EASI™ 12­lead ECG with a handheld computer refines cardiovascular diagnosis in general practice.

BACKGROUND: Electrocardiogram (ECG) is used to a small extent in general medicine, because of general practitioner (GP) apprehension about interpretation and time consumption. AIM: This study tested the hypothesis that user-friendly EASI ECG improves GP diagnosis of cardiovascular symptoms. METHOD: Patients over 18 years with recent cardiovascular symptoms or auscultation rhythm abnormalities were included in this prospective, multicentric study (10 practices, 17 GPs). ECG recordings were made with Cardiosecur® (4­lead ECG connected to a handheld computer for EASI™ processing). Besides clinical data, diagnosis/patient referral were noted before and after ECG and interpretation. GP diagnosis and ECG interpretation were compared with a reference diagnosis made by ECG specialist. RESULTS: There were 338 patients; 66% had cardiovascular risk factors. ECGs were performed for chest pain (41%), auscultation rhythm abnormalities (33%) or palpitations (19%). Average time to perform ECG was 4.7 ± 2.1 min, with possible home recordings. Compared with standard ECG, improvement provided by Cardiosecur® was scored 9/10 (range 7-10) by GPs. GPs correctly interpreted ECG normality/abnormality in 77% of patients. Diagnosis was correctly changed for 14% of patients thanks to the ECG, and wrongly changed for 2%. One new appropriate final diagnosis was achieved for 9 ECG recordings (p < 0.001). Diagnostic certainty increased 1.9 ± 2.1/10 (p < 0.001). ECG brought about changes in GP decision making: referral or treatment changed for 82 patients (24%) and complementary test for 69 patients (20%). CONCLUSION: The EASI™ algorithm coupled with a handheld computer facilitates ECG recordings in the primary care setting, providing improved diagnosis.

Periprocedural, early, and long-term risks of pacemaker implantation after atrioventricular nodal re-entry tachycardia ablation: a French nationwide cohort.

AIMS: Pacemaker implantation (PI) after atrioventricular nodal re-entry tachycardia (AVNRT) ablation is a dreadful complication. We aimed to assess periprocedural, early, and late risks for PI. METHODS AND RESULTS: All 27 022 patients who underwent latest AVNRT ablation in France from 2009 to 2017, were identified in the nationwide medicalization database. A control group of 305 152 patients hospitalized for arm, leg, or skin injuries with no history of AVNRT or supraventricular tachycardia were selected. After propensity score matching, both groups had mean age of 53 ± 18 years and were predominantly female (64%). During this 9-year period, 822 of 27 022 (3.0%) AVNRT patients underwent PI, with significant higher risk in propensity-matched AVNRT patients compared to propensity-matched controls [2.9% vs. 0.9%; hazard ratio 3.4 (2.9-3.9), P < 0.0001]. This excess risk was significant during all follow-up, including periprocedural (1st month), early (1-6 months), and late (>6 months) risk periods. Annualized late risk per 100 AVNRT patients was 0.2%. In comparison to controls, excess risk was 0.2% in <30-year-old AVNRT patients; 0.7% in 30-50-year-old; 1.1% in 50-70-year-old and 6.5% over 70-year-olds. Risk for PI was also significantly different according to three procedural factors: centres, experience, and ablation date, with a 30% decrease since 2015. CONCLUSION: Periprocedural, early, and late risks for PI were higher after AVNRT ablation compared to propensity-matched controls. Longer follow-up is needed as the excess risk seems to persist late after AVNRT ablation.

Assessment of left ventricular size and function by 3-dimensional transthoracic echocardiography: Impact of the echocardiography platform and analysis software.

BACKGROUND: Whether echocardiography platform and analysis software impact left ventricular (LV) volumes, ejection fraction (EF), and stroke volume (SV) by transthoracic tridimensional echocardiography (3DE) has not yet been assessed. Hence, our aim was to compare 3DE LV end-diastolic and end-systolic volumes (EDV and ESV), LVEF, and SV obtained with echocardiography platform from 2 different manufacturers. METHODS: 3DE was performed in 84 patients (65% of screened consecutive patients), with equipment from 2 different manufacturers, with subsequent off-line postprocessing to obtain parameters of LV function and size (Philips QLAB 3DQ and General Electric EchoPAC 4D autoLVQ). Twenty-five patients with clinical indication for cardiac magnetic resonance imaging served as a validation subgroup. RESULTS: LVEDV and LVESV from 2 vendors were highly correlated (r = 0.93), but compared with 4D autoLVQ, the use of Qlab 3DQ resulted in lower LVEDV and LVESV (bias: 11 mL, limits of agreement: -25 to +47 and bias: 6 mL, limits of agreement: -22 to +34, respectively). The agreement between LVEF values of each software was poor (intraclass correlation coefficient 0.62) despite no or minimal bias. SVs were also lower with Qlab 3DQ advanced compared with 4D autoLVQ, and both were poorly correlated (r = 0.66). Consistently, the underestimation of LVEDV, LVESV, and SV by 3DE compared with cardiac magnetic resonance imaging was more pronounced with Philips QLAB 3DQ advanced than with 4D autoLVQ. CONCLUSIONS: The echocardiography platform and analysis software significantly affect the values of LV parameters obtained by 3DE. Intervendor standardization and improvements in 3DE modalities are needed to broaden the use of LV parameters obtained by 3DE in clinical practice.

Role of echocardiography before cardiac resynchronization therapy: new advances and current developments.

The role of echocardiography in improving the selection of patients who will benefit from cardiac resynchronization therapy (CRT) remains a source of debate. Although previous landmark reports have demonstrated a link between mechanical dyssynchrony, assessed by delays between left ventricle (LV) walls and response to CRT, the predictive value of these findings has not yet been confirmed in multicenter trials. Indeed, recent studies demonstrated that the classical assessment of LV mechanical dyssynchrony using delay between walls by echocardiography depends not only on LV electrical activation delay (electrical dyssynchrony), but also on abnormalities in regional contractility of the LV and/or loading conditions, which do not represent an appropriate target for CRT. Recent reports highlighted the value of new indices of electromechanical dyssynchrony obtained by echocardiography, to predict LV response and outcome after CRT including septal flash, left bundle branch block-typical pattern by longitudinal strain, apical rocking, septal strain patterns, and systolic stretch index. This was achieved using a mechanistic approach, based on the contractile consequences of electrical dyssynchrony. These indices are rarely found in patients with narrow QRS (<120 ms), whereas their frequency rises in patients with an increase in QRS duration (>120 ms). Theses indices should improve candidate selection for CRT in clinical practice, especially for patients in whom the benefit of CRT remains uncertain, for example, patients with intermediate QRS width (120-150 ms).

Is mechanical dyssynchrony a therapeutic target in heart failure with preserved ejection fraction?

BACKGROUND: Previous studies have found a high frequency of mechanical dyssynchrony in patients with heart failure (HF) with preserved ejection fraction (HFpEF), hence suggesting that cardiac resynchronization therapy (CRT) may be considered in HFpEF. The present study was designed to compare the amount of mechanical dyssynchrony between HFpEF patients and (1) HF with reduced EF (HFrEF) patients with an indication for CRT (HFrEF-CRT(+)) group, (2) HFrEF patients with QRS duration < 120 ms (HFrEF-QRS < 120 ms) group, and (3) hypertensive controls (HTN). METHODS: Electrical (ECG) and mechanical dyssynchrony (atrio-ventricular dyssynchrony, interventricular dyssynchrony, intraventricular dyssynchrony) were assessed using conventional, tissue Doppler, and Speckle Tracking strain echocardiography in 40 HFpEF patients, 40 age- and sex-matched HTN controls, 40 HFrEF-QRS < 120 ms patients, and 40 HFrEF-CRT(+) patients. RESULTS: The frequency of left bundle branch block was low in HFpEF patients (5%) and similar to HTN controls (5%, P = 0.85). Indices of dyssynchrony were similar between HFpEF and HTN patients or HFrEF-QRS < 120 ms patients. In contrast, most indices of dyssynchrony differed between HFpEF and HFrEF-CRT(+) patients. The principal components analysis on the entire cohort of 160 patients yielded 2 homogeneous groups of patients in terms of dyssynchrony, the first comprising HFrEF-CRT(+) patients and the second comprising HTN, HFrEF-QRS < 120 ms and HFpEF patients. CONCLUSIONS: Mechanical dyssynchrony in HFpEF does not differ from that of patients with HTN or patients with HFrEF and a narrow QRS. This data raises concerns regarding the role of dyssynchrony in the pathophysiology of HFpEF and thereby the potential usage of CRT in HFpEF.

Treatment of unexplained syncope: a multicenter, randomized trial of cardiac pacing guided by adenosine 5'-triphosphate testing.

BACKGROUND: The origin of 40% of syncope cases remains unknown even after a complete diagnostic workup. Previous studies have suggested that ATP testing has value in selecting successful therapy. This patient-blinded, multicenter, randomized superiority trial tested whether, in patients with syncope of unknown origin, selecting cardiac pacing in those with a positive ATP test leads to fewer recurrences than those who do not receive pacing. METHODS AND RESULTS: From 2000 to 2005, 80 consenting patients (mean age, 75.9±7.7 years; 81% women; 56% without diagnosed structural heart disease) with syncope of unknown origin and atrioventricular or sinoatrial block lasting >10 seconds (average, 17.9±6.8 seconds) under ATP administration (20-mg IV bolus) were recruited from 10 hospitals, implanted with programmable pacemakers, and randomized to either active pacing (dual-chamber pacing at 70 bpm) or backup pacing (atrial pacing at 30 bpm). Patients were followed up regularly for up to 5 years for any syncope recurrence, the primary outcome. Mean follow-up was 16 months. Syncope recurred in 8 of 39 patients (21%) randomized to active pacing and in 27 of 41 (66%) randomized to backup pacing (control), yielding a hazard ratio of 0.25 (95% confidence interval, 0.12-0.56). After recurrence, the 27 recurrent control patients were reprogrammed to active pacing, and only 1 reported subsequent syncope. CONCLUSION: This study suggests that, in elderly patients with syncope of unknown origin and positive ATP tests, active dual-chamber pacing reduces syncope recurrence risk by 75% (95% confidence interval, 44-88). CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com/ISRCTN00029383. Unique identifier: ISRCTN00029383.

Cardiac resynchronization therapy as rescue therapy in end-stage heart failure: illustration by three-dimensional speckle tracking strain echocardiography.

We report the case of a 73-year-old man admitted for refractory heart failure following implantation of a dual-chamber pacemaker. Three-dimensional (3D) echocardiography with speckle tracking area strain identified severe left ventricular (LV) dysfunction and LV dyssynchrony following right ventricular pacing. As the patient's clinical condition rapidly worsened despite optimal medical treatment, a cardiac resynchronization therapy (CRT) pacemaker was successfully implanted as rescue therapy. Symptoms rapidly regressed and echocardiographic assessment following CRT demonstrated an immediate improvement in LV systolic function, confirmed at 9-month follow-up with evidence of reverse remodeling. New imaging technologies such as 3D echocardiography with speckle tracking area strain may help to identify and follow up patients who will benefit from CRT as rescue therapy.

Functional mitral regurgitation: a link to pulmonary hypertension in heart failure with preserved ejection fraction.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) may present with Pulmonary hypertension (PH) and functional mitral regurgitation (MR). Whether PH is linked to the presence of functional MR has not been investigated in HFpEF patients. METHODS AND RESULTS: Systolic pulmonary artery pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control subjects free of organic mitral valve lesions, significant valve disease, and comorbid conditions associated with PH. Whereas none of control subjects had more than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective regurgitant orifice, regurgitant volume, and regurgitant fraction 7 ± 3 mm,(2) 15 ± 8 mL, and 28 ± 14%, respectively). Pulmonary hypertension (sPAP >35 mm Hg) was significantly more prevalent in HFpEF patients with functional MR than in HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR remained an independent predictor of PH in HFpEF patients (P = .004) after adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022) and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in HFpEF patients than in control subjects (35 ± 9 vs 29 ± 8 mm Hg [P < .0001] and 13 ± 6 vs 11 ± 5 [P = .018], respectively). Systolic PAP remained greater in HFpEF patients than in control subjects after adjusting for E/e' (P = .002). CONCLUSIONS: Pulmonary hypertension appears to be linked to the presence of functional MR in HFpEF patients.

Clinical and echocardiographic correlates of plasma B-type natriuretic peptide levels in patients with aortic valve stenosis and normal left ventricular ejection fraction.

BACKGROUND: Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction. METHOD AND RESULTS: One hundred thirty-five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty-nine patients (66%) had severe AVS (aortic valve area <0.6 cm(2) /m(2) BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R(2) = 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R(2) = 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R(2) = 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003). CONCLUSIONS: In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se.

Clinical and prognostic implications of phenomapping in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Despite having an indication for cardiac resynchronization therapy according to current guidelines, patients with heart failure with reduced ejection fraction who receive cardiac resynchronization therapy do not consistently derive benefit from it. AIM: To determine whether unsupervised clustering analysis (phenomapping) can identify distinct phenogroups of patients with differential outcomes among cardiac resynchronization therapy recipients from routine clinical practice. METHODS: We used unsupervised hierarchical cluster analysis of phenotypic data after data reduction (55 clinical, biological and echocardiographic variables) to define new phenogroups among 328 patients with heart failure with reduced ejection fraction from routine clinical practice enrolled before cardiac resynchronization therapy. Clinical outcomes and cardiac resynchronization therapy response rate were studied according to phenogroups. RESULTS: Although all patients met the recommended criteria for cardiac resynchronization therapy implantation, phenomapping analysis classified study participants into four phenogroups that differed distinctively in clinical, biological, electrocardiographic and echocardiographic characteristics and outcomes. Patients from phenogroups 1 and 2 had the most improved outcome in terms of mortality, associated with cardiac resynchronization therapy response rates of 81% and 78%, respectively. In contrast, patients from phenogroups 3 and 4 had cardiac resynchronization therapy response rates of 39% and 59%, respectively, and the worst outcome, with a considerably increased risk of mortality compared with patients from phenogroup 1 (hazard ratio 3.23, 95% confidence interval 1.9-5.5 and hazard ratio 2.49, 95% confidence interval 1.38-4.50, respectively). CONCLUSIONS: Among patients with heart failure with reduced ejection fraction with an indication for cardiac resynchronization therapy from routine clinical practice, phenomapping identifies subgroups of patients with differential clinical, biological and echocardiographic features strongly linked to divergent outcomes and responses to cardiac resynchronization therapy. This approach may help to identify patients who will derive most benefit from cardiac resynchronization therapy in "individualized" clinical practice.

Clinical Significance of Global Wasted Work in Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: The relationship between myocardial work assessment using pressure-strain loops by echocardiography before cardiac resynchronization therapy (CRT) and response to CRT has been recently revealed. Among myocardial work parameters, the impact of left ventricular myocardial global wasted work (GWW) on response to CRT and outcome following CRT has been seldom studied. Hence, the authors evaluated the relationship between preprocedural GWW and outcome in a large prospective cohort of patients with heart failure (HF) and reduced ejection fraction receiving CRT. METHODS: The study included 249 patients with HF. Myocardial work indices including GWW were calculated using speckle-tracking strain two-dimensional echocardiography using pressure-strain loops. End points of the study were (1) response to CRT, defined as left ventricular reverse remodeling and/or absence of hospitalization for HF, and (2) all-cause death during follow-up. RESULTS: Median follow-up duration was 48 months (interquartile range, 43-54 months). Median preoperative GWW was 281 mm Hg% (interquartile range, 184-388 mm Hg%). Preoperative GWW was associated with CRT response (area under the curve, 0.74; P < .0001), and a 200 mm Hg% threshold discriminated CRT nonresponders from responders with 85% specificity and 50% sensitivity, even after adjustment for known predictors of CRT response (adjusted odds ratio, 4.03; 95% CI, 1.91-8.68; P < .001). After adjustment for established predictors of outcome in patients with HF with reduced ejection fraction receiving CRT, GWW < 200 mm Hg% remained associated with a relative increased risk for all-cause death compared with GWW ≥ 200 mm Hg% (adjusted hazard ratio, 2.0; 95% CI, 1.1-3.9; P = .0245). Adding GWW to a baseline model including known predictors of outcome in CRT resulted in an improvement of this model (χ2 to improve 4.85, P = .028). The relationship between GWW and CRT response and outcome was stronger in terms of size effect and statistical significance than for other myocardial work indices. CONCLUSIONS: Low preoperative GWW (<200 mm Hg%) is associated with absence of CRT response in CRT candidates and with a relative increased risk for all-cause death. GWW appears to be a promising parameter to improve selection for CRT of patients with HF with reduced ejection fraction.

Impact of Increased Right Atrial Size on Long-Term Mortality in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy.

The ability to visualize the right atrium (RA) by echocardiography allows a quantitative, highly reproducible assessment of the RA volume (RAV). The aim of this study is to evaluate the relation between RAV and long-term mortality in a prospective cohort of heart failure and reduced ejection fraction patients in sinus rhythm receiving cardiac resynchronization therapy. 172 patients were included. The right atrium volume index (RAVI) was calculated using Simpson's method from the apical four-chamber view and indexed to body surface area. The relation between RAVI and mortality during follow up was studied. Median follow up was 68 months (interquartile range 62 to 73 months). Mean RAVI was 27 ± 14 mL/m² (IQR 22 to 33 mL/m²). Cumulative 5-year all-cause mortality was 22 ± 6% in patients with RAVI ≤ 19 mL/m², 24 ± 6% for RAVI 19 to 29 mL/m² and 58 ± 7% for RAVI >29 mL/m² (p for trend <0.001). After adjustment on clinical and echocardiographic predictors of outcome including indices of right ventricular function, there was a significant increase in overall mortality risk with increasing RAVI (adjusted hazard ratio 1.02 [95% confidence interval, 1.00 to 1.03], per 1 mL/m2 increment; p = 0.042). Patients in the highest tertile (RAVI >29 mL/m²) had significantly greater risk of death compared with those with RAVI ≤29 mL/m² (adjusted hazard ratio 2.01 [95% confidence interval, 1.15 to 3.50]; p = 0.014). In conclusion, RA enlargement is a powerful and highly reproducible independent predictor of long-term mortality in patients with heart failure and reduced ejection fraction in sinus rhythm receiving cardiac resynchronization therapy.

Correlates of the ratio of acceleration time to ejection time in patients with aortic stenosis: An echocardiographic and computed tomography study.

BACKGROUND: An increased acceleration time to ejection time (AT/ET) ratio is associated with increased mortality in patients with aortic stenosis (AS). AIM: To identify the factors associated with an increased AT/ET ratio. METHODS: The relationships between the AT/ET ratio and clinical and Doppler echocardiographic variables of interest in the setting of AS were analysed retrospectively in 1107 patients with AS and preserved left ventricular (LV) ejection fraction (LVEF). The computed tomography aortic valve calcium (CT-AVC) score was studied in a subgroup of 342 patients. RESULTS: In the univariate analysis, the AT/ET ratio was found to correlate with peak aortic jet velocity (r=0.57; P<0.0001), mean pressure gradient (r=0.60; P<0.0001), aortic valve area (r=-0.50; P<0.0001) and CT-AVC score (r=0.24; P<0.0001). The AT/ET ratio had good accuracy in predicting a peak aortic jet velocity≥4 m/s, a mean pressure gradient≥40mmHg and an aortic valve area≤1.0cm2, with an optimal cut-off value of 0.34. Multivariable linear regression analysis showed that presence of AS-related symptoms, decreased LV stroke volume index, LVEF, absence of diabetes mellitus, systolic blood pressure, increased LV mass index, relative wall thickness and peak aortic jet velocity were independently associated with an increased AT/ET ratio (all P<0.05). In the subgroup of patients who underwent CT-AVC scoring, the CT-AVC score was independently associated with an increased AT/ET ratio (P<0.05). CONCLUSIONS: The AT/ET ratio is related to echocardiographic and CT-AVC indices of AS severity. However, multiple intricate factors beyond the haemodynamic and anatomical severity of AS influence the AT/ET ratio, including LV geometry, function and systolic blood pressure. These findings should be considered when assessing the AT/ET ratio in patients with AS and preserved LVEF.

Clinical Significance of Electromechanical Dyssynchrony and QRS Narrowing in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: We hypothesized that preoperative electromechanical dyssynchrony amenable to cardiac resynchronization therapy (CRT) and QRS narrowing immediately after CRT are both correlated and have a cumulative impact on response and outcome after CRT. METHODS: A total of 233 CRT candidates (heart failure New York Heart Association classes II-IV, ejection fraction < 35%, QRS ≥ 120 milliseconds, 44% women, 71 ± 11 years old) were prospectively included. Preoperative electromechanical dyssynchrony amenable to CRT was assessed by septal deformation patterns using speckle tracking echocardiography. QRS narrowing was calculated from 12-lead electrocardiograms before and immediately after CRT implantation. The primary endpoint was overall mortality during long-term follow-up. The NTC clinical trial number is NCT02986633. RESULTS: Eighty-seven percent of patients with preoperative electromechanical dyssynchrony experienced QRS narrowing after CRT (118/136), whereas 69% of patients without preoperative electromechanical dyssynchrony (67/97) experienced QRS narrowing after CRT (P < 0.001). By Cox multivariate analysis, both preoperative electromechanical dyssynchrony and lack of postoperative QRS narrowing were independently associated with an increased risk of mortality during follow-up (adjusted hazards ratio [HR] 2.24, 95% confidence interval [CI] 1.43-3.50 and HR 1.90, 95% CI 1.06-3.38, respectively). Compared with patients with preoperative electromechanical dyssynchrony, patients without both electromechanical dyssynchrony and postoperative QRS narrowing experienced a considerable increased risk of mortality during follow-up (adjusted HR 3.70, 95% CI 1.96-6.97). CONCLUSIONS: Lack of postoperative QRS narrowing after CRT is associated with preoperative electromechanical dyssynchrony. Both preoperative electromechanical dyssynchrony and postoperative QRS narrowing have a favourable cumulative impact on outcome after CRT.

Time course of secondary mitral regurgitation in patients with heart failure receiving cardiac resynchronization therapy: Impact on long-term outcome beyond left ventricular reverse remodelling.

BACKGROUND: The prognostic value of secondary mitral regurgitation (MR) at baseline versus immediately after and several months after cardiac resynchronization therapy (CRT), beyond left ventricular (LV) reverse remodelling, has yet to be investigated. AIM: To evaluate the clinical significance of secondary MR before and at two timepoints after CRT in a large cohort of consecutive patients with heart failure (HF) and reduced LV ejection fraction. METHODS: A total of 198 patients were recruited prospectively into a registry, and underwent echocardiography at baseline and immediately after CRT (on the day of hospital discharge). Echocardiography was also performed 9 months after CRT in 172 patients. The impact of significant secondary MR (≥moderate) on all-cause death, cardiovascular death and hospitalization for HF was studied at each stage. RESULTS: The frequency of significant secondary MR decreased from 23% (n=45) to 8% (n=16) immediately after CRT. Among the 172 patients who underwent echocardiography 9 months after CRT, 17 (10%) had significant secondary MR. During a median follow-up of 48 months, 49 patients died and 36 were hospitalized for HF. Patients with significant secondary MR immediately after or 9 months after CRT had an increased risk of all-cause death, cardiovascular death and hospitalization for HF during follow-up (P<0.05 for all endpoints). After adjustment for LV reverse remodelling, significant secondary MR 9 months after CRT remained associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 3.77; P=0.014), cardiovascular death (adjusted HR 5.36; P=0.037), and hospitalization for HF (adjusted HR 7.33; P=0.001). CONCLUSIONS: Significant secondary MR despite CRT provides important prognostic information beyond LV reverse remodelling. Further studies are needed to evaluate the potential role of new percutaneous procedures for mitral valve repair in improving outcome in these very high-risk patients.

Prospective assessment of the frequency of low gradient severe aortic stenosis with preserved left ventricular ejection fraction: Critical impact of aortic flow misalignment and pressure recovery phenomenon.

BACKGROUND: The frequency of paradoxical low-gradient severe aortic stenosis (AS) varies widely across studies. The impact of misalignment of aortic flow and pressure recovery phenomenon on the frequency of low-gradient severe AS with preserved left ventricular ejection fraction (LVEF) has not been evaluated in prospective studies. AIMS: To investigate prospectively the impact of aortic flow misalignment by Doppler and lack of pressure recovery phenomenon correction on the frequency of low-gradient (LG) severe aortic stenosis (AS) with preserved LVEF. METHODS: Aortic jet velocities and mean pressure gradient (MPG) were obtained by interrogating all windows in 68 consecutive patients with normal LVEF and severe AS (aortic valve area [AVA] ≤1cm2) on the basis of the apical imaging window alone (two-dimensional [2D] apical approach). Patients were classified as having LG or high-gradient (HG) AS according to MPG <40mmHg or ≥40mmHg, and normal flow (NF) or low flow (LF) according to stroke volume index >35mL/m2 or ≤35mL/m2, on the basis of the 2D apical approach, the multiview approach (multiple windows evaluation) and AVA corrected for pressure recovery. RESULTS: The proportion of LG severe AS was 57% using the 2D apical approach alone. After the multiview approach and correction for pressure recovery, the proportion of LG severe AS decreased from 57% to 13% (LF-LG severe AS decreased from 23% to 3%; NF-LG severe AS decreased from 34% to 10%). As a result, 25% of patients were reclassified as having HG severe AS (AVA ≤1cm2 and MPG ≥40mmHg) and 19% as having moderate AS. Hence, 77% of patients initially diagnosed with LG severe AS did not have "true" LG severe AS when the multiview approach and the pressure recovery phenomenon correction were used. CONCLUSIONS: Aortic flow misevaluation, resulting from lack of use of multiple windows evaluation and pressure recovery phenomenon correction, accounts for a large proportion of incorrectly graded AS and considerable overestimation of the frequency of LG severe AS with preserved LVEF.

Relationship between exercise pressure gradient and haemodynamic progression of aortic stenosis.

BACKGROUND AND AIMS: We hypothesized that large exercise-induced increases in aortic mean pressure gradient can predict haemodynamic progression during follow-up in asymptomatic patients with aortic stenosis. METHODS: We retrospectively identified patients with asymptomatic moderate or severe aortic stenosis (aortic valve area<1.5cm2 or<1cm2) and normal ejection fraction, who underwent an exercise stress echocardiography at baseline with a normal exercise test and a resting echocardiography during follow-up. The relationship between exercise-induced increase in aortic mean pressure gradient and annualised changes in resting mean pressure gradient during follow-up was investigated. RESULTS: Fifty-five patients (mean age 66±15 years; 45% severe aortic stenosis) were included. Aortic mean pressure gradient significantly increased from rest to peak exercise (P<0.001). During a median follow-up of 1.6 [1.1-3.2] years, resting mean pressure gradient increased from 35±13mmHg to 48±16mmHg, P<0.0001. Median annualised change in resting mean pressure gradient during follow-up was 5 [2-11] mmHg. Exercise-induced increase in aortic mean pressure gradient did correlate with annualised changes in mean pressure gradient during follow-up (r=0.35, P=0.01). Hemodynamic progression of aortic stenosis was faster in patients with large exercise-induced increase in aortic mean pressure gradient (≥20mmHg) as compared to those with exercise-induced increase in aortic mean pressure gradient<20mmHg (median annualised increase in mean pressure gradient 19 [6-28] vs. 4 [2-10] mmHg/y respectively, P=0.002). Similar results were found in the subgroup of 30 patients with moderate aortic stenosis. CONCLUSION: Large exercise-induced increases in aortic mean pressure gradient correlate with haemodynamic progression of stenosis during follow-up in patients with asymptomatic aortic stenosis. Further studies are needed to fully establish the role of ESE in the decision-making process in comparison to other prognostic markers in asymptomatic patients with aortic stenosis.

Asymptomatic aortic stenosis: An assessment of patients' and of their general practitioners' knowledge, after an indexed specialized assessment in community practice.

BACKGROUND: Clinical and echocardiography follow-up is recommended in patients with aortic stenosis to detect symptom onset, thus a watchful waiting approach has to be safe and effective. For both AS patients and their general practitioners, evaluation of valvular heart disease (VHD) knowledge, after the indexed specialized assessment has never been measured. AIMS: To evaluate the knowledge of clinical symptoms of aortic stenosis by both patients and their general practitioner. METHODS: Sixty-four patients, with moderate to severe and initially asymptomatic AS (median AVA (interquartile range) 1.01(0.80-1.15) cm2) previously referred to a tertiary center and medically managed for at least 6 months after the index echocardiogram, and their primary care doctors were interviewed on the phone and asked to answer specific questions related to knowledge of aortic stenosis symptoms. RESULTS: Fifty-six percent of patients quoted shortness of breath as one of the aortic stenosis symptoms, and only 16% knew the 3 aortic stenosis symptoms. Fifty percent of patients reported having received sufficient information regarding aortic stenosis; only 48% remembered receiving information regarding specific symptoms. Only 14% general practitioners quoted the 3 specific symptoms. According to the initial recommendation, only 41 patients (64%) benefitted from a 6-to-12 month clinical and echocardiography follow up. CONCLUSION: GPs are not sufficiently trained to safely manage AS patients in the community and to ensure adequate follow-up and monitoring. AS patients were not properly informed about their diagnosis and symptomatology. Hence, therapeutic education should be improved for patients with asymptomatic AS and continuous medical education on VHD should be reinforced, for GPs.

Correction: Asymptomatic aortic stenosis: An assessment of patients' and of their general practitioners' knowledge, after an indexed specialized assessment in community practice.

[This corrects the article DOI: 10.1371/journal.pone.0179988.].

Clinical significance of septal deformation patterns in heart failure patients receiving cardiac resynchronization therapy.

AIMS: Specific septal motion related to dyssynchrony is strongly linked to reverse remodelling, in patients with systolic heart failure (HF) receiving cardiac resynchronization therapy (CRT). We aimed to investigate the relationship between septal deformation patterns studied by longitudinal speckle tracking and clinical outcome following CRT. METHODS AND RESULTS: A total of 284 CRT candidates from two centres (HF NYHA classes II-IV, ejection fraction < 35%, QRS ≥ 120 ms) were prospectively included. Longitudinal strain of the septum in the apical four-chamber view determined three patterns of septal contraction. The endpoints were overall mortality, cardiovascular mortality, and hospitalization for HF. Compared with patterns 1 or 2, pattern 3 was associated with an increased risk for both overall and cardiovascular mortality [hazard ratio (HR) = 3.78, 95% confidence interval (CI): 1.85-7.75, P < 0.001 and HR = 3.84, 95% CI: 1.45-10.16, P = 0.007, respectively] and HF hospitalization (HR = 4.41, 95% CI: 2.18-8.90, P < 0.001). Addition of septal patterns to multivariable models, including baseline QRS width and presence of left bundle branch block, improved risk prediction, and discrimination. In patients with intermediate QRS duration (120-150 ms), pattern 3 remained associated with a worse outcome than pattern 1 or 2 (P < 0.05 for all endpoints). CONCLUSION: The identification of septal deformation patterns provides important prognostic information in CRT candidates in addition to ordinary clinical, electrocardiographic, and echocardiographic predictors of outcome in HF patients. This parameter may be particularly useful in patients with intermediate QRS duration in whom the benefit of CRT remains uncertain.