Propionyl-L-carnitine for intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance. OBJECTIVES: The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies. SELECTION CRITERIA: Double-blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain-free walking performance (initial claudication distance - ICD) and maximal walking performance (absolute claudication distance - ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed-effect model meta-analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE. MAIN RESULTS: We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L-carnitine (1 study, 26 participants). We identified no RCTs that assessed PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo. For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company-backed studies. The overall certainty of the evidence was moderate. For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain-free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu-like symptoms did not differ greatly between PLC and placebo. For the comparison of PLC with L-carnitine, the certainty of evidence was low because this included a single, very small, cross-over study. Mean improvement in ACD was slightly greater for PLC compared to L-carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI -9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI -7.4% to 13.4%). None of the other outcomes of this review were reported in this study. AUTHORS' CONCLUSIONS: When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.

Progression of incomplete toward complete left bundle branch block: A clinical and electrocardiographic analysis.

BACKGROUND: Complete left bundle branch block (cLBBB) is associated with increased cardiovascular mortality and heart failure. On the contrary, the clinical relevance of incomplete left bundle branch block (iLBBB) is less known. This study investigated the profile and outcome of iLBBB patients and assessed the risk of progression to cLBBB. METHODS: Patients diagnosed with iLBBB between July 2013 and April 2018 were retrospectively included. Subsequently, echo- and electrocardiographic examinations at time of iLBBB diagnosis and during follow-up, as well as progression to non-strict cLBBB and strict cLBBB, were evaluated. RESULTS: The study enrolled 321 patients (33% female, age 74 ± 11 years). During the follow-up of 21 (8;34) months, 33% of iLBBB patients evolved to non-strict cLBBB and 27% to strict cLBBB. iLBBB patients who evolved to non-strict or strict cLBBB were older, had more frequently reduced left ventricular ejection fraction, and had more often QRS notching/slurring in the lateral leads and inferior leads, compared to patients without progression to cLBBB. In multivariate analysis, only QRS notching/slurring in the lateral leads was independently associated with progression to non-strict cLBBB (odds ratio 4.64, p < .001) and strict cLBBB (odds ratio 9.6, p < .001). iLBBB patients with QRS notching/slurring had a progression rate to non-strict cLBBB of 52% and 49% to strict cLBBB. CONCLUSION: Among patients with iLBBB, up to one third of the patients progress to cLBBB within a period of 2 years. The presence of QRS notching/slurring in the lateral leads during iLBBB was the strongest predictor for progression toward cLBBB.

Outcome of degenerative nonprolapse mitral regurgitation using the average pixel intensity method.

BACKGROUND: Primary mitral valve regurgitation (MR) is a comprehensive term that mostly comprises mitral valve prolapse (MVP), while other causes of degenerative MR are often not considered. We describe the echocardiographic characteristics of degenerative nonprolapse mitral regurgitation (DMR) and assess the outcome at medium-term follow-up using the novel average pixel intensity (API) method. METHODS: Of 126 patients with any nonprolapse DMR were consecutively included. MR was graded according to all guideline-recommended parameters and with the API method. MR flow dynamics in DMR were compared to MVP-MR and functional MR (FMR). RESULTS: DMR is associated with moderate-to-severe calcifications of the mitral valve apparatus, and a low event rate was observed at a mean follow-up of 27 months. The API grading method had a higher feasibility (94%) compared to proximal isovelocity surface area (PISA) (60%) method and vena contracta width (VCW) (71%) for assessing MR. The API method was predictive for events. The API method also provides insights into DMR flow dynamics: A triphasic pattern was observed with a midsystolic nadir for both API and PISA-EROA, which is similar to the dynamic flow pattern described in FMR, but distinct from holosystolic MVP-MR. Compared to FMR and MVP-MR patients, DMR is less severe and patients with DMR are generally older than MVP-MR patients. CONCLUSIONS: DMR is a distinct MR pathology and conveys a relatively low event rate. MR grading was feasible with the API method, and flow dynamics demonstrated a similar triphasic pattern compared to FMR but distinct from holosystolic MVP-MR.

Relation between electrical and mechanical dyssynchrony in patients with left bundle branch block: An electro- and vectorcardiographic study.

BACKGROUND: Current guidelines select patients for cardiac resynchronization therapy (CRT) mainly on electrocardiographic parameters like QRS duration and left bundle branch block (LBBB). However, among those LBBB patients, heterogeneity in mechanical dyssynchrony occurs and might be a reason for nonresponse to CRT. This study assesses the relation between electrocardiographic characteristics and presence of mechanical dyssynchrony among LBBB patients. METHODS: The study included patients with true LBBB (including mid-QRS notching) on standard 12-lead electrocardiograms. Left bundle branch block-induced mechanical dyssynchrony was assessed by the presence of septal flash on two-dimensional echocardiography. Previously reported electro- and vectorcardiographic dyssynchrony markers were analyzed: global QRS duration (QRSDLBBB ), left ventricular activation time (QRSDLVAT ), time to intrinsicoid deflection (QRSDID ), and vectorcardiographic QRS areas in the 3D vector loop (QRSA3D ). RESULTS: The study enrolled 545 LBBB patients. Septal flash (SF) is present in 52% of patients presenting with true LBBB. Patients with SF are more frequent female, have less ischemic heart disease and smaller left ventricular dimensions. In multivariate analysis longer QRSDLBBB , QRSDLVAT and larger QRSA3D were independently associated with SF. Of all parameters, QRSA3D has the best accuracy to predict SF, although overall accuracy remains moderate (59% sensitivity, 58% specificity). The predictive value of QRSA3D remained constant in both sexes, irrespective of ischemic heart disease, ejection fraction and even when categorizing for QRSDLBBB . CONCLUSION: In LBBB patients, large QRS areas correlate better with mechanical dyssynchrony compared to wide QRSD intervals. However, the overall accuracy to predict mechanical dyssynchrony by electrocardiographic dyssynchrony markers, even when using complex vectorcardiographic parameters, remains low.

The Pixel Variation Score: An Echocardiographic Index to Assess Temporal Variation of Mitral Regurgitant Flow.

BACKGROUND: In mitral regurgitation (MR), temporal variation of MR flow has been considered an important reason for inaccurate MR grading. Current echocardiographic methods for assessing temporal MR flow variation are complex, and their clinical relevance has not been investigated. In this study, we investigated whether assessing MR flow variation using a dimensionless index with echocardiography is feasible, clinically meaningful, and related to patient outcomes. METHODS: Consecutive patients with mitral valve prolapse (MVP, n = 244) and functional MR (FMR, n = 396) underwent comprehensive echocardiography. Mitral regurgitation severity was assessed using an integrated approach advocated by current guidelines. The MR continuous-wave Doppler envelope was divided into 3 segments of equal duration. Each segment's pixel intensity was assessed to calculate the pixel variation score (PVS). RESULTS: The PVS was lower in FMR patients than in MVP patients. Lower PVS was associated with worse MR, larger left atrial and left ventricular dimensions, lower ejection fraction, and higher pulmonary artery pressures. In MVP, PVS was significantly associated with postoperative left ventricular reverse remodeling and was able to reclassify most patients in whom single-frame measures overestimated MR severity. Finally, PVS had incremental prognostic value on top of clinical and echocardiographic predictors of outcome. CONCLUSIONS: Temporal variation in MR flow can reliably be assessed with echocardiography through analysis of the continuous-wave Doppler signal. A high PVS value may alert the echocardiographer to defer from single-frame MR grading and also suggests that the MR is probably not severe.

Color Doppler Splay in Mitral Regurgitation: Hemodynamic Correlates and Outcomes in a Clinical Cohort.

BACKGROUND: Recently, an artifactual horizontal extension of the color Doppler signal was described in patients with mitral regurgitation (MR), called color Doppler splay (CDS). This side-lobe artifact was shown to be associated with concealed and significant MR. In the present study, the authors assessed the prognostic significance of CDS and its hemodynamic correlates. METHODS: Consecutive patients with primary and secondary MR underwent comprehensive transthoracic echocardiography. Machine settings were fixed for all patients. MR severity was assessed using an integrated approach, as advocated in current international guidelines. The presence of CDS and CDS width and duration were assessed. The outcome measures included the incidence of major adverse cardiac events (a composite of cardiovascular mortality, hospitalization for decompensated heart failure, mitral valve surgery, or percutaneous mitral intervention). RESULTS: One hundred twenty-seven of 469 patients (27%) with MR demonstrated CDS. The presence of CDS was associated with worse MR, and CDS width correlated with effective regurgitant orifice area, regurgitant volume, and vena contracta width. Mitral annular or leaflet calcification was inversely associated with the presence of CDS. Patients with CDS experienced worse event-free survival. For CDS width, a cutoff of >29 mm was identified as optimal regarding outcome prediction in our cohort and termed "severe CDS." In multivariate Cox regression, the presence of severe CDS was associated with adverse outcome, independent of MR etiology or severity and other clinical and echocardiographic predictors of outcome, and provided incremental prognostic value on top of these parameters. CONCLUSIONS: In patients with MR, the presence of CDS is associated with more severe MR and worse outcomes. Severe CDS provides incremental prognostic value on top of traditional MR metrics and should alert the echocardiographer that MR severity may be underestimated.

Clinical validation of a 13-lead electrocardiogram derived from a self-applicable 3-lead recording for diagnosis of myocardial supply ischaemia and common non-ischaemic electrocardiogram abnormalities at rest.

Aims: In this study, we compare the diagnostic accuracy of a standard 12-lead electrocardiogram (ECG) with a novel 13-lead ECG derived from a self-applicable 3-lead ECG recorded with the right exploratory left foot (RELF) device. The 13th lead is a novel age and sex orthonormalized computed ST (ASO-ST) lead to increase the sensitivity for detecting ischaemia during acute coronary artery occlusion. Methods and results: A database of simultaneously recorded 12-lead ECGs and RELF recordings from 110 patients undergoing coronary angioplasty and 30 healthy subjects was used. Five cardiologists scored the learning data set and five other cardiologists scored the validation data set. In addition, the presence of non-ischaemic ECG abnormalities was compared. The accuracy for detection of myocardial supply ischaemia with the derived 12 leads was comparable with that of the standard 12-lead ECG (P = 0.126). By adding the ASO-ST lead, the accuracy increased to 77.4% [95% confidence interval (CI): 72.4-82.3; P < 0.001], which was attributed to a higher sensitivity of 81.9% (95% CI: 74.8-89.1) for the RELF 13-lead ECG compared with a sensitivity of 76.8% (95% CI: 71.9-81.7; P < 0.001) for the 12-lead ECG. There was no significant difference in the diagnosis of non-ischaemic ECG abnormalities, except for Q-waves that were more frequently detected on the standard ECG compared with the derived ECG (25.9 vs. 13.8%; P < 0.001). Conclusion: A self-applicable and easy-to-use 3-lead RELF device can compute a 12-lead ECG plus an ischaemia-specific 13th lead that is, compared with the standard 12-lead ECG, more accurate for the visual diagnosis of myocardial supply ischaemia by cardiologists.

Prognostic value of myocardial work and global longitudinal strain in patients with heart failure and functional mitral regurgitation.

In patients with heart failure and functional mitral regurgitation (FMR), the assessment of left ventricular (LV) function is important for risk stratification and decision making. As LV ejection fraction (LVEF) might not be an optimal metric for LV systolic performance in this population, alternatives such as global longitudinal strain (GLS) and global myocardial work index (GWI) have been proposed. In the present study, we investigated the prognostic value of GLS and GWI and compared these measures to other LV systolic performance parameters. A prospective and consecutive cohort of 181 patients (median age 72 years, 76% male) with LVEF < 50% and FMR underwent comprehensive echocardiographic examination including speckle tracking echocardiography and grading of FMR severity. During a median follow-up of 42 months, 72 cardiovascular (CV) events occurred. In univariate analysis, LVEF, GLS, GWI, mitral S', LV outflow tract time velocity integral, forward LVEF and LV ejection time were associated with CV events. After multivariate adjustment only GLS (hazard ratio (HR) = 0.884, p = 0.015) and GWI (HR = 0.927, p = 0.034) remained independently associated with CV events. There was no difference in the incremental prognostic value of GWI compared to GLS (delta -2 log likelihood = 0.8; p = 0.37). In this cohort of heart failure patients with FMR, GLS and GWI were independently associated with cardiovascular events, whereas other systolic performance parameters were not. However, GWI did not outperform GLS, and further research is required to determine the value of these strain-based measures in clinical practice.

Diagnostic and Prognostic Value of Several Color Doppler Jet Grading Methods in Patients With Mitral Regurgitation.

Color Doppler is a widely used ultrasound imaging method for assessing mitral regurgitation (MR) in clinical practice. Nevertheless, color Doppler-based grading of the MR jet has been rarely considered in clinical studies. We investigated the diagnostic and prognostic value of several color Doppler MR jet grading methods and compared them with quantitative grading of MR. The MR color Doppler jet was assessed in 476 MR patients using an 'integrated' eyeballing approach by quantifying the color Doppler jet area, jet area/left atrium area and jet length and using quantitative methods. Clinical endpoints were scored as major adverse clinical events, including cardiovascular death, heart failure hospitalization and mitral valve intervention. When assessed by three echocardiographers, there was a moderate inter-observer agreement for eyeballing color Doppler grade of MR (intraclass correlation coefficient 0.69, p < 0.001). The intra-observer agreement was good for all color Doppler approaches. In primary MR, eyeballing color Doppler correlated well with (in)direct measures of MR severity, with a negative predictive value of 91% when using a grade 2 color Doppler as cut-off. In secondary MR, eyeballing color Doppler grade and jet length were predictors of clinical outcome in Cox proportional hazards analysis (p = 0.003), independent of pulmonary pressures, atrial and ventricular volumes. Overall, the integrated eyeballing approach performed better than color Doppler quantification of the MR jet area and length. In conclusion, this study shows that color Doppler grading of the distal MR jet performs well in predicting events in primary and secondary MR, compared to quantitative grading methods.

A Strain-Based Staging Classification of Left Bundle Branch Block-Induced Cardiac Remodeling.

OBJECTIVES: This study speculated that longitudinal strain curves in left bundle branch block (LBBB) could be shaped by the degree of LBBB-induced cardiac remodeling. BACKGROUND: LBBB independently affects left ventricular (LV) structure and function, but large individual variability may exist in LBBB-induced adverse remodeling. METHODS: Consecutive patients with LBBB with septal flash (LBBB-SF) underwent thorough echocardiographic assessment, including speckle tracking-based strain analysis. Four major septal longitudinal strain patterns (LBBB-1 through LBBB-4) were discerned and staged on the basis of: 1) correlation analysis with echocardiographic indexes of cardiac remodeling, including the extent of SF; 2) strain pattern analysis in cardiac resynchronization therapy (CRT) super-responders; and 3) strain pattern analysis in patients with acute procedural-induced LBBB. RESULTS: The study enrolled 237 patients with LBBB-SF (mean age: 67 ± 13 years; 57% men). LBBB-1 was observed in 60 (26%), LBBB-2 in 118 (50%), LBBB-3 in 29 (12%), and LBBB-4 in 26 (11%) patients. Patients at higher LBBB stages had larger end-diastolic volumes, lower LV ejection fractions, longer QRS duration, increased mechanical dyssynchrony, and more prominent SF compared with less advanced stages (p < 0.001 for all). Among CRT super-responders (n = 30; mean age: 63 ± 10 years), an inverse transition from stages LBBB-3 and -4 (pre-implant) to stages LBBB-1 and -2 (pace-off, median follow-up of 66 months [interquartile range: 32 to 78 months]) was observed (p < 0.001). Patients with acute LBBB (n = 27; mean age: 83 ± 5.1 years) only presented with a stage LBBB-1 (72%) or -2 pattern (24%). CONCLUSIONS: The proposed classification suggests a pathophysiological continuum of LBBB-induced LV remodeling and may be valuable to assess the attribution of LBBB to the extent of LV remodeling and dysfunction.

Proportionate or disproportionate secondary mitral regurgitation: how to untangle the Gordian knot?

Recent randomised percutaneous mitral intervention trials in patients with heart failure with secondary mitral regurgitation (SMR) have yielded contrasting results. A 'relative load' or 'proportionality' conceptual framework for SMR has been proposed to partly explain the disparate results. The rationale behind the framework is that SMR depends on the left ventricular dimension and not vice versa. In this review, we provide an in-depth analysis of the proportionality parameters used in this framework and also discuss the regurgitant fraction. We also consider haemodynamic observations in SMR that may affect the interpretation and comparisons among proportionality parameters. The conclusion is that the proportionality concept remains hypothetical and requires prospective validation before envisaging its use at individual patient level for risk stratification or therapeutic decision-making.

Septal flash: At the heart of cardiac dyssynchrony.

Cardiac resynchronization therapy (CRT) has been a major step in the treatment of heart failure patients and intraventricular conduction delay. As a considerable number of patients do not respond adequately to CRT, echocardiographic dyssynchrony selection criteria have been proposed to improve CRT response, but these parameters eventually failed to provide superior selection of CRT candidates. In the last decade, an echo-dyssynchrony parameter called "septal flash" was been reported by several investigators and opinion leaders in the field of CRT. This parameter has a strong pathophysiological rationale and was shown to be a robust and predominant predictor of CRT response in recent observational and retrospective studies. We here provide a comprehensive and balanced overview of septal flash and address several important aspects, questions and potential future implications of septal flash in cardiomyopathy and CRT.

The Average Pixel Intensity Method and Outcome of Mitral Regurgitation in Mitral Valve Prolapse.

BACKGROUND: Mitral regurgitation (MR) is a frequent consequence of mitral valve prolapse (MVP). However, the echocardiographic grading of MR is challenging, and the recommended grading parameters have several limitations. The authors developed a novel echocardiographic parameter to grade MR, the average pixel intensity (API) method, on the basis of pixel intensity analysis of the continuous-wave Doppler signal. METHODS: Transthoracic echocardiography was performed prospectively in consecutive patients with MVP (N = 149). MR was quantitatively assessed using the API method, vena contracta width, effective regurgitant orifice area, and regurgitant volume. The primary clinical events were cardiovascular mortality, mitral valve surgery, percutaneous mitral intervention, and heart failure hospitalization. RESULTS: The API method was feasible in 90% of all patients with MVP, which was significantly higher than vena contracta width, effective regurgitant orifice area, and regurgitant volume. During a median follow-up period of 17 months, 44 patients (32%) had major adverse cardiac events, and the majority of events occurred in the holosystolic MVP subgroup. The degree of MR severity by the API method was highly significant for the prediction of events. An API cutoff of 111 arbitrary units was defined as "severe" MR due to MVP, with overall superior sensitivity and specificity compared with cutoffs for established MR grading parameters. In patients who did not have major adverse cardiac events during the follow-up period (n = 92), no significant changes in measures of MR severity were found on follow-up echocardiography. CONCLUSIONS: The API method is predictive of clinical events and outcomes in MR due to MVP. Therefore, the API method may be considered for grading the severity of MR due to MVP in clinical practice.

Average pixel intensity method for prediction of outcome in secondary mitral regurgitation.

BACKGROUND: Echocardiographic grading of secondary mitral regurgitation (SMR) severity is challenging and involves multiple guideline-recommended parameters. We previously introduced the average pixel intensity (API) method for grading SMR. In this study, the clinical outcome in SMR based on the API method for grading MR was compared with conventional grading methods. METHODS: 231 patients with systolic heart failure and reduced ejection fraction (ischaemic/non-ischaemic) and SMR were prospectively enrolled. MR was graded using all guideline-recommended parameters and the API method, which is based on the pixel intensity of the continuous wave Doppler signal. The primary outcome was MACE (major adverse cardiac event). RESULTS: The API method was applicable in 98% of patients with SMR (n=227). During a median follow-up of 24 months, 98 patients (43%) had a MACE (cardiovascular mortality (n=50, 22%), heart failure hospitalisation (n=44, 19%), mitral valve surgery (n=11, 5%), percutaneous mitral intervention (n=12, 5%), heart transplantation (n=5, 2%)). On log-rank test, the API method was highly significant in predicting clinical outcome. On multivariable Cox proportional hazard analysis, SMR grading with the API method was an independent predictor of clinical outcome (along with NYHA class and right ventricular systolic pressure; p<0.001), increasing the event risk by 9% per 10 au API rise (p=0.001). In the same multivariable analysis, proximal isovelocity surface area (PISA)-effective regurgitant orifice area or PISA-regurgitant volume were not independent predictors of events (p=0.18 and 0.26, respectively). CONCLUSION: SMR grading with the API method is an independent predictor of clinical outcome and provides prognostic information in addition to clinical and other echocardiographic variables.

Insights into functional mitral regurgitation using the average pixel intensity method.

Previously we introduced and validated the average pixel intensity (API) method for grading mitral regurgitation (MR) in a heterogeneous MR population. We now investigated the feasibility and added value of the API method more specifically in patients with functional MR (FMR). We consecutively enrolled 283 patients with pure FMR. Transthoracic echocardiography was performed and MR was assessed using the API method and guideline-recommended parameters, including color Doppler, vena contracta width (VCW) and proximal isovelocity surface area (PISA)-based methods. The API method had an applicability of 98% in this FMR cohort, which was significantly higher than VCW (84%) and PISA-based methods (75%). Overall, the API method had significant correlations with direct parameters of FMR severity, ejection fraction, atrial and ventricular dimensions, pulmonary pressures and New York Heart Association class. Analysis of the API dynamics during MR revealed a typical pattern with early and late systolic peaks in API and a midsystolic nadir, which matched the temporal changes of the effective regurgitant orifice (ERO) during FMR. Based on ROC curves of established FMR severity cut-offs, an API value of 125 au was considered the optimal cut-off to determine severe MR. Interestingly, this API severity cut-off is similar to the API severity cut-off for MR in degenerative MR (DMR), despite different EROA/RV cut-offs in current ESC guidelines for FMR and DMR. The API method is an easy, fast and feasible parameter for grading FMR and may complement the multiparametric assessment of FMR in daily clinical practice.

Grading of mitral regurgitation in mitral valve prolapse using the average pixel intensity method.

AIMS: We recently reported the feasibility of the average pixel intensity (API) method for grading mitral regurgitation (MR) in a heterogeneous MR population. Since mitral valve prolapse (MVP) is an important cause of primary MR, we more specifically investigated the feasibility of the API method and the MR flow dynamics in patients with MVP. METHODS: Transthoracic echocardiography was performed by a single operator in consecutive MVP patients (n=112). MR was assessed using the API method, color Doppler, vena contracta width (VCW), effective regurgitant orifice area (PISA-EROA) and regurgitant volume (PISA-RV). RESULTS: The API method was feasible in 89% of all MVP patients (68%, 71% for VCW and PISA method, respectively ;p<.001). Inter- and intra-observer correlations for API in MVP with non-holosystolic MR were 0.989 and 0.995. For the overall MVP-MR population, API had significant correlations with direct and indirect measures of MR severity. Based on ROC curves, an API cutoff value of 125 au was suggested to identify severe MR in MVP and a MR duration/systolic time ratio<100% (i.e. non-holosystolic MVP-MR) identifies patients with non-severe MR (API<125), whereas the majority of holosystolic MVP had severe MR (API>125). Finally, API analysis of the proto-, mid- and telesystolic phases of MR in MVP showed different kinetics in non-holosystolic compared to holosystolic MVP. CONCLUSIONS: The API method is a feasible and reproducible method for grading MVP-MR. As the API method takes into account the temporal MR flow changes during the entire systolic cycle, it may be of added value in clinical practice.

Gender differences in electro-mechanical characteristics of left bundle branch block: Potential implications for selection and response of cardiac resynchronization therapy.

BACKGROUND: Female patients are underrepresented in cardiac resynchronization therapy (CRT) trials, although they show better CRT response compared to males and at shorter QRS durations. We hypothesized that differences in left bundle branch block (LBBB) characteristics and mechanical dyssynchrony might explain this gender disparity. METHODS: Patients presenting with true LBBB-morphology (including mid-QRS notching) on surface electrocardiograms (ECG) were selected. LBBB QRS duration (QRSDLBBB) was measured automatically on the ECG. Left ventricular dimensions were assessed by two-dimensional echocardiography. Mechanical dyssynchrony was assessed by the presence of septal flash (SF) on echocardiography. RESULTS: The study enrolled 1037 patients (428 females). Female LBBB patients had smaller QRSDLBBB compared to male LBBB patients (142 [22]ms versus 156 [24]ms, p<0.001). In a multivariate analysis, sex and left ventricular end-diastolic diameter (LVEDD) were independent predictors of QRSDLBBB. QRSDLBBB can be corrected for sex and LVEDD using a simplified formula: corrected-QRSDLBBB=QRSDLBBB+0.5×(50-LVEDD)-10 (if male). SF was more prevalent in females compared to males (60% versus 43%, p<0.001). Women revealed significantly more SF in narrow QRSDLBBB groups compared to men: 65% versus 13% (p<0.001) with QRSDLBBB 120-129ms, 66% versus 18% (p<0.001) with QRSDLBBB 130-139ms and 63% versus 31% (p<0.001) with QRSDLBBB 140-149ms. At QRSDLBBB>150ms, there were no differences in SF prevalence between females and males. CONCLUSION: Female patients show true LBBB morphology at shorter QRSD and have more frequent mechanical dyssynchrony at shorter QRSD compared to males. This might explain the better CRT response rates at shorter QRSD in females.