortunately, auscultation skills have declined considerably, and systolic time intervals have traditionally required carotid pulse tracings. Newer technology allows the automated detection of heart sounds and measurement of systolic time intervals in a simple, inexpensive, noninvasive system. Using the newer system, the authors present data on the hemodynamic correlates of the S3 and abnormal systolic time intervals. These data serve as the foundation for using the system to better understand the test characteristics and pathophysiology of the S3 and systolic time intervals, and help to define their use in improving the bedside diagnosis and management of patients with heart failure.

Systolic time intervals assessed by 2‐D echocardiography and spectral Doppler in the horse

ABSTRACTIn the present study, the ‘acoustic windows’ for the measurement of the left ventricular systolic time intervals is studied by means of 2‐D echocardiography and cardiac Doppler ultrasonography, and the normal values in the horse (n = 112) are determined. The left ventricular isovolumetric contraction time, the pre‐ejection period (PEP), as well as the left ventricular ejection time (LVET) have been measured, and the values of the left ventricular total electromechanical systole (LVTES) and the PEP‐to‐LVET ratio have been calculated. It has been established that the most suitable window for the measurement of the aforementioned indices in 2‐D echocardiography is the right parasternal window in a view in short axis at the level of the cardiac base to measure the aortogram. In Doppler ultrasonography, the preferred window is the left parasternal using the five chambers apical view. The following values have been acquired: PEP = 0.071 ± 0.01 s; LVET = 0.532 ± 0.097 s; LVTES = 0.6 ± 0.1 s and PEP‐to‐LVET = 0.138 ± 0.025 measured by 2‐D echocardiography and PEP = 0.068 ± 0.009 s; LVET = 0.527 ± 0.076 s; LVTES = 0.598 ± 0.098 s and PEP‐to‐LVET = 0.131 ± 0.01 measured by Doppler ultrasonography.

Measurements of systolic time intervals using a transoesophageal pulsed echo-Doppler

Measurement of systolic time intervals (STI), an index of left ventricular (LV) systolic function, is usually labour intensive and requires considerable expertise to perform accurately. We have evaluated the accuracy of an automated, continuous and non-invasive STI measurement technique using a descending aortic blood velocity Doppler signal obtained using a transoesophageal echo-Doppler system (TEDS) and an ECG signal. STI were measured in adult pigs using a transoesophageal probe (4 x 4 mm pulsed wave Doppler transducer, 5-MHz frequency and a 3 x 3 mm echo transducer, 10-MHz frequency) associated with an ECG recorder. Measurements were performed at baseline and after injection of esmolol and dobutamine. TEDS data were compared with those obtained by one-line recordings of the electrocardiogram and the central aortic arterial pressure wave. Similar mean values were observed for pre-ejection period (PEPI), LV ejection time (LVET) and PEP/LVET with the two methods. Agreement between the methods (Bland and Altman's test) was excellent with 95% confidence intervals for PEP, LVET and PEP/LVET of -7.17 to +1.37 ms, -12.64 to +0.24 ms and -0.033 to +0.028, respectively. We conclude that the combination of descending aorta blood velocity Doppler and ECG signal is an alternative technique for non-invasive and objective measurement of STI, allowing continuous monitoring of LV systolic function.

Systemic NO Synthase Inhibition Blunts the Chronotropic, but Not the Inotropic Response to Isoprenaline in Man

There is evidence that nitric oxide (NO) is involved in the chronotropic, the inotropic, and the vasodilator response to β-adrenoceptor agonists. In the present study we hypothesized that inhibition of NO synthase may modulate the systemic vascular and cardiac effects of isoprenaline, a β-adrenoceptor agonist, in healthy subjects. Subjects received stepwise increasing doses of isoprenaline (0.1–0.8 μg/min) in the absence or presence of systemic NO-synthase inhibition using two intravenous doses of N-monomethyl-l-arginine (L-NMMA; dosage 1, 3.0 mg/kg over 5 min, followed by 30 μg/kg/min over 75 min; dosage 2, 6.0 mg/kg over 5 min, followed by 60 μg/kg/min over 75 min) or peripheral vasoconstriction using exogenous endothelin-1 (ET-1; 5.0 ng/kg/min for 80 min). The chronotropic (RR interval) and the inotropic (QS2c) responses were assessed by noninvasive measurement of systolic time intervals. L-NMMA alone did not influence QS2c, but did increase the RR interval (P < 0.001) and the mean arterial blood pressure (P = 0.003). L-NMMA did not attenuate the blood pressure and the QS2c responses to isoprenaline, but significantly and dose-dependently blunted the heart rate response to β-adrenoceptor stimulation (P = 0.029). ET-1 decreased the RR interval (P < 0.001) and increased the mean arterial blood pressure (P = 0.028). Our results indicate that β-adrenoceptor mediated effects on the heart rate are much more susceptible to NOS inhibition than inotropic responses. This indicates that NO has an important role in heart rate control during β-adrenoceptor stimulation.

Positive inotropic effects of the beta2-adrenoceptor agonist terbutaline in the human heart: Effects of long-term beta1-adrenoceptor antagonist treatment

Objectives. This study was conducted to determine whether activation of cardiac beta2-adrenoceptors increases contractility in humans and whether this is affected by long-term beta1-adrenoceptor antagonist treatment.Background. Coexistence of beta1- and beta2-adrenoceptors in the human heart is generally accepted. The functional importance of cardiac beta2-adrenoceptors for increases in contractility in humans, however, has not been completely established.Methods. We studied 1) the beta-adrenoceptor subtype mediating positive inotropic effects of the beta2-adrenoceptor agonist terbutaline in vitro (on right atrial and left ventricular preparations from nonfailing human hearts) and increases in contractility (by measurement of systolic time intervals) in vivo in seven healthy male volunteers; and 2) in vivo whether long-term treatment of volunteers with the beta1-adrenoceptor antagonist bisoprolol affects terbutaline-induced increases in contractility.Results. In vitro terbutaline caused a concentration-dependent increase in atrial and ventricular adenylate cyclase activity and force of contraction. Terbutaline effects were antagonized only by the beta2-adrenoceptor antagonist ICI 118,551, indicating that they were mediated by beta2-adrenoceptor stimulation. In vivo intravenous infusions of terbutaline (dose range 25 to 300 ng/kg body weight per min for 15 min) dose dependently increased heart rate and shortened the pre-ejection period and heart rate-corrected electromechanical systole (QS2) time. These effects are mediated predominantly by beta2-adrenoceptor stimulation because they were only marginally affected by the beta1-adrenoceptor antagonist bisoprolol (1 × 10 mg orally), either given 2 h before infusion or long term for 3 weeks.Conclusions. Stimulation of cardiac beta2-adrenoceptors in humans causes not only in vitro but also in vivo positve inotropic effects. Long-term beta1-adrenoceptor antagonist treatment does not considerably affect beta2-adrenoceptor-mediated in vivo increases in contractility. Thus, it may be possible to treat patients with chronic heart failure and long-term beta1-adrenoceptor antagonist therapy with beta2-adrenoceptor agonists if immediate inotropic support is needed.

Noninvasive Measurement of Peripheral Pressure Pulse Compliance and Systolic Time Intervals

Systolic time intervals provide a basis for the indirect determination of total electromechanical systole and offer a physiologic approach to cardiovascular assessment. In addition, examination of the pulse wave contour changes with advancing age and hypertension suggests that these data may be useful in assessing the vascular compliance and peripheral resistance of a subject. In this report, we explore the use of noninvasively obtained peripheral systolic time intervals in normal and pathologic conditions and the automated measurement and continuous plotting of several parameters, including heart rate, pulse wave arrival time, rapid ejection time, peripheral pulse wave contour, and cutaneous pressure pulse. Although this is an empirical system whose clinical usefulness has yet to be determined, the development of peripheral systolic time intervals seems promising.

Selected Issues From an Overview on Nicorandil

Nicorandil exerts its pharmacodynamic effects through two different modes of action: increase of cyclic GMP and activation of K+ channels of smooth muscle cells. The latter mechanism could explain the lack of development of tolerance that had been demonstrated clearly in various animal experiments. Therefore, it was attempted to elucidate this mechanism in humans. In 16 healthy subjects, the acute hemodynamic effects of a single oral dose of 40 mg nicorandil were compared with those of a single sublingual dose of 0.8 mg nitroglycerin. Thereafter, the subjects were treated with 30 mg isosorbide-5-mononitrate (IS-5-MN) slow release t.i.d. for 7 days to induce nitrate tolerance. Two hours after the last dose of IS-5-MN, hemodynamic measurements were repeated before and after administration of nicorandil and nitroglycerin, respectively. Recordings obtained from impedance cardiography and finger plethysmography as well as measurements of systolic time intervals provided evidence that nicorandil in the state of IS-5-MN tolerance continued to exert hemodynamic effects similar to those exerted after the first dose. The hemodynamic actions of nitroglycerin were no longer observed after chronic treatment with IS-5-MN. The duration of action of nicorandil was investigated in 22 patients with coronary artery disease (CAD). After a 2-week run-in period on placebo, patients had to perform a symptom-limited bicycle exercise tolerance test (ETT) on two separate days in which the reproducible anginal threshold had to be proven. After qualification, patients were allocated randomly to receive double-blind 10 or 20 mg nicorandil b.i.d. for 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiographic evaluation of pulmonary artery pressure in chronic obstructive pulmonary disease. A European multicentre study

The feasibility, reproducibility and reliability of Doppler echocardiography in evaluation of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD) were determined in a multicentre study. In 100 COPD patients with mean pulmonary artery pressure ranging from 10 to 62 mmHg at cardiac catheterization, pulmonary pressure estimation was attempted by four Doppler echocardiographic methods. These methods comprised the calculation of transtricuspid and transpulmonary pressure gradients from Doppler-detected tricuspid or pulmonary regurgitation, the evaluation of right ventricular outflow tract velocity profiles with the measurement of right ventricular systolic time intervals and the measurement of the right ventricular isovolumic relaxation time. In 98 (98%) patients at least one of the methods could be employed. A tricuspid regurgitation jet was detected in 47 (47%) patients but its quality was adequate for measurement in 30 (30%). Pulmonary regurgitation jet velocity was measured only in five cases. The standard error of estimate in testing intra- and interobserver reproducibility of Doppler systolic time intervals was less than 5%. The predictive value of right ventricular outflow tract acceleration time less than 90 ms in the identification of patients with mean pulmonary artery pressure greater than 20 mmHg was 80%. Of Doppler echocardiographic data, best correlations with mean pulmonary artery pressure were found for the transtricupid gradient (r = 0.73, SEE = 7.4 mmHg), for the right ventricular acceleration time (r = 0.65, SEE = 8 mmHg) and right ventricular isovolumic relaxation time (r = 0.61, SEE = 8.5 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)