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Conduction disturbances after transcatheter aortic valve implantation (TAVI) are common, heterogeneous, and frequently result in permanent pacemaker implantation (PPI). Pacemaker therapy with a high rate of right ventricular pacing is associated with heart failure, hospitalizations, and reduced quality of life.The purpose of this study was to compare medium-term outcomes between PPI implantation strategies, as choosing the right indication for PPI is still an area of uncertainty and information on outcomes of PPI regimens beyond 1 year is rare.We compared outcomes after 3 years between a restrictive PPI strategy, in which the lowest threshold for PPI was left bundle branch block (LBBB) (QRS120 ms) with the presence of new atrioventricular block (PQ200 ms), and a liberal PPI regimen, in which PPI already was performed in patients with new-onset LBBB.Between January 2014 and December 2016, TAVI was performed in 884 patients at our center. Of these, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs 38.1%; P.001). The incidence of the primary endpoint (all-cause-mortality and hospitalization for heart failure) after 3 years was similar in both groups (30.7% vs 35.2%; P = .242), as was all-cause-mortality (26.6% vs 29.2%; P = .718). Overall, patients who required PPI post-TAVI had significantly more hospitalizations due to heart failure (14.8% vs 7.8%; P = .004).A restrictive PPI strategy after TAVI reduces PPI significantly and is safe in medium-term follow-up over 3 years.

OBJECTIVES Abnormal invasive exercise haemodynamics in asymptomatic patients with severe mitral regurgitation were associated with higher regurgitation burden. We analysed the association between parameters of invasive exercise testing with mortality and valve surgery compared to guideline defined non-invasive criteria. METHODS This single centre, retrospective cohort study assesses the association of invasive exercise haemodynamics and mortality with and without surgery in patients with severe mitral regurgitation and normal ejection fraction (≥55%) as primary outcome. The secondary outcome was the need for mitral valve surgery in 113 asymptomatic patients primarily managed conservatively. RESULTS We identified 314 patients [age 59 years (standard deviation 13), 27% female] with available exercise haemodynamics with a median follow-up of 8.2 (interquartile range 5.2–11.2) years. Five-year survival rate was 93.0%. Pulmonary capillary wedge pressure at maximum exercise >30 mmHg was the only parameter independently associated with mortality after adjustment for age and guideline criteria [hazard ratio (HR) 2.7 (1.3–5.6), P = 0.007]. In the 113 patients primarily managed conservatively, maximum pulmonary capillary wedge pressure was independently associated with mitral valve surgery during follow-up in multivariable analysis (HR 2.10 (1.32–3.34), P = 0.002; after adjustment for workload and weight: HR 1.31 (1.14–1.52), P 25 mmHg improved the predictive power of current guideline criteria for surgery (area under the curve 0.61–0.68, P = 0.02). CONCLUSIONS Invasive exercise haemodynamics predict mortality and improve prognostic information about surgery during follow-up derived from current guideline criteria in asymptomatic patients with severe mitral regurgitation.

Background Relevant atrial cardiomyopathy (ACM), defined as a left atrial (LA) low-voltage area ≥ 2 cm2 at 0.5 mV threshold on endocardial contact mapping, is associated with new-onset atrial fibrillation (AF), higher arrhythmia recurrence rates after pulmonary vein isolation (PVI), and an increased risk of stroke. The current study aimed to assess two non-invasive echocardiographic parameters, LA emptying fraction (EF) and LA longitudinal strain (LAS, during reservoir (LASr), conduit (LAScd) and contraction phase (LASct)) for the diagnosis of ACM and prediction of arrhythmia outcome after PVI. Methods We prospectively enrolled 60 consecutive, ablation-naive patients (age 66 ± 9 years, 80% males) with persistent AF. In 30 patients (derivation cohort), LA-EF and LAS cut-off values for the presence of relevant ACM (high-density endocardial contact mapping in sinus rhythm prior to PVI at 3000 ± 1249 sites) were established in sinus rhythm and tested in a validation cohort (n = 30). Arrhythmia recurrence within 12 months was documented using 72-h Holter electrocardiograms. Results An LA-EF of Conclusion The echocardiographic parameters LA-EF and LAS allow accurate, non-invasive diagnosis of ACM and prediction of arrhythmia recurrence after PVI. Graphic abstract

OBJECTIVES We sought to assess the safety of a restrictive permanent pacemaker implantation (PPI) strategy after transcatheter aortic valve implantation (TAVI) as compared to a liberal strategy. BACKGROUND Conduction disturbances resulting in PPI are common after TAVI. However, conduction disturbances may be transient and PPI may be superfluous in some patients. METHODS Until August 2015, we performed PPI in all patients with new complete left bundle branch block (LBBB, QRS > 120 milliseconds) or higher degree atrioventricular (AV) blocks (liberal strategy). From September 2015 onwards, LBBB established an indication for PPI only in the presence of new-onset AV block (PQ > 200 milliseconds) (restrictive strategy). We analyzed the impact of the restrictive strategy on pacemaker implantation rate, duration of hospital stay, and 1-year mortality. RESULTS Between January 2014 and December 2016, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs. 38.1%, p

Background Low prosthesis position after transcatheter aortic valve implantation (TAVI) is associated with higher rates of new onset conduction disturbances and permanent pacemaker implantations. Purpose of this study was to investigate possible predictors of a low prosthesis position of the SAPIEN 3 (Edwards Lifesciences, Irvine, California, USA) valve type using fusion imaging of pre- and post-procedural computed tomography angiography (CTA). Methods CTA fusion imaging was performed in 120 TAVI-patients with 3D-reconstruction of the transcatheter heart valve (THV) position within the device landing zone. A low implantation position was defined according to the manufacturer’s recommendations as > 30% of the prosthesis below the native annulus plane. Results A low THV position was found in 17 patients (14%). Patients with low THV position had less calcification of the annulus region and a smaller annulus size compared to patients with a normal or high THV position (P = 0.003 and 0.041, respectively). The only independent predictor of a low THV position in multivariate logistic regression analysis was the extent of calcification of the cusp region (odds ratio [CI] 0.842 [0.727–0.976], P = 0.022). Conclusions Fusion imaging of pre-and post-procedural CTA identified reduced calcification of the cusp region as an independent predictor of a low THV position of the SAPIEN 3. This should be considered when planning the TAVI procedure. Graphic abstract Correlation of cusp region calcification and prosthesis position after TAVI

AimsAtrial fibrosis contributes to arrhythmogenesis in atrial fibrillation and can be detected by MRI or electrophysiological mapping. The current study compares the spatial correlation between delayed enhancement (DE) areas to low-voltage areas (LVAs) and to arrhythmogenic areas with spatio-temporal dispersion (ST-Disp) or continuous activity (CA) in atrial fibrillation (AF).Methods and resultsSixteen patients with persistent AF (nine long-standing) underwent DE-magnetic resonance imaging (1.25 mm × 1.25 mm × 2.5 mm) prior to pulmonary vein isolation. Left atrial (LA) voltage mapping was acquired in AF and the regional activation patterns of 7680 AF wavelets were analysed. Sites with ST-Disp or CA were characterized (voltage, duration) and their spatial relationship to DE areas and LVAs 0.5 mV). Spatio-temporal dispersion and CA more frequently co-localized with LVAs than with DE areas (78% vs. 63%, P = 0.02). Regional bipolar voltage of ST-Disp vs. CA was 0.64 ± 0.47 mV vs. 0.58 ± 0.51 mV. All 28 ST-Disp and 56 CA areas contained electrograms with prolonged duration (115 ± 14 ms) displaying low voltage (0.34 ± 0.11 mV).ConclusionA small portion of DE areas and LVAs harbour the arrhythmogenic areas displaying ST-Disp or CA. Most arrhythmogenic activities co-localized with LVAs, while there was less co-localization with DE areas. There is an important mismatch between DE areas and LVAs which needs to be considered when used as target for catheter ablation.

AIMS Sinus rhythm restoration (SRR) in patients with atrial fibrillation (AF) and heart failure may improve systolic function and impact on consecutive clinical management, but time course and potential predictors of response to SRR are uncertain. METHODS AND RESULTS We prospectively studied 50 consecutive patients who presented in heart failure with reduced ejection fraction (EF) and concomitant AF. After exclusion of valvular and coronary artery disease patients underwent electrical cardioversion. Serial echocardiography, cardiac magnetic resonance imaging (cMRI), and 24-h electrocardiograms were performed at baseline, and on Days 3 and 40 following SRR. Baseline left ventricular EF of the study population (76% male, age 69 ± 11 years) was 30 ± 7%. Sustained SRR (≥3 days) significantly improved EF (Day 3: 43 ± 7%, n = 46; Day 40: 53 ± 9%, n = 34; P

We sought to evaluate haemodynamic prosthetic valve performance in patients with early leaflet thrombosis (LT) after transcatheter aortic valve implantation (TAVI). In this retrospective observational study, 59 patients with LT underwent clinical and echocardiographic follow-up. During a median follow-up of 383 days 41 patients received antiplatelet therapy (APT-group) and 18 patients oral anticoagulation due to atrial fibrillation (AC-group). The mean pressure gradient (MPG) at baseline did not differ between groups (P = 0.875). During follow-up, MPG increased from 11.0 (9.0; 14.5) to 13.0 mmHg (10.0; 18.0)_ in the APT-group (P = 0.010) but remained unchanged in the AC-group (P = 0.297) resulting in a significantly higher MPG in patients on antiplatelet therapy (P = 0.024). Similarly, change of MPG per year was significantly higher in the APT-group [1.4 (− 0.9; 7.0) vs. − 0.6 (− 2.5; 1.1), P = 0.014]. Seven (17.1%) patients in the APT-group and two(11.1%) patients in the AC-group developed MPGs of at least 20 mmHg (P = 0.558). Three patients (7.3%) in the APT- and none in the AC-group developed symptoms of obstructive thrombosis (P = 0.239). In our adjusted analysis, only lack of anticoagulation was significantly associated with change in gradients during follow-up (P = 0.012). In patients with LT, antiplatelet-, but not anticoagulant therapy, was associated with significant increases in MPG, which may lead to symptomatic obstructive valve thrombosis.

Aims Atrial cardiomyopathy (ACM) is associated with new-onset atrial fibrillation, arrhythmia recurrence after pulmonary vein isolation (PVI) and increased risk for stroke. At present, diagnosis of ACM is feasible by endocardial contact mapping of left atrial (LA) low-voltage substrate (LVS) or late gadolinium-enhanced magnetic resonance imaging, but their complexity limits a widespread use. The aim of this study was to assess non-invasive body surface electrocardiographic imaging (ECGI) as a novel clinical tool for diagnosis of ACM compared with endocardial mapping. Methods and results Thirty-nine consecutive patients (66 ± 9 years, 85% male) presenting for their first PVI for persistent atrial fibrillation underwent ECGI in sinus rhythm using a 252-electrode-array mapping system. Subsequently, high-density LA voltage and biatrial activation maps (mean 2090 ± 488 sites) were acquired in sinus rhythm prior to PVI. Freedom from arrhythmia recurrence was assessed within 12 months follow-up. Increased duration of total atrial conduction time (TACT) in ECGI was associated with both increased atrial activation time and extent of LA-LVS in endocardial contact mapping (r = 0.77 and r = 0.66, P Conclusion Analysis of TACT in non-invasive ECGI allows diagnosis of patients with ACM, which is associated with a significantly increased risk for arrhythmia recurrence following PVI.

Background Reduced flow rate and stroke volume are a common finding in patients with severe aortic stenosis. The aim of this study was to assess their impact on mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Methods A total of 1080 patients with severe aortic stenosis who underwent TAVI between 2007 and 2017 were followed for a mean of 2.4±1.6 years. Patients were allocated into two groups according to flow rate (cut-off 200mL/s), 805 patients had a normal flow rate and 275 patients had reduced flow rate. Long-term survival was summarized using Kaplan-Meier curves and Cox-regression models. Results Patients with reduced flow rate were older (83.8±5.5 years; P Conclusion Patients with a reduced flow rate exhibit an increased mortality even after TAVI (similar to patients with reduced SVI) and should therefore be carefully evaluated in the heart-team. PostTAVI survival according to flow rate Funding Acknowledgement Type of funding source: None

Background The role of invasive exercise hemodynamics in the management of asymptomatic patients with severe primary mitral regurgitation (MR) is unclear. Methods and results We compared the predictive power of parameters of invasive exercise testing for future valve surgery to guideline-defined non-invasive criteria. Maximal pulmonary capillary wedge pressure (PCWP), PCWP normalized to workload and weight (PCWL), and invasive maximal systolic pulmonary artery pressure (SPAP) were assessed in 113 asymptomatic patients with severe primary MR between 1996 and 2012. Mean age was 52±11 years, 16% were female, ejection fraction was ≥55% in all patients. During a median follow up of 4.5 years (IQR2.0; 8.3) 54 patients (48%) underwent valve surgery. In univariate analysis PCWP (P25mmHg to a Cox regression model based on non-invasive guideline criteria resulted in a significant increase in the area under the curve (0.61 to 0.68, P=0.02). Conclusion In asymptomatic patients with severe primary mitral regurgitation and preserved left ventricular function invasive exercise hemodynamics improves information derived from current non-invasive guideline criteria. Figure 1 Funding Acknowledgement Type of funding source: None

Background Early leaflet thrombosis (LT) is a well described phenomenon after transcatheter aortic valve implantation (TAVI) with an incidence between 10 and 16%. So far, data about predictors of LT are scarce. Purpose The purpose of the study was to investigate the influence of prosthesis related factors on the occurrence of LT. Methods Fusion imaging of pre- and post-procedural CTA was performed in 140 TAVI-patients (55 with LT, 85 without LT) to obtain a 3D-reconstruction of the transcatheter heart valve (THV) within the native annulus region. All patients received a balloon-expandable Sapien 3 THV. The length of the THV above and below the native annulus was measured within the fused images to assess the implantation depth. The deployed THV area was quantified on three heights (left ventricular outflow tract end, center of the stent, aortic end) to determine the average expansion of the prosthesis as percent of the nominal area. We also calculated the extent of prosthesis waist in percent of maximum area. The stent tilt was determined in relation to the annulus plane. Results After multivariate adjustment the extent of THV expansion (odds ratio per 10 percent [CI]: 0.660 [0.555–0.786], P Conclusion Our study suggests that less than fully expanded Sapien 3 THVs are more prone to LT, whereas some degree of waist was protective. These deployment characteristics may help identify patients who qualify for intensified surveillance. Funding Acknowledgement Type of funding source: None

AIMS: The purpose of this registry was to determine the long-term outcomes in patients with asymptomatic contained annulus rupture (CR) as a rare complication of transcatheter aortic valve implantation (TAVI).METHODS AND RESULTS: The ENCORE registry is a multicentre registry (six centres across Europe) of patients with CR diagnosed on post-TAVI computed tomography angiography (CTA) or transoesophageal echocardiography (TEE). A total of 21 patients (mean age 81.9±4.1 years, 81% balloon-expandable TAVI prostheses) were diagnosed with CR (mean size of lesions was 15.3±6.9 × 8.5±3.3 × 8.5±2.3 mm). Seventeen were diagnosed among a total of 1,602 consecutive routine post-TAVI CTA (incidence 1.1%), two in TEE and two in post-TAVI CTA (each conducted due to suspicion of peri-interventional complications). During a mean follow-up of 2.3±1.7 years (cumulative 48.6 patient-years), nine patients (43%) died from non-cardiac causes. None of the patients exhibited symptoms or underwent interventional treatment related to the CR; no sudden cardiac death occurred. A follow-up CTA, performed in eleven patients 240±176 days post TAVI, revealed stable CR findings in seven, regression in one, and remission in three patients.CONCLUSIONS: The results of our international multicentre registry demonstrate favourable long-term outcomes of CR after TAVI supporting a watch-and-wait strategy in these patients.

ObjectiveWe retrospectively analysed outcome data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study to assess the incidence and potential risk factors of sudden cardiac death (SCD) in this prospectively followed cohort of asymptomatic patients with aortic stenosis (AS).MethodsOf the 1873 patients included in SEAS, 1849 (99%) with mild to moderate AS (jet velocity 2.5–4.0 m/s at baseline) and available clinical, echocardiographic and follow-up data were analysed. Patients undergoing aortic valve replacement were censored at the time of operation.ResultsDuring an overall follow-up of 46.1±14.6 months, SCD occurred in 27 asymptomatic patients (1.5%) after a mean of 28.3±16.6 months. The annualised event rate was 0.39%/year. The last follow-up echocardiography prior to the event showed mild to moderate stenosis in 22 and severe stenosis (jet velocity >4 m/s) in 5 victims of SCD. The annualised event rate after the diagnosis of severe stenosis was 0.60%/year compared with 0.46%/year in patients who did not progress to severe stenosis (p=0.79). Patients with SCD were older (p=0.01), had a higher left ventricular mass index (LVMI, p=0.001) and had a lower body mass index (BMI, p=0.02) compared with patients surviving follow-up. Cox regression analysis identified age (HR 1.06, 95% CI 1.01 to 1.11 per year, p=0.02), increased LVMI (HR 1.20, 95% CI 1.10 to 1.32 per 10 g/m2, p2, p=0.01) as independent risk factors of SCD.ConclusionSCD in patients with asymptomatic mild to moderate AS is rare and strongly related to left ventricular hypertrophy but not stenosis severity.

Aims Early leaflet thrombosis (LT) is a well-described phenomenon after transcatheter aortic valve implantation (TAVI) with an incidence around 15%. Data about predictors of LT are scarce. The purpose of the study was to investigate the influence of prosthesis-related factors on the occurrence of LT. Materials and results Fusion imaging of pre- and post-procedural computed tomography angiography was performed in 55 TAVI patients with LT and 140 selected patients as control groups (85 patients in an unmatched and 55 in a matched control) to obtain a 3D reconstruction of the transcatheter heart valve (THV) within the native annulus region. All patients received a balloon-expandable Sapien 3 THV. The THV length above and below the native annulus was measured within the fused images to assess the implantation depth. The deployed THV area was quantified on three heights (left ventricular outflow tract end, stent centre, and aortic end) to determine the average expansion of the prosthesis as percent of the nominal area. We also calculated the extent of prosthesis waist in percent of maximum area. After multivariate adjustment, the extent of THV waist [odds ratio (OR) per 10% (confidence interval, CI) 0.636 (0.526–0.769), P Conclusion Besides the absence of previous oral anticoagulation, a less pronounced waist of the implanted THV was a prosthesis-position-related independent predictor of LT after TAVI using the Sapien 3.

Objectives The aim of this study was to investigate medium-term outcomes in patients with leaflet thrombosis (LT). Background The clinical significance of early LT after transcatheter aortic valve replacement, diagnosed by computed tomography angiography in approximately 10% of patients, is uncertain. Methods In this observational study, computed tomographic angiography was performed a median of 5 days after transcatheter aortic valve replacement and assessed for evidence of LT. Follow-up consisted of clinical visits, telephone contact, or questionnaire. Results LT was diagnosed in 120 of 754 patients (15.9%). Patients with LT were less likely male (36.7% vs. 47.0%, p = 0.045), with a lower rate of atrial fibrillation (28.3% vs. 41.5%, p = 0.008). Peri- and post-procedural characteristics were comparable between groups (e.g., valve implantation technique; p = 0.116). During a median follow-up period of 406 days, there were no significant differences in the primary endpoint of all-cause mortality and the secondary combined endpoint of stroke and transient ischemic attack between patients with LT and those without LT (18-month Kaplan-Meier estimate for mortality 86.6% vs. 85.4%, p = 0.912; for stroke- or transient ischemic attack–free survival 98.5% vs. 96.8%, p = 0.331). In univariate and multivariate analyses, LT was not predictive of either endpoint, whereas male sex (p = 0.03), atrial fibrillation (p = 0.002), and more than mild paravalvular leak (p = 0.015) were associated with all-cause mortality. Conclusions In this prospective observational cohort undergoing post–transcatheter aortic valve replacement computed tomographic angiography, LT was not associated with increased mortality or rates of stroke over a follow-up period of 406 days.

AIM Two-dimensional, transthoracic echocardiography does not account for the noncircular anatomy of the left ventricular outflow tract (LVOT) and may therefore underestimate LVOT area. Fusion of computed tomography (CT)-derived LVOT area and Doppler-derived flow data has been proposed to improve assessment of aortic valve area (AVA) and classification of aortic stenosis severity. For hemodynamic reasons, effective AVA has to be smaller than anatomic AVA. The aim of the study was to test the "fusion approach" by comparing effective CT-derived AVA with anatomic AVA from CT planimetry. METHODS AND RESULTS Data of 244 consecutive patients (mean age 81 ± 5 years, 61% female) with aortic stenosis were retrospectively analyzed comparing effective AVA (calculated from the continuity equation using CT-LVOT and transthoracic Doppler measurements) with anatomic AVA based on CT planimetry. Substituting the LVOT area from transthoracic echocardiography (TTE) by the CT-LVOT resulted in an increase in AVA from 0.74 ± 0.15 to 0.92 ± 0.18cm² (P

Objectives The aim of this study was to investigate whether balloon-expandable and self-expandable transcatheter heart valves (THVs) differ in terms of the incidence of early subclinical leaflet thrombosis (LT). Methods Electrocardiographic-gated cardiac dual-source computed tomography angiography was performed at a median of 5 days after transcatheter aortic valve implantation and assessed for evidence of LT. Results Of the 629 consecutive patients, 538 (86%) received a balloon-expandable THV and 91 (14%) a self-expandable THV. LT was documented in 77 (14%) patients with a balloon-expandable valve and in 16 (18%) with a self-expandable valve (P = 0.42). Similarly, LT was not significantly related to THV size (P = 0.62). Corresponding to a lower rate of atrial fibrillation in the group with LT [25 (27%) vs 222 (41%), P = 0.01], anticoagulation at the time of computed tomography angiography was less frequent in this group [21 (23%) vs 183 (34%), P = 0.03]. Among the other potentially relevant covariables, there was no significant difference in the clinical baseline and the procedural characteristics between patients with and without LT (age 82 ± 6 years vs 82 ± 6 years, P = 0.51; ejection fraction 49 ± 10% vs 50 ± 10%, P = 0.47). In multivariate logistic regression analysis, including potentially relevant covariables, valve type was not significantly associated with LT (P = 0.36). In the univariate and multivariate analyses, only the lack of anticoagulation at the time of computed tomography angiography was predictive of thrombus formation [0.563 (0.335-0.944), P = 0.03; 0.576 (0.343-0.970), P = 0.04]. Conclusions In this large retrospective study of 629 patients, the type and the size of THV was not predictive of early LT.

The number of patients presenting with the combination of atrial fibrillation (AF) and symptoms and signs of heart failure is steadily increasing. Echocardiography as the standard diagnostic tool provides comprehensive information on left ventricular systolic and diastolic function and additional underlying cardiac pathology and has gained a level 1 recommendation in the workup of patients with heart failure.1 However, the scientific basis for this recommendation is weak and—even more worrisome—non-existent, considering practical aspects regarding the assessment of ejection fraction and parameters of diastolic function in patients with AF.2 The suggestion to average a minimum of five beats in an attempt to account for varying cycle length and ventricular filling appears intuitive but whether such an approach delivers reproducible results has very little scientific underpinning, particularly for the assessment of left ventricular ejection fraction.3 Bunting et al , in their article in the current issue of Heart ,4 have to be commended for tackling this knowledge gap by further investigating the ‘index beat’ approach. The index …

Aims The number of pulmonary vein isolation (PVI) ablation procedures is steadily increasing worldwide resulting in a substantial radiation exposure to patients and operators. The aim of our study was to reduce radiation exposure during these procedures to a critical amount without compromising patient safety. Methods and results First, we assessed radiation exposure for primary PVI procedures over time (2005–2015) at the University Heart Center Freiburg-Bad Krozingen. Second, we prospectively evaluated in 52 patients, the efficacy and safety of a novel radiation reduction program (particularly applying an enhanced fluoroscopy pulse dose-reduction and optimized 3D-mapping system use). In 2035 primary PVI procedures, radiation exposure, assessed as estimated effective dose (eED in mSv, dose area product * 0.002 * conversion factor for females), fluoroscopy-time, and procedure-time decreased significantly from 2005 to 2015 (e.g. eED decreased from 9.3 (interquartile range (IQR) 6.4–13.4) mSv to 0.9 (IQR 0.5–1.6) mSv, p for trend

Background An asymptomatic contained rupture (CR) of the aortic annulus is a rare complication of transcatheter aortic valve implantation (TAVI). Their clinical implication is unclear so far. Purpose To determine the long-term outcomes in patients with CR. Methods The ENCORE-registry is a multicenter registry (6 centers across Europe) of patients with CR diagnosed on post-TAVI computed tomography angiography (CTA) or transesophageal echocardiography (TEE). Results A total of 21 patients (mean age 81.9±4.1 years, 81% balloon-expandable TAVI-prostheses) were diagnosed with CR (62% located adjacent to the left coronary cusp, mean size of lesions was 15.3±6.9 x 8.5±3.3 x 8.5±2.3 mm). Seventeen were diagnosed among a total of 1602 consecutive routine post-TAVI CTA (incidence 1.1%), two in TEE and two in post-TAVI CTA (each conducted due to suspicion of periinterventional complications). During a mean follow-up of 2.3±1.7 years nine patients (43%) died from non-cardiac causes. None of the patients exhibited symptoms or underwent interventional treatment related to the CR, no sudden cardiac death occurred. A follow-up CTA, performed in eleven patients 240±176 days post-TAVI, revealed stable CR findings in seven, regression in one, and remission in three patients. Conclusion The results of our ENCORE-registry demonstrate a benign course of initially asymptomatic contained ruptures of the aortic annulus after TAVI supporting a watch-and-wait approach in these patients. Thus, no specific treatment seems to be necessary.

Atrial fibrillation (AF) increases morbidity and mortality in heart failure with preserved ejection fraction (HFpEF), yet identification of HFpEF-patients at risk for new-onset AF is challenging. Amplified P-wave duration (APWD) non-invasively detects arrhythmogenic atrial substrate with high accuracy. We hypothesized that APWD may help in the prediction of new-onset AF in HFpEF.Patients with suspected HFpEF (n = 99, left ventricular ejection fraction 50%, no evidence of valvulopathy, coronary artery disease, or non-cardiac dyspnea) underwent exercise testing with concomitant right-heart catheterization. Normal resting pulmonary capillary wedge pressure (PCWP; 12 mmHg) with an increase during exercise 25.5 mmHg/W/kg defined early HFpEF. Advanced HFpEF was diagnosed with PCWP 12 mmHg at rest. Arrhythmogenic atrial substrate (defined as APWD 150 ms) was investigated on digitized standard 12-lead ECGs and patients were followed for new-onset AF at 6-month intervals.Forty-seven patients had normal exercise haemodynamics and served as controls. Early and advanced HFpEF was diagnosed in 29 and 23 patients, respectively. Eighty-seven per cent of patients with advanced HFpEF had evidence of arrhythmogenic atrial substrate, (APWD 175 ± 29 ms vs. 132 ± 14 ms in controls, p 0.0001), which was associated with a tenfold increased risk for new-onset AF during 4.6 years of follow-up (hazard ratio [HR] 9.684, 95% CI 2.61-35.89, p 0.0001). Early HFpEF was neither related to APWD (p = 0.395), nor to a higher risk for AF (HR 3.44, 95% CI 0.57-20.72, p = 0.178). Importantly, the presence of arrhythmogenic substrate was independent of left atrial indexed volume.The analysis of amplified P-wave duration (APWD) allows for the prediction of new-onset AF in patients with advanced HFpEF.

Objectives This study hypothesized that P-wave morphology and timing under left atrial appendage (LAA) pacing change characteristically immediately upon anterior mitral line (AML) block. Background Perimitral flutter commonly occurs following ablation of atrial fibrillation and can be cured by an AML. However, confirmation of bidirectional block can be challenging, especially in severely fibrotic atria. Methods The study analyzed 129 consecutive patients (66 ± 8 years, 64% men) who developed perimitral flutter after atrial fibrillation ablation. We designed electrocardiography criteria in a retrospective cohort (n = 76) and analyzed them in a validation cohort (n = 53). Results Bidirectional AML block was achieved in 110 (85%) patients. For ablation performed during LAA pacing without flutter (n = 52), we found a characteristic immediate V1 jump (increase in LAA stimulus to P-wave peak interval in lead V1) as a real-time marker of AML block (V1 jump ≥30 ms: sensitivity 95%, specificity 100%, positive predictive value 100%, negative predictive value 88%). As V1 jump is not applicable when block coincides with termination of flutter, absolute V1 delay was used as a criterion applicable in all cases (n = 129) with a delay of 203 ms indicating successful block (sensitivity 92%, specificity 84%, positive predictive value 90%, negative predictive value 87%). Furthermore, an initial negative P-wave portion in the inferior leads was observed, which was attenuated in case of additional cavotricuspid isthmus ablation. Computational P-wave simulations provide mechanistic confirmation of these findings for diverse ablation scenarios (pulmonary vein isolation ± AML ± roof line ± cavotricuspid isthmus ablation). Conclusions V1 jump and V1 delay are novel real-time electrocardiography criteria allowing fast and straightforward assessment of AML block during ablation for perimitral flutter.

Aims Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. Methods and results In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73–0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65–0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64–0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61–0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. Conclusion High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation values.

Background Adjustment of cardiac dimensions by measures of body size appears intuitively convincing and in patients with aortic stenosis, aortic valve area (AVA) is commonly adjusted by body surface area (BSA). However, there is little evidence to support such an approach. Objective To identify the adequate measure of body size for the adjustment of aortic stenosis severity. Methods Parameters of aortic stenosis severity (jet velocity, mean pressure gradient (MPG) and AVA) and measures of body size (height, weight, BSA and body mass index (BMI)) were analysed in 2843 consecutive patients with aortic stenosis (jet velocity >= 2.5 m/s) and related to outcomes in a second cohort of 1525 patients from the Simvastatin/Ezetimibe in Aortic Stenosis (SEAS) study. Results Whereas jet velocity and MPG were independent of body size, AVA was significantly correlated with height, weight, BSA and BMI (Pearson correlation coefficient (r) 0.319, 0.281, 0.317 and 0.126, respectively, all p

We thank Dr. Rashid and colleagues for their interest in our paper. Similar to other studies, recently reviewed by Rashid et al. [(1)][1] in a meta-analysis, the patients in our study were not systematically readmitted for follow-up, and we obtained documentation of the neurological work-up.

Objective To obtain reference values of aortic valve area (AVA) in a large population and to infer the risk of overestimating aortic stenosis (AS) when focusing on flow-corrected indices of severity. Methods We prospectively measured indices of AS in all consecutive echocardiograms performed in a large referral cardiac imaging laboratory for 1 year. We specifically analysed the distribution of AVA, indexed AVA and velocity ratio (Vratio) in patients with and without AS, the latter defined as the coexistence of valvular outflow obstruction (Vmax ≥2.5 m/s) and morphological findings of valve degeneration. Results 16 156 echocardiograms were analysed, 14 669 of which did not show valvular obstruction (peak jet velocity

Atrial Differences in Endothelial Damage, Leukocyte and Platelet Activation Background Thrombi form mainly in the left rather than the right atria of patients with atrial fibrillation (AF), the reason of this predilection being unknown. Objective The purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation, and tissue factor activity occur in patients with AF. Methods Twenty-two patients (16 men, 6 women; age 56 ± 8 years; 16 paroxysmal AF, 6 persistent AF) with AF undergoing pulmonary vein isolation were investigated. Blood samples from the left and the right atrium were obtained at the start of the procedure. Microparticles (MPs) released by apoptotic/stimulated cells were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin were determined (endothelium, platelet, leukocyte). Platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet P-selectin (CD62P), active glycoprotein IIb/IIIa receptor (PAC-1). Platelet aggregation was evaluated using ADP, TRAP and collagen-induced whole blood aggregometry. Results There were no atrial-specific differences in the levels of total procoagulant MPs, leukocyte-derived-MPs or platelet-derived MPs. Conversely, endothelial-derived MPs and tissue factor activity and collagen-induced platelet aggregation were slightly elevated in the right atrium (P < 0.05). Conclusions Our data show no evidence for increased thrombogenic status in the left atrium that would account for its greater propensity for thrombus formation in patients with AF.

Background: We examined whether undetectable levels of high sensitivity cardiac Troponin (hs cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). Methods and results: In a prospective multicenter study we used 4 different hs cTn assays (hs cTnT Roche and hs cTnI Siemens hs cTnI Beckman Coulter and hs cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs cTnT levels 21 had an adjudicated diagnosis of AMI. Among AMI patients 98.2 had initially detectable levels of hs cTnT (sensitivity 98.2 95CI 96.3 99.2 negative predictive value (NPV) 98.6 95CI 97.0 99.3). Undetectable levels of hs cTnT ruled out AMI in 26.5 of patients at presentation. The NPV was similar with the three hs cTnI assays: among 1180 consecutive patients with available hs cTnI (Siemens) the NPV was 98.8; among 1151 consecutive patients with available hs cTnI (Beckman Coulter) the NPV was 99.2; among 1567 consecutive patients with available hs cTnI (Abbott) the NPV was 100.0. The percentage of patients with undetectable levels of hs cTnI was similar among the three hs cTnI assays and ranged from 11.4 to 13.9. Conclusions: Undetectable levels of hs cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs TnT as compared to the investigated hs cTnI assays. © 2013 Elsevier Ireland Ltd. All rights reserved.

Background— Complex-fractionated atrial electrograms and atrial fibrosis are associated with maintenance of persistent atrial fibrillation (AF). We hypothesized that pulmonary vein isolation (PVI) plus ablation of selective atrial low-voltage sites may be more successful than PVI only. Methods and Results— A total of 85 consecutive patients with persistent AF underwent high-density atrial voltage mapping, PVI, and ablation at low-voltage areas (LVA70% of AF cycle length on a single electrode (fractionated activity) or multiple electrodes around the circumferential mapping catheter (rotational activity) or discrete rapid local activity (group I). The procedural end point was AF termination. Arrhythmia freedom was compared with a control group (66 patients) undergoing PVI only (group II). PVI alone was performed in 23 of 85 (27%) patients of group I with low amount (P P =0.42). Conclusions— Ablation of sites with distinct activation characteristics within/at borderzones of LVA in addition to PVI is more effective than conventional PVI-only strategy for persistent AF. PVI only seems to be sufficient to treat patients with left atrial low voltage

Background Experimental data suggest that use of cryoablation in pulmonary vein isolation (PVI) is associated with less cell damage and less thrombus formation compared to radiofrequency (RF) energy. Objective The purpose of this study was to test the hypothesis that cryoablation significantly reduces markers of cell damage, platelet activation, and inflammation in patients undergoing PVI for treatment of atrial fibrillation (AF). Methods Sixty patients with symptomatic drug-resistant AF (age 56 ± 9 years, 48 males, 38 with paroxysmal AF) were randomly assigned to undergo PVI using either an open irrigated-tip RF catheter or a cryoballoon. Markers of cell damage (high-sensitive troponin T [hs-TnT], microparticles), platelet activation (platelet reactivity by aggregometry, expression of platelet surface proteins P-selectin and activated glycoprotein [GP] IIb/IIIa), and inflammatory response (high-sensitive C-reactive protein [hs-CRP]) were determined before and up to 48 hours after the procedure. Results PVI resulted in a significant rise in hs-TnT, microparticles, markers of platelet activation, and hs-CRP over time, with distinct temporal patterns for each parameter. However, after Bonferroni correction for repeated measurements, no significant differences were noted in these parameters between patients treated with cryoablation or RF energy. Procedural time was significantly shorter in patients treated with cryoballoon (177 ± 30 minutes vs 200 ± 46 minutes, P = .03), with no differences in fluoroscopic time, periprocedural complications, or success rate. Conclusion Cryoablation and RF energy result in a comparable rise of markers of cell damage, platelet activation and inflammatory response. The data do not support the concept of an improved safety profile for cryoablation in PVI.

Bioprosthetic valve replacement is the treatment of choice in older patients with symptomatic severe aortic valve disease. Thrombosis of bioprosthetic valves has been considered a rare complication; however, in the presence of valvular obstruction, therapeutic consequences for the individual patient may be dramatic including repeat valve replacement or thrombolysis. We therefore evaluated oral anticoagulation with phenprocoumon as an alternative treatment for obstructive thrombosis of bioprosthetic valves. Six of 470 patients who had received a single stented bioprosthetic aortic valve from January 2007 through December 2008 at our hospital presented with obstructive bioprosthetic valve thrombosis within 14 months postoperatively. All 6 patients (1% of study population) had received a porcine valve (p = 0.1 vs pericardial), were hemodynamically stable, were in sinus rhythm, and were taking acetylsalicylic acid 100 mg/day. Echocardiography showed an increase in mean pressure gradient early postoperatively from 23.3 ± 4 to 57.0 ± 10 mm Hg (p0.001). Five patients were started on phenprocoumon and followed for 114 ± 54 days, when mean pressure gradient had returned to 23.5 ± 6 mm Hg. No adverse events were observed during that period. One patient presenting with dyspnea and fever underwent emergency repeat valve replacement for suspected endocarditis, with histology showing long-term thrombosis of the explanted valve. In conclusion, oral anticoagulation with phenprocoumon represents a safe and effective treatment in clinically stable patients with obstructive thrombosis of bioprosthetic aortic valves, thus obviating repeat valve surgery or thrombolysis.

Pressure-Guided Cryoballoon Pulmonary Vein Isolation.Background: Pulmonary vein (PV) isolation using a balloon-mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Complete PV occlusion during balloon ablation has been shown to predict successful electrical isolation. The aim of this study was to correlate mechanical PV occlusion with changes in a pressure curve recorded at the distal tip of the cryoballoon catheter. Methods and Results: We analyzed 51 PVs in 12 patients (61 ± 6 years old) with paroxysmal AF. At first, PV occlusion via the cryoballoon was documented by changes in the pressure curve. Once the PV is occluded, the pressure curve registered in the vein converts from a left atrial pressure curve to a pulmonary artery pressure curve: the PV wedge curve. Occlusion was then confirmed by transesophageal echocardiography (TEE). Following 2 cryoablation applications, electrical PV isolation was assessed with a circumferential mapping catheter. Under the exclusive guidance of changes in the pressure curve at the tip of the cryoballoon, mechanical occlusion confirmed by TEE was achieved in 47 of 51 PVs (92%). Three PVs required further TEE guidance to achieve occlusion. All 50 occluded veins were electrically isolated after cryoablation. One right inferior vein, which could not be occluded with the balloon, displayed conduction post cryoablation and was isolated by focal ablation. Conclusions: Occlusion and electrical isolation of PVs during cryoballoon ablation can be predicted by the appearance of a PV wedge curve at the tip of the catheter. This new straightforward parameter may facilitate the procedure. (J Cardiovasc Electrophysiol, Vol. 21, pp. 120-125, February 2010)

Background: More extensive ablation strategies for the treatment of atrial fibrillation (AF) have increased success rates but are associated with new and sometimes serious complications. We describe a new complication after extensive radiofrequency (RF) ablation in the left atrium (LA) for persistent AF. Methods and Results: Electroanatomic guided circumferential ablation around both ipsilateral pulmonary veins (PV) was performed with the endpoint of complete conduction block. When necessary, supplementary RF applications were added, including ablation of complex fractionated potentials and/or isolation of other thoracic veins and/or linear left atrial lesions. RF energy was delivered via an irrigated tip catheter with a maximum power of 30–35 W. Four out of 120 patients undergoing extensive RF ablation for persistent AF (including two patients with additional LA substrate modification) developed dyspnea, bilateral pulmonary edema, and signs of a systemic inflammatory response syndrome (SIRS) (rise in body temperature, leukocyte count, and C-reactive protein (CRP levels) 18–48 hours after the procedure. There were no signs of PV stenosis, focal lung injury, left ventricular dysfunction, circulatory failure, or infection. All patients had complete recovery with supportive therapy within 3–4 days after the onset of symptoms. Conclusions: Extensive LA radiofrequency ablation bears the risk of a severe pulmonary edema. Although the precise mechanism is elusive, clinical features point toward a systemic inflammatory response.

The present study tests the consistency of echocardiographic criteria for the grading of aortic valve stenosis.Current guidelines/recommendations define severe stenosis as an aortic valve area (AVA)1 cm2 (or0.6 cm2 adjusted for body surface area), mean pressure gradient (DeltaPm)40 mmHg, or peak flow velocity (Vmax)4 m/s. We tested the consistency of the three criteria for the grading of aortic valve stenosis in 3483 echocardiography studies performed in 2427 patients with normal left ventricular (LV) systolic function and a calculated AVA ofor =2 cm2. We calculated curve fits for the relationship between AVA and DeltaPm using the Gorlin equation and between AVA and Vmax based on the continuity equation for our study population. An AVA of 1.0 cm2 correlated to a DeltaPm of 21 mmHg and a Vmax of 3.3 m/s. Conversely, a DeltaPm of 40 mmHg corresponds to an AVA of 0.75 cm2 and a Vmax of 4.0 m/s to an AVA of 0.82 cm2. Consequently, severe stenosis was diagnosed in 69% of patients based on AVA, 45% on Vmax, and 40% on DeltaPm. Stroke volume was lower in inconsistently graded patients (65 +/- 11 mL vs. consistently graded: 70 +/- 14 mL, P0.001).The criteria for the grading of aortic stenosis are inconsistent in patients with normal systolic LV function. On the basis of AVA, a higher proportion of patients is classified as having severe aortic valve stenosis compared with mean pressure gradient and peak flow velocity. Discrepant grading in these patients may be partly due to reduced stroke volume.

Obstructive thrombosis of bioprosthetic valves is considered rare but may have dramatic consequences for the individual patient including repeat valve replacement, thrombolysis, or long-term anticoagulation. Whether the risk of obstructive thrombosis is dependent on the type of bioprosthesis (porcine versus bovine pericardial) is uncertain.Between 2007 and 2012 a total of 1751 patients received a single stented bioprosthesis in the aortic valve position, 749 (43%) were porcine and 1002 (57%) bovine. During a mean follow-up of 3.4±1.9years, obstructive thrombosis (identified by an increase in mean pressure gradient≥20mm Hg or a decrease in velocity ratio≥0.05 and confirmed by either ECG-gated computer tomography, a return to baseline of stenosis parameters under treatment with a vitamin K antagonist, or histology in case of reoperation) was diagnosed in 17 patients with a porcine (2.3%) and none with a bovine valve (p0.001). The cumulative probability of developing an obstructive thrombosis was significantly higher in patients with a porcine valve (p0.001 log-rank test). Adjusting for differences in baseline variables and stratification by the estimated propensity score showed that strata with a high probability of receiving a bovine valve had the highest number of obstructive thrombosis in porcine valves. These findings were further confirmed in a Poisson model and a competing risk model including all-cause mortality. Treatment of obstructive thrombosis with a vitamin K antagonist was safe and effective in 15/17 patients.The porcine valve type is an independent predictor of obstructive thrombosis in bioprostheses in the aortic position.

To evaluate the usefulness of velocity ratio (VR) in patients with low gradient severe aortic stenosis (LGSAS) and preserved EF.LGSAS despite preserved EF represents a clinically challenging entity. Reliance on mean pressure gradient (MPG) may underestimate stenosis severity as has been reported in the context of paradoxical low flow, LGSAS. On the other hand, grading of stenosis severity by aortic valve area (AVA) may overrate stenosis severity due to erroneous underestimation of LV outflow tract (LVOT) diameter, small body size or inconsistencies in cut-off values for severe stenosis. We hypothesised that VR may have conceptual advantages over MPG and AVA, predict clinical outcomes and thereby be useful in the management of patients with LGSAS.Patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study with an AVA1.0 cm(2), MPG≤40 mm Hg and EF≥55% and asymptomatic at baseline were stratified according to VR with a cut-off value of 0.25. Outcomes were evaluated according to aortic valve-related events and cardiovascular death.Of 435 patients with LGSAS, 197 (45%) had VR0.25 suggesting severe and 238 (55%) had VR≥0.25 suggesting non-severe stenosis. Aortic valve-related events (mean follow-up 42±14 months) were more frequent in patients with VR0.25 (57% vs 41%; p0.001) as was cardiovascular death within the first 24 months (p0.05). In multivariable Cox regression analysis, MPG was the strongest independent predictor of aortic valve events (p0.001) followed by VR (p0.02). Adjusting AVA by VR increased predictive accuracy for aortic valve events (area under the receiver operating curve 0.62 (95% CI 0.57 to 0.67) vs 0.56 (95% CI 0.51 to 0.61) for AVA, p=0.02) with net reclassification improvement calculated at 0.36 (95% CI 0.17 to 0.54, p0.001). VR did not improve the prediction of clinical events by MPG.In the difficult setting of LGSAS, VR shows a strong association with valve-related events and-although not outperforming MPG-may be particularly useful in guiding clinical management.NCT00092677.

Increased life expectancy has led to a higher prevalence of calcific aortic valve disease. Both ends of the disease spectrum-sclerosis of the aortic valve without hemodynamic obstruction and the late stage of aortic valve stenosis (AS)-have been associated with increased morbidity and mortality. This raises the question of the prognostic contribution of atherosclerotic diseases and other comorbidities as opposed to the hemodynamic effect of obstructive AS. Hence, the evaluation of asymptomatic patients with mild or moderate AS without comorbidities is of major interest. In the Simvastatin and Ezetimibe in Aortic Stenosis study, with the exception of hypertension, comorbidities were excluded, thus allowing an analysis of the effect of pure AS as well as the effect of hypertension on the progression and outcome of AS. We discuss the results that emerged from this large European prospective study and relate these to the published literature.

BACKGROUND Current guidelines require a change (rise and/or fall) in levels of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI). It is unknown whether absolute or relative changes provide higher accuracy when using high sensitivity cTnI assays. METHODS In a prospective international multicentre study we assessed the diagnostic accuracy of early absolute and relative changes in cTnI measured with two novel pre commercial high sensitivity assays (Siemens and Beckman Coulter) in 943 unselected patients presenting to the ED with suspected AMI. The final diagnosis of AMI was adjudicated using all available data including serial hs cTnT levels by two independent cardiologists. RESULTS The diagnostic accuracy of absolute changes in the diagnosis of AMI as quantified by the area under the receiver operating characteristics curve (AUC) was very high (e.g. at 2h Siemens high sensitivity cTnI AUC 0.93 95Cl 0.90 0.96; Beckman Coulter high sensitivity cTnI AUC 0.93 95Cl 0.90 0.96) and superior to relative changes at all time points (p

Background Smoking is a primary risk factor for coronary and peripheral vascular disease. Because the endothelium is a principal target for the effects of risk factors early in the pathogenesis of atherosclerosis, we investigated whether long-term smoking is associated with impaired endothelial vasodilator function of epicardial conductance vessels regardless of the presence or absence of atherosclerotic lesions. Methods and Results Using quantitative coronary angiography, we measured epicardial artery diameter at baseline, after maximal increases in coronary blood flow that caused flow-mediated dilation (which is strictly endothelium dependent), and after intracoronary injection of nitroglycerin (an endothelium-independent dilator) in 96 patients. Endothelium-dependent, flow-mediated dilation was significantly ( P P P P r =−.82, P P Conclusions Long-term cigarette smoking is associated with impaired endothelium-dependent coronary vasodilation regardless of the presence or absence of coronary atherosclerotic lesions.

Aims In aortic valve stenosis (AS), having a small aortic root may influence both the assessment of AS severity and the treatment strategy. The aim was to test the prognostic implications of having a small aortic root in AS within a large prospective study. Methods and results We used data from 4.3-year follow-up of 1560 patients with asymptomatic, initially mostly moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. A small aortic root was defined as inner aortic sinotubular junction diameter indexed for body height

Response to Letters Regarding Article, "Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction"

Background— Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area 2 and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient “severe” stenosis (defined as aortic valve area 2 and mean gradient ≤40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Methods and Results— Outcome in patients with low-gradient “severe” aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm 2 ; mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67±10 years; ejection fraction, ≥55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182±64 versus 212±68 g; P P =0.37; major cardiovascular events, 50.9% versus 48.5%, P =0.58; cardiovascular death, 7.8% versus 4.9%, P =0.19). Low-gradient severe stenosis patients with reduced stroke volume index (≤35 mL/m 2 ; n=223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P =0.53). Conclusions— Patients with low-gradient “severe” aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.

On echocardiography approximately one-third of patients with severe aortic valve stenosis based on aortic valve area (AVA1.0 cm(2)) demonstrate a non-severe mean pressure gradient (DeltaPm;or =40 mm Hg) despite apparently normal left ventricular function. It has been suggested that inconsistent echocardiographic grading may be due to 'paradoxical' low stroke volume. However, the correct echocardiographic assessment of stroke volume hinges on the often problematic measurement of the left ventricular outflow tract (LVOT) diameter.To investigate whether inconsistent grading and reduced stroke volume persist when the quantification of aortic valve stenosis is based on cardiac catheterisation which is independent of LVOT measurements.333 consecutive patients underwent cardiac catheterisation within 30 days after their index echocardiography showing an AVAor =2 cm(2) and shortening fractionor =30%. On invasive testing 85 patients (26%) demonstrated inconsistent (AVA1 cm(2) and DeltaPmor =40 mm Hg) and 153 (46%) consistent grading (AVA1 cm(2) and DeltaPm40 mm Hg) with the remainder (28%) presenting with a calculated AVAor =1 cm(2). Inconsistently graded patients were older (71 vs 67 years, p0.006) with no differences in sex or body surface area between groups. Stroke volume and stroke volume index were significantly lower in inconsistently graded patients (63+/-14 vs 73+/-18 ml and 35+/-7 vs 39+/-7 ml/m(2), respectively, both p0.001). However, 41/85 (48%) of inconsistently graded patients had a normal stroke volume index35 ml/m(2).In the framework of current guidelines inconsistent grading of aortic valve stenosis is common, extends to cardiac catheterisation and is only partially explained by low stroke volume despite apparently normal left ventricular systolic function.