Mitral E-wave Deceleration Time Research Articles

Machine learning based risk stratification of patients undergoing ventricular tachycardia ablation

Abstract Background Monomorphic ventricular tachycardia (VT) is a potentially life-threatening condition. Although radiofrequency catheter ablation represents an effective treatment method for many of these patients, significant variability is observed in postprocedural mortality, which is attributable to multiple factors, including the high burden of comorbidities. Therefore, there is a great demand for an accurate risk stratification system. Purpose We sought to implement a machine learning pipeline to predict 1-year all-cause mortality in patients undergoing VT ablation. Methods For 265 consecutive patients who underwent VT ablation at our center, we retrospectively collected demographics, medical history, cardiovascular risk factors, laboratory results, echocardiographic measurements, and VT ablation-related parameters. To predict 1-year all-cause mortality based on these features, several supervised machine learning models were trained and evaluated using 5-fold cross-validation. We applied a recursive elimination technique to identify the optimal subset of input features. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was calculated to quantify the models' performance. We also identified the most important predictors of mortality using Shapley values. As the final step, we used topological data analysis to discern and visualize patient subgroups with different mortality risk. Results 57 (22%) patients died during the 1-year follow-up period. In predicting all-cause mortality, the best performance was achieved by a random forest model utilizing 18 input features [AUC: 0.73 (95% CI: 0.68–0.78)]. This model significantly outperformed other previously published risk scores such as the I-VT [AUC: 0.63 (95% CI: 0.55–0.70), p<0.001 vs. random forest] or the PAINESD [AUC: 0.63 (95% CI: 0.55–0.71), p=0.009 vs. random forest]. The most important predictors of mortality were mitral E-wave deceleration time, cardiac resynchronization therapy, age, electrical storm, and hemoglobin concentration. In the topological network created based on the 18 input features of the best-performing random forest model, we could identify five patient subsets with different clinical characteristics and 1-year mortality rates (Figure 1). Conclusions Our machine learning model could efficiently predict 1-year all-cause mortality in patients undergoing VT ablation. Thus, it could facilitate the prompt identification of high-risk patients and the personalization of treatment and follow-up strategies, ultimately leading to improved outcomes. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Program, as part of the National Research, Development and Innovation Fund of HungaryThematic Excellence Programme of the Ministry for Innovation and Technology in Hungary

Left ventricular diastolic function in patients with breast cancer under chemotherapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Chemotherapy, in particular anthracyclines (A) and trastuzumab (T), have improved disease-free survival and overall prognosis in patients with breast cancer (BC). The use of these two different types of agents may increase myocardial injury and cancer therapy-related cardiac dysfunction (CTRCD). CTRCD is defined as a reduction of left ventricular ejection fraction (LVEF) >10% to a value <50% or as a relative reduction of global longitudinal strain (GLS) >15%. However, the role of diastolic dysfunction has been insufficiently researched. Purpose We sought to evaluate the impact of cardiotoxic treatments on left ventricular diastolic function. Methods Retrospective study of patients with first non-metastatic BC treated with A and/or T between Jan 2017 and Dec 2018 who underwent a comprehensive echocardiographic examination before, during, and after chemotherapy. We evaluated parameters of diastolic function derived from pulsed wave doppler interrogation of the mitral valve inflow (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue doppler (E/E’ ratio). Results We included 128 patients, all female with median age of 54±11 years-old, treated with A (78; 60.9%), T (14; 10.9%) or A followed by T (36; 28.1%). At the end of A therapy, E/A ratio (p=0,056), EDT (p=0,156) and E/E’ ratio (p=0,319) and left atrial volume index (LAVI) (p=0,056) did not show significant changes. At 2 years of follow-up, these parameters did not differ compared to baseline. During T therapy, diastolic parameters did not differ from baseline. At the end of T therapy (with or without A), E/E’ ratio had a statistically significant increase (8,61±2,61 vs 9,70±3,59, p<0,05) but no changes in EDT (p=0,461) or E/A ratio (p=0,464) occurred. At 2 years of follow-up, EDT had a statistically significant increase (204,90±44,24 vs 229,10±58,53, p<0,05) but no changes in E/A ratio (p=0,476) or E/E’ ratio (p=0,499) occurred. Conclusion In our sample of women with BC who underwent chemotherapy, early significant changes in diastolic parameters did not occur. One parameter of diastolic dysfunction was changed at 2 years of follow-up. In this study, BC chemotherapy has a very modest impact on LV diastolic function. Randomized studies on larger population are required. Other parameters should be considered to determine the diagnostic and prognostic role of LV diastolic function in CTRCD.

Left ventricular diastolic function in patients with breast cancer treated with anthracycline-based chemotherapy

Abstract Background Despite major progress in novel breast cancer therapeutic regimens, anthracycline-based chemotherapy (ANT) remains among the most effective therapies. Cardiotoxicity, one of the most severe adverse events of ANT, has been defined as a reduction in left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS). However, the role of early diastolic dysfunction has been insufficiently researched. We aimed to determine if diastolic dysfunction could early diagnose and predict ANT cardiotoxicity. Methods Studies that reported on echocardiographic parameters of diastolic function before and at the end of ANT in breast cancer patients without cardiac disease were included. We evaluated parameter derived from pulsed wave Doppler interrogation of the mitral valve inflow (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (E') and E/E' ratio). Results A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT (OR 2.34, 95% CI [1.49, 3.68], p<0.001), while EDT was not significantly influenced (OR 0.74, 95% CI [0.50, 1.08], p=0.121). Tissue Doppler velocity of the mitral ring E' and the LV filling pressure analysed through E/E' ratio did not show significant changes after ANT (OR 2.32, 95% CI [0.94, 5.72], p=0.068, and OR 0.79, 95% CI [0.56, 1.12], p=0.197, respectively). A modest reduction in LVEF and global longitudinal strain (GLS) was observed at the end of the ANT therapy with a difference in means of 3.77% and −1.08%, respectively. Patients receiving ANT doses over 400 mg/m2 doxorubicin or epirubicin therapeutic equivalent doses showed a significant change in E/A and E' after the therapy. Cardioprotective therapy like carvedilol, nebivolol and spironolactone did not have a significant impact on the parameter of diastolic function. Conclusion ANT has a modest early impact on LV diastolic function in patients with breast cancer without cardiac disease and cannot be validated as an early diagnostic or prognostic tool of ANT-induced cardiotoxicity. Randomized studies on larger population, using new parameter e.g. left atrial function parameter and multimodality imaging are required. Funding Acknowledgement Type of funding sources: None.

Left Ventricular Diastolic Function Following Anthracycline-Based Chemotherapy in Patients with Breast Cancer without Previous Cardiac Disease-A Meta-Analysis.

Background: Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognised that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterisation. Methods: Studies reporting on echocardiographic diastolic function parameters before and after ANT in breast cancer patients without cardiac disease were included. We evaluated pulsed wave (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e′) and E/e′ ratio) echocardiographic parameters. Results: A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT while EDT was not influenced by ANT. Additionally, e’ and E/e’ ratio showed no significant change after ANT. A modest reduction in LV ejection fraction and global longitudinal strain was observed at the end of ANT therapy. Conclusions: ANT had a modest early impact on E/A ratio, without changing EDT, e’, or E/e’ in patients with breast cancer without cardiac disease. Randomised studies on larger populations, using new parameters are required to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity.

Evaluation of Ventricular Diastolic Function in Patients With Fibromyalgia Syndrome.

This study aims to compare the diastolic functions between fibromyalgia (FM) patients and control subjects by using transthoracic echocardiography. This case-control and cross-sectional study included 34 female FM patients (mean age 43.6±8.2 years; range 28 to 57 years), who were diagnosed by The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia and defined as the FM group. A control group was defined consisting of 30 healthy females (mean age 41.2±9.1 years; range 22 to 54 years). Echocardiography findings of the groups were compared. The body mass index and mean disease duration of the FM group were 25.37±2.71 kg/m2 and 12.24 months, respectively. The body mass index of the control group was 25.58±1.49 kg/m2. There was no significant difference between the groups in terms of age and body mass index. Isovolumetric relaxation time and mitral E-wave deceleration time values were significantly higher in the FM group than in the control group (p=0.047, p=0.003, respectively). Isovolumetric relaxation time and mitral valve deceleration time are significantly prolonged in FM patients compared with healthy subjects. Female patients with FM seem to be under risk of impaired relaxation and diastolic function of the left ventricle.

Echocardiographic Left Ventricular Reverse Remodeling After 18 Months of Antihypertensive Treatment in Stage I Hypertension. Results From the Prever-Treatment Study.

Antihypertensive treatment improves echocardiographic parameters of hypertensive target organ damage in stage II hypertension, but less is known about the effects in stage I hypertension. In a cohort study nested in the randomized double-blind trial PREVER-treatment, 2-dimensional echocardiograms were performed in 110 individuals, aged 54.8 ± 7.9 years-old, with stage I hypertension at baseline and after 18 months of treatment with chlorthalidone/amiloride or losartan. At baseline, 66 (60%) participants had concentric remodeling. After antihypertensive treatment, systolic (SBP) and diastolic blood pressure (BP) were reduced from 141/90 to 130/83 mm Hg (P = 0.009). There was a significant reduction in left ventricular (LV) mass (LVM) index (82.7 ± 17.1 to 79.2 ± 17.5 g/m2; P = 0.005) and relative wall thickness (0.45 ± 0.06 to 0.42 ± 0.05; P < 0.001), increasing the proportion of participants with normal LV geometry (31% to 49%, P = 0.006). Left atrial (LA) volume index reduced (26.8 ± 7.3 to 24.9 ± 6.5 ml/m2; P = 0.001), and mitral E-wave deceleration time increased (230 ± 46 to 247 ± 67 ms; P = 0.005), but there was no change in other parameters of diastolic function. LVM reduction was significantly higher in the 2 higher tertiles of SBP reduction compared to the lower tertile. Treatment of patients with stage I hypertension for 18 months promotes favorable effects in the LA and LV remodeling. This improvement in cardiac end-organ damage might be associated with reduction of long term clinical consequences of hypertensive cardiomyopathy, particularly heart failure with preserved ejection fraction.

Effect of ultra-endurance exercise on left ventricular performance and plasma cytokines in healthy trained men.

The purpose of this study was to investigate the effect of ultra-endurance exercise on left ventricular (LV) performance and plasma concentration of interleukin (IL)-6, IL-10, IL-18 and tumour necrosis factor alpha (TNF-α) as well as to examine the relationships between exercise-induced changes in plasma cytokines and those in echocardiographic indices of LV function in ultra-marathon runners. Nine healthy trained men (mean age 30±1.0 years) participated in a 100-km ultra-marathon. Heart rate, blood pressure, ejection fraction (EF), fractional shortening (FS), ratio of early (E) to late (A) mitral inflow peak velocities (E/A), ratio of early (E’) to late (A’) diastolic mitral annulus peak velocities (E’/A’) and E-wave deceleration time (DT) were obtained by echocardiography before, immediately after and in the 90th minute of the recovery period. Blood samples were taken before each echocardiographic evaluation. The ultra-endurance exercise caused significant increases in plasma IL-6, IL-10, IL-18 and TNF-α. Echocardiography revealed significant decreases in both E and the E/A ratio immediately after exercise, without any significant changes in EF, FS, DT or the E/E’ ratio. At the 90th minute of the recovery period, plasma TNF-α and the E/A ratio did not differ significantly from the pre-exercise values, whereas FS was significantly lower than before and immediately after exercise. The increases in plasma TNF-α correlated with changes in FS (r=0.73) and DT (r=-0.73). It is concluded that ultra-endurance exercise causes alterations in LV diastolic function. The present data suggest that TNF-α might be involved in this effect.

Effect of Antiepilepsy Drug Therapy on Ventricular Function in Children With Epilepsy: A Tissue Doppler Imaging Study

Impaired cardiac myocardial function may contribute to the risk for sudden unexpected death of a patient with epilepsy. This study aimed to investigate the effect of antiepilepsy drugs (AEDs) on cardiac function in pediatric epileptic patients using standard and tissue Doppler imaging (TDI) echocardiography. This hospital-based, prospective cross-sectional study investigated 52 epileptic children (mean age 9.3±3.1years) treated with AEDs (duration 2.4-10.0years) and 36 healthy children (mean age 9.5±4.0years). In the epilepsy group, standard echocardiography showed increased left ventricular (LV) end-diastolic and end-systolic diameters, an increased LV mass index, and preserved ejection fraction. The patients also exhibited increased mitral peak A-wave velocity and mitral E-wave deceleration time as well as a decreased mitral E/A ratio. The E/Em ratio was significantly higher in the epilepsy group (5.6±1.2) than in the control group (5.2±1.1) (p=0.016). In the epilepsy group, TDI showed an increased isovolumetric relaxation time and myocardial performance index (MPI). It also exhibited decreased early diastolic velocity (Em) and a decreased mitral annular displacement index in these patients. There were positive correlations between the LV lateral wall MPI (r=0.231), septal MPI (r=0.223), and LV mass index (p<0.05) but no correlation with the duration of AED treatment. The authors detected subclinical ventricular dysfunction associated with AEDs at a preclinical stage. They suggest that TDI can be useful for determining the short- and long-term cardiac effects of AEDs.

The ‘Echo Heart Failure Score’: an echocardiographic risk prediction score of mortality in systolic heart failure

Although many transthoracic echocardiographic (TTE) measurements have been shown to predict outcome in heart failure (HF), whether incremental risk prediction is afforded by their combination is unknown. We developed a simple echocardiographic risk score of mortality in HF patients. We performed TTE in 747 systolic HF patients followed-up for 34 ± 23 months. The Cox hazard model was used to evaluate the association between 14 TTE parameters and death. The Echo Heart Failure Score (EHFS) was derived by assigning the value of 1 to each independent predictor when present, and 0 when it was absent, and then by summing the number. The 3-year risk prediction improvement was tested by adding the EHFS to a model containing clinical predictors, and by calculating the C index and net reclassification improvement (NRI). Five baseline TTE variables (end-systolic volume index, left atrial volume index, mitral E-wave deceleration time, tricuspid annular peak systolic excursion, and pulmonary artery systolic pressure) remained independent predictors of mortality. The mortality rate (per 100 patients/year) significantly increased with EHFS ranging from 0 to 5 (EHFS = 0, 2.7%; 1, 5.2%; 2, 10.1%; 3, 13.7%, 4, 29.7%; 5, 36.9%; P < 0.0001). Patients with EHFS ≥3 had a mortality hazard ratio of 3.58 (95% confidence interval 2.74-4.78) compared with EHFS <3. Adding EHFS to the base model improved the C index (from 0.74 to 0.81, P < 0.0001), yielding a continuous NRI of 0.63 (P < 0.0001). The EHFS, an easily obtainable echo score, improved risk prediction of death over traditional prognostic factors in systolic HF patients, and it may prove useful for risk stratification.

Evaluation of Atrial Electromechanical Delay and Diastolic Functions in Patients with Hyperthyroidism

Hyperthyroidism is a well-known cause of atrial fibrillation (AF) which is associated with increased morbidity and mortality. Atrial electromechanical delay (EMD) is a significant predictor of AF. The aim of this study was to assess the atrial EMD and diastolic functions in subclinical and overt hyperthyroidism by using tissue Doppler imaging (TDI). The study population consisted of 3 groups: group I (30 healthy subjects), group II (38 patients with subclinical hyperthyroidism), and group III (25 patients with overt hyperthyroidism). Atrial electromechanical coupling was measured with TDI. Standard echocardiographic measurements and parameters of diastolic function were obtained by conventional echocardiography and TDI. Intra- and inter-atrial EMD were significantly prolonged in subclinical and overt hyperthyroidism compared with control group (P=0.03 and P<0.001 for intra-atrial EMD; P<0.001 for inter-atrial EMD). In groups II and III, mitral A velocity (P=0.005 and P=0.001) and mitral E-wave deceleration time (P<0.001 and P=0.02) were significantly increased, and mitral E/A ratio (P=0.005 and P=0.001) was significantly decreased compared with the control group. The lateral mitral Em /Am ratio in group II and group III was significantly lower than controls (P=0.001). Mitral Em /Am ratio (β=-0.32, P=0.002) and thyroid stimulating hormone (TSH) level (β=-0.27, P=0.009) were negatively and independently correlated with inter-atrial EMD. This study showed that intra- and inter-atrial electromechanical intervals were prolonged and diastolic function was impaired in both overt and subclinical hyperthyroidism. TSH level and mitral Em /Am ratio were found as independent predictors of atrial EMD.

Coronary Flow Reserve and Myocardial Performance Index in Newly Diagnosed Diabetic Patients

Patients with diabetes mellitus (DM) are at high risk of left ventricular (LV) dysfunction. A reduction of coronary flow reserve (CFR) has been demonstrated in diabetic patients without coronary artery stenosis. In this study, we investigated the association between LV myocardial diastolic and systolic functions and the CFR in newly diagnosed diabetic patients in the absence of coronary artery disease. We studied 88 patients (mean age 49±10years) with newly diagnosed DM and 40 healthy control subjects (mean age 50±9years). All subjects underwent transthoracic echocardiography. The myocardial performance index (MPI) was determined by using pulsed-wave Doppler. The CFR was calculated as the hyperemic to resting coronary diastolic peak velocities ratio. Patients with diabetes had significantly longer mitral E-wave deceleration time and higher MPI value than control group (P=0.023 and P<0.001, respectively). The mean CFR was lower in diabetic patients compared with controls (P=0.001). The MPI was significantly correlated with CFR (r=-0.371, P<0.001), LV ejection fraction (r=-0.274, P=0.018) E/A ratio (r=-0.244, P=0.024), and glycosylated hemoglobin (HbA1c) (r=0.476, P<0.001). Multivariate regression analysis showed that MPI was independently associated with CFR (β=-0.292, P<0.0001) and HbA1c level (β=0.372, P<0.0001). The MPI was independently associated with CFR in newly diagnosed diabetic patients. The decrease in CFR may cause LV systolic and diastolic dysfunction in asymptomatic diabetic patients.

Role of Left Ventricular Dyssynchrony in Predicting Remodeling after ST Elevation Myocardial Infarction

Intraventricular dyssynchrony is associated with worsening systolic function, adverse remodeling, and clinical events. The aim of this study is to investigate whether intraventricular dyssynchrony assessed by tissue Doppler imaging (TDI) can predict left ventricular (LV) remodeling after first ST segment elevation myocardial infarction (STEMI) treated successfully with primary percutaneous coronary intervention (pPCI). Fifty-two consecutive patients who presented with first acute STEMI were included in the study. All patients underwent successful pPCI. Standard echocardiography was performed within 48 hours of admission. LV dyssynchrony was assessed by color-coded TDI. Dyssynchrony (Ts-diff) was calculated by maximal temporal difference between time to peak systolic velocities (Ts) of six basal segments. Echocardiographic examination was repeated after 6 months to reassess LV volumes. LV remodeling was defined as >15% increase in LV end-systolic volume index (LVESVI) after 6 months. Eleven patients (23%) developed LV remodeling. Baseline dyssynchrony was found to be correlated with percent change in LVESVI and LV end-diastolic volume index (LVEDVI) after 6 months. Ts-diff, creatine kinase-MB and mitral inflow E-wave deceleration time (DT) were the independent predictors of remodeling after STEMI in multivariate logistic regression analysis. Receiver operating characteristic curve analysis showed that Ts-diff >56 msec had 72.7% sensitivity and 83.8% specificity for predicting remodeling. LV dyssynchrony is a strong predictor of LV remodeling after acute myocardial infarction (AMI). It could be useful in risk stratification of patients after AMI.

Echocardiographic Variables After Left Ventricular Assist Device Implantation Associated With Adverse Outcome

Background— Operative mortality after left ventricular assist device (LVAD) implantation is heavily influenced by patient selection and the technical difficulty of surgery. However, how we treat our patients and LVAD setting may affect the patient outcome beyond this period. We postulated that the presence of echocardiographic variables 1 month after surgery suggesting appropriate degree of LV unloading and an adequate forward flow would be important in determining clinical outcomes after the initial successful LVAD implantation. Methods and Results— We retrospectively analyzed various variables in echocardiographic examinations performed 30 days after LVAD implant in 76 consecutive patients receiving continuous flow device for their association with a compound end point (90-day mortality, readmission for heart failure, or New York Heart Association class III or higher at the end of the 90-day period). The echocardiographic associations examined included estimated LVAD flow, with and without native LV contribution, interventricular septal position, the status of aortic valve opening, an estimated left atrial pressure (ELAP), the mitral flow E-wave deceleration time, and the ratio of deceleration time to E-wave velocity (mitral deceleration index [MDI]). Four patients died during the 30- to 90-day period, 6 patients were readmitted for heart failure, and 25 patients were considered to have New York Heart Association class III or higher at the end of the 90-day period. Variables associated with adverse outcome included increased ELAP (odds ratio, 1.30 [1.16–1.48]; P &lt;0.0001), MDI &lt;2 ms/[cm/s] (odds ratio, 4.4 implantation [1.22–18]; P =0.02) and decreased tricuspid lateral annulus velocity (odds ratio, 0.70 implantation [0.48–0.95]; P =0.02). A leftward deviation of interventricular septum was associated with a worse outcome (odds ratio, 3.03 implantation [1.21–13.3]; P =0.01). Conclusions— Mortality and heart failure after LVAD surgery appear to be predominantly determined by echocardiographic evidence of inefficient unloading of the left ventricle and persistence of right ventricular dysfunction. Increased estimated LA pressure and short MDI are associated with worse mid term outcome. Leftward deviation of the septum is associated with worse outcome as well.

Clinical and echocardiographic correlates of intra-atrial conduction delay

The total atrial conduction time (TACT) is an important electrophysiological parameter. We developed a new transthoracic echocardiographic tool (PA-TDI). The PA-TDI interval is a reflection of the TACT. In the present study, we evaluated the clinical and echocardiographic correlates of intra-atrial conduction delay. We studied 427 patients without class I anti-arrhythmic agents or amiodarone. All patients underwent an echocardiogram and the PA-TDI interval was measured. Patient characteristics were recorded. The mean PA-TDI was 157 ± 22 ms. Multivariate linear regression analysis revealed that atrial fibrillation (AF) in history (B = 9.7; 95%CI 5.7-13.8; P < 0.001), hypertension (B = 5.5; 95%CI 1.4-9.8; P = 0.01), clinically relevant valve disease (B = 5.7; 95%CI 0.5-10.8; P = 0.03), age (B = 5; 95%CI 3.3-6.6; P < 0.001), and body mass index (BMI; B = 2.6; 95%CI 0.3-4.9; P = 0.026) were independently associated with the PA-TDI interval. On the echocardiogram: the aortic diameter (B = 0.7; 95%CI 0.2-1.2; P = 0.009), left atrial dimension (B = 0.9; 95%CI 0.5-1.3; P < 0.001), mitral valve E-wave deceleration time (B = 0.1; 95%CI 0.1-0.1; P < 0.001), aortic incompetence (B = 13; 95%CI 3.3-22.6; P = 0.008), and mitral incompetence (B = 11; 95%CI 3.6-17.5; P < 0.003) were independently associated with the PA-TDI interval. This study is the largest to investigate the relation between the atrial conduction time, underlying heart diseases, and echocardiographic parameters. We found that the PA-TDI was independently prolonged in patients with a history of AF, hypertension, valve disease, higher age, and a higher BMI. Signs of diastolic dysfunction, valve incompetence, and enlarged atrium or aortic root on the echocardiogram were associated with a prolonged PA-TDI. This suggests that early and aggressive treatment of hypertension, diastolic dysfunction, and obesity could prevent intra-atrial conduction delay.

Physiopathologic Correlates of Intrathoracic Impedance in Chronic Heart Failure Patients

Increased plasma levels of amino-terminal fraction of brain natriuretic peptide (NT-proBNP) and alterations of diastolic filling as described by Doppler transmitral flow pattern are well-known markers of decompensated heart failure (HF). Recently, some implantable defibrillators have allowed monitoring of intrathoracic impedance, which is related to lung water content, potentially indicating HF deterioration. The aim of this study was to assess the correlation between intrathoracic impedance and NT-proBNP and echo-Doppler transmitral flow indexes. Data were collected from 111 HF patients, in six Italian centers. All patients were on optimal medical therapy. Device diagnostics, echographic data, NT-proBNP determination, and clinical status as assessed by the Heart Failure Score (HFS) were registered at baseline, at bimonthly visits, and at unscheduled examinations due to HF decompensation or device alerts. Over a median follow-up of 413 days, 955 examinations were performed. Intrathoracic impedance was significantly correlated with NT-proBNP (P = 0.013) and with mitral E-wave deceleration time (DtE) (P = 0.017), but not with HFS. At the time of confirmed alert events, NT-proBNP was significantly higher than during confirmed nonalert event examinations; DtE did not differ, whereas impedance was significantly lower. A decrease in intrathoracic impedance is inversely correlated with NT-proBNP and directly correlated with DtE. Intrathoracic impedance monitoring therefore has the physiologic basis for being a useful tool to identify early HF decompensation.

Impact of Aortic Valve Stenosis on Left Atrial Phasic Function

The aim of this study was to determine the impact of aortic stenosis (AS) on the different components of left atrial (LA) function. The study consisted of a total of 52 consecutive patients with severe AS (aortic valve area < 1 cm(2)) and 20 normal subjects matched for gender, heart rate, body surface area, and baseline systolic blood pressure. Phasic LA longitudinal function was assessed using tissue Doppler imaging. LA peak systolic (reservoir function), early diastolic (conduit function), and late diastolic (active function) strain rates were measured. During late diastole, LA peak strain (active function) was also measured. Mitral annular systolic, early diastolic (Ea), and late diastolic (Aa) velocities were also measured. Compared with controls, all strain values were significantly reduced in patients with AS. By multivariate regression analysis, mitral E-wave deceleration time (p = 0.033) and E/Ea ratio (p = 0.02, R(2) = 0.43) emerged as independently associated with LA peak systolic strain rate. Ea was the sole determinant of LA early diastolic strain rate (p < 0.0001, R(2) = 0.42), whereas LA late diastolic strain rate was independently related to aortic valve area (p = 0.031) and Aa (p = 0.022, R(2) = 0.51). In conclusion, in patients with severe AS, the 3 components of LA function are reduced. LA reservoir dysfunction is related to left ventricular filling pressures, whereas LA conduit dysfunction depends on left ventricular relaxation. Active LA dysfunction is related to the severity of AS and late left ventricular diastolic function.

Plasma N‐Terminal Protype‐B Natriuretic Peptide and Restrictive Mitral Flow to Risk‐stratify Patients with Stage B Heart Failure

The prognostic role of echocardiography is well established in patients with previous or current symptoms of heart failure (HF). Less is understood about patients with stage B HF, who have structural heart disease but no symptoms at any stage. This study investigated the role of plasma N-terminal protype-B natriuretic peptide (NT-proBNP) and Doppler-echo parameters of diastolic and systolic function for risk stratification in stage B HF patients. We investigated whether plasma NT-proBNP and Doppler-echo parameters of diastolic and systolic function have a role in risk stratification of stage B HF patients. Doppler echocardiography was performed in 155 outpatients with asymptomatic left ventricular (LV) dysfunction (ejection fraction [EF] < 50%) and comprised conventional diastolic variables, including pulsed-Doppler mitral E-wave deceleration time (EDT). Plasma NT-proBNP was assessed at the time of the echocardiogram. The prespecified end point was cardiac death or HF hospitalization or any new HF episode requiring a change in medication. Mean EF was 35% +/- 7%. Median NT-proBNP was 745 pg/mL (interquartile range [IQR], 442-1672). Patients with events at follow-up (n = 46) had higher prevalence of risk factors for developing HF. Plasma NT-proBNP, EDT, and EF were independently associated with cardiac events at multivariable analysis and receiver operating characteristic curves were used to determine the optimal prognostic cut points for each: NT-proBNP > or = 831 pg/mL, EDT < 145 msec, and EF < 37%. When used in combination, event-free survival was incrementally worse with each additional abnormality. Plasma NT-proBNP, EDT, and EF are independently useful for prognostic stratification of stage B HF patients and suggest an incremental prognostic deficit is associated with the combination of each. This study supports the complementary role of comprehensive echocardiography and natriuretic peptide assay in asymptomatic LV dysfunction.

Assessment of Atrial Electromechanical Coupling Characteristics in Patients with Ankylosing Spondylitis

The aim of this study was to evaluate atrial conduction abnormalities obtained by Doppler tissue imaging (DTI) and electrocardiogram analysis in ankylosing spondylitis (AS) patients. A total of 40 patients with AS (22 males /18 females, 37.82 +/- 10.22 years), and 42 controls (22 males/20 females, 35.74 +/- 9.98 years) were included. Systolic and diastolic left ventricular (LV) functions were measured by using conventional echocardiography and DTI. Interatrial and intraatrial electromechanical coupling (PA) intervals were measured with DTI. P-wave dispersion (PD) was calculated from the 12-lead electrocardiogram. Atrial electromechanical coupling at the left lateral mitral annulus (PA lateral) was significantly delayed in AS patients (61.65 +/- 7.81 vs 53.69 +/- 6.75 ms, P < 0.0001). Interatrial (PA lateral - PA tricuspid), intraatrial electromechanical coupling intervals (PA septum - PA tricuspid), maximum P-wave (Pmax) duration, and PD were significantly longer in AS patients (23.50 +/- 7.08 vs 14.76 +/- 5.69 ms, P < 0.0001; 5.08 +/- 5.24 vs 2.12 +/- 2.09 ms, P = 0.001; 103.85 +/- 6.10 vs 97.52 +/- 6.79 ms, P < 0.0001; and 48.65 +/- 6.17 vs 40.98 +/- 5.37 ms, P < 0.0001, respectively). Reflecting LV diastolic function mitral A-wave and E/A, mitral E-wave deceleration time (DT), Am and Em/Am were significantly different between the groups (P < 0.05). We found a significant correlation between interatrial electromechanical coupling interval with PD (r = 0.536, P < 0.01). Interatrial electromechanical coupling interval was positively correlated with DT (r = 0.422, P < 0.01) and inversely correlated with E/A (r =-0.263, P < 0.05) and Em/Am (r =-0.263, P < 0.05). This study shows that atrial electromechanical coupling intervals and PD are delayed, and LV diastolic functions are impaired in AS patients.

Effects of Rosiglitazone on Cardiac Function in CAPD Patients: A Tissue Doppler Study

Background. Insulin resistance was an independent predictor of cardiovascular mortality in uremic patients without diabetes. Rosiglitazone (ROS) improves insulin sensitivity in the liver, muscle, and adipose tissue. We prospectively investigated the effects of ROS on cardiac functions by standard (SDE) and tissue Doppler echocardiography (TDI) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods. A total of 24 CAPD patients (13 males, 11 females; mean age 42.2 ± 14.8 years) were included. Routine blood samples were examined. Left and right ventricular functions were assessed, and myocardial performance index (MPI) was calculated by SDE and TDI at baseline and after 12-month ROS therapy. Left and right atrial volumes were measured and indexed to body surface area. Results. When compared with baseline, after 12 months of ROS treatment, it was shown that early (E) and late (A) diastolic velocities of atrioventricular valves, E/A ratio, mitral E-wave deceleration time (DT), isovolumetric relaxation time (IVRT), and MPI were similar (p > 0.05). Also, no significant changes were detected in LV dimensions, LV mass index, LVEF, LA volume index, or RA volume index measured by SDE before and after ROS therapy (p > 0.05). Left and right ventricular function parameters measured by TDI including Sm, Em, Am, Em/Am ratio, E/Em ratio, and MPI were similar. Conclusion. It was found that there was no negative effect of long-term ROS therapy on cardiac functions measured by SDE and TDI in CAPD patients.

Ranolazine Shortens Repolarization in Patients with Sustained Inward Sodium Current Due to Type‐3 Long‐QT Syndrome

One form of the hereditary long-QT syndrome, LQT3-Delta KPQ, is associated with sustained inward sodium current during membrane depolarization. Ranolazine reduces late sodium channel current, and we hypothesized that ranolazine would have beneficial effects on electrical and mechanical cardiac function in LQT3 patients with the SCN5A-DeltaKPQ mutation. We assessed the effects of 8-hour intravenous ranolazine infusions (45 mg/h for 3 hours followed by 90 mg/h for 5 hours) on ventricular repolarization and myocardial relaxation in 5 LQT3 patients with the SCN5A-Delta KPQ mutation. Changes in electrocardiographic repolarization parameters from before to during ranolazine infusion were evaluated by time-matched, paired t-test analyses. Cardiac ultrasound recordings were obtained before ranolazine infusion and just before completion of the 8-hour ranolazine infusion. Ranolazine shortened QTc by 26 +/- 3 ms (P < 0.0001) in a concentration-dependent manner. At peak ranolazine infusion, there was a significant 13% shortening in left ventricular isovolumic relaxation time, a significant 25% increase in mitral E-wave velocity, and a meaningful 22% decrease in mitral E-wave deceleration time compared with the baseline. No adverse effects of ranolazine were observed in the study patients. Ranolazine at therapeutic concentrations shortened a prolonged QTc interval and improved diastolic relaxation in patients with the LQT3-Delta KPQ mutation, a genetic disorder that is known to cause an increase in late sodium current.