5-Year outcomes after transcatheter aortic valve implantation: Focus on paravalvular leakage assessed by echocardiography and hemodynamic parameters.

OBJECTIVES: We sought to assess the impact of echocardiographic and hemodynamic grading of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) on the prediction of 5-year mortality. PVL after TAVI is known to influence outcome after TAVI. Yet, present available data of long-term outcomes and especially the comparison of different modalities for measurement of PVL is little. METHODS: We performed a retrospective single-center cohort study and compared the prognostic value of echocardiographic PVL grading as well as the aortic regurgitation index (ARI) pre- and post-TAVI. Univariable and multivariable Cox proportional regression analysis generated hazard ratios for mortality. RESULTS: A total of 464 patients underwent TAVI at our center between August 2012 and Decemebr 2014, with self-expandable CoreValve (11%) or balloon-expandable Sapien XT (47.4%) and Sapien 3 (41.6) valves. Overall 5-year mortality was 52.4% (243/464). Echocardiographic classes of PVL at discharge showed a significant (p = 0.002) association with 5-year mortality, mild PVL remained as an independent predictor for 5-year mortality in multivariable analysis (hazard ratio: 1.642 [95% confidence interval: 1.235-2.182]; p = 0.001). Grades of PVL as assessed during the procedure by ARI (below the previously defined cut-off of 25) did not show a significant association with 5-year mortality (p = 0.417 and p = 0.995, respectively). CONCLUSIONS: Even mild PVL assessed by echocardiography was an independent predictor for 5-year survival, whereas hemodynamic measurements did not help to identify PVLs that are relevant to 5-year survival.

Impact of high-sensitivity cardiac troponin T on survival and rehospitalization after transcatheter aortic valve replacement.

BACKGROUND: Constant elevations of the serum concentration of cardiac troponin T (TnT) indicate a myocardial injury that may affect the long-term outcome of transcatheter aortic valve replacement (TAVR). OBJECTIVES: We sought to investigate the impact of pre-TAVR TnT on outcomes after TAVR during long-term follow-up. METHODS: In a retrospective, observational study we compared long term outcomes after TAVR between tertiles of preinterventional high-sensitivity TnT. Systematic follow-up was performed annually for 5 years. The primary endpoint was a composite of all-cause death and any rehospitalization. RESULTS: Between 2010 and 2018, 2,129 patients with severe aortic valve stenosis underwent TAVR at our institution (mean age 82.6 years, 57.2% female, logistic EuroSCORE 20.5 ± 15.8). Boundaries for TnT tertiles were <21 ng/L and >42 ng/L. The median follow-up was 895 days. Three-year incidences for the primary endpoint were 70.9%, 76.6%, and 81.7% in the low, middle, and high tertile (log rank p < .001). Compared with the first tertile, the corresponding adjusted hazard ratios were 1.23 (95%-CI 1.08-1.40, p < .001) and 1.50 (95%-CI 1.32-1.70, p < .001) for the second and third tertile. We found consistent differences between TnT strata for all-cause death (3-year incidences 23.3%, 33.3%, and 47.1%; adjusted p < .001) and rehospitalization (3-year incidences 64.7%, 68.7% and 72.0%; adjusted p < .001), including significant differences in deaths (p < .001). The association between TnT and outcome was independent of coronary artery disease or low aortic valve gradient. CONCLUSIONS: TnT before TAVR is strongly associated with all-cause death and rehospitalization during 3-year follow-up.

Non-invasive body surface electrocardiographic imaging for diagnosis of atrial cardiomyopathy.

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 < 0.0001 respectively). Atrial cardiomyopathy was found in 23 (59%) patients. A TACT value of 148 ms identified ACM with 91.3% sensitivity and 93.7% specificity. Arrhythmia recurrence occurred in 15 (38%) patients during a follow-up of 389 ± 55 days. Freedom from arrhythmia was significantly higher in patients with a TACT <148 ms compared with patients with a TACT ≥148 ms (82.4% vs. 45.5%, P = 0.019). 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.

Perioperative Changes of Right Ventricular Function in Cardiac Surgical Patients Assessed by Myocardial Deformation Analysis and 3-Dimensional Echocardiography.

OBJECTIVES: To test the hypothesis that longitudinal strain of the right ventricle (RV) is significantly reduced in patients undergoing cardiac surgery with extracorporeal circulation and cardioplegic cardiac arrest at the end of surgery, whereas RV ejection fraction remains unchanged. DESIGN: Prospective observational cohort study. SETTING: Single university hospital. PARTICIPANTS: Thirty patients with normal myocardial function undergoing coronary artery bypass grafting with cardioplegic cardiac arrest. INTERVENTIONS: Right ventricular 3-dimensional echocardiography and strain analysis were performed preoperatively, intraoperatively, and postoperatively. MEASUREMENTS AND MAIN RESULTS: Peak longitudinal systolic strain of the RV lateral and inferior wall, RV outflow tract, and interventricular septum was reduced significantly at the end of surgery after sternal closure compared to preoperatively (lateral: -16 ± 5 v -22 ± 4, p < 0.001; inferior: -12 ± 4 v -19 ± 5, p < 0.001; outflow tract, -11 ± 5 v . -20 ± 6, p < 0.001; septum: -9 ± 3 v -14 ± 4, p < 0.001), whereas peak circumferential systolic strain of the RV lateral wall had increased significantly (-16 ± 4 v -12 ± 5, p = 0.008). Right ventricular ejection fraction remained stable (51 ± 6% v. 50 ± 7%, p = 0.34). CONCLUSION: In patients undergoing coronary artery bypass grafting with cardioplegic cardiac arrest, the longitudinal contraction of the RV lateral and inferior wall, the RV outflow tract, and the interventricular septum is impaired at the end of surgery. This impairment is compensated by an increase in circumferential contraction without changes in RV ejection fraction.

Rapid improvement in left ventricular function after sinus rhythm restoration in patients with idiopathic cardiomyopathy and atrial fibrillation.

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 < 0.001) as quantified by echocardiography. Comparable results were obtained using cMRI (baseline: 29 ± 8%; Day 3: 42 ± 9%). Three patients showed no response to SRR (EF improvement <15%). The percentage of patients meeting current criteria for implantable cardioverter-defibrillator (ICD) implantation for primary prevention dropped from 76% (n = 38) to 11% (n = 3) on Day 40 following SRR. No specific clinical or echocardiographic factor predicting improved EF after SRR could be identified. CONCLUSION: The majority of patients presenting with non-ischaemic, non-valvular heart failure with reduced EF and concomitant AF show a significant and rapid improvement in EF following SRR. An attempt at SRR and reassessment of the need for ICD implantation after 40 days may be warranted in all such patients.

Hemodynamic classification of paravalvular leakage after transcatheter aortic valve implantation compared with angiographic or echocardiographic classification for prediction of 1-year mortality.

OBJECTIVES: We sought to assess angiographic, echocardiographic and hemodynamic grading of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) with respect to prediction of 1-year mortality. BACKGROUND: Meaningful criteria for the severity of PVL are needed to allow intraprocedural guidance and patient management after TAVI. METHODS: We pooled the prospective TAVI databases of 2 German centers. During TAVI, PVL was assessed angiographically and by the aortic regurgitation index (ARI). ARI was calculated as ratio of the gradient between diastolic blood pressure and left ventricular end-diastolic pressure to systolic blood pressure times hundred. In addition, we performed transthoracic echocardiography before discharge. RESULTS: A total of 723 patients undergoing TAVI with self-expandable (20.9%) or balloon-expandable (79.1%) valves were included. Grades of PVL as assessed during the procedure by angiography or ARI (below the previously defined cut-off of 25) did not show a significant association with 1-year mortality (P = 0.312 and 0.776, respectively). One-year mortality was 15.7% (39/249) in patienths with an ARI < 25 and 16.5% (71/430) in patients with an ARI ≥ 25. Echocardiographic classes of PVL at discharge showed a significant (P = 0.029) association with 1-year mortality, which was 11.5% (37/322) in patients with no/trace PVL, 18.0% (62/345) in patients with mild PVL and 23.1% (6/26) in patients with more than mild PVL. These findings prevailed after multivariable adjustment. CONCLUSIONS: ARI did not help identify PVLs that are relevant to 1-year survival. Angiographic assessment during the procedure was less predictive than echocardiographic assessment before discharge.

Anatomic estimation of aortic stenosis severity vs "fusion" of data from computed tomography and Doppler echocardiography.

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 < .01), which was larger than anatomic AVA (0.82 ± 0.15cm²). Similar results were obtained based on planimetry from transesophageal echocardiography (TEE; AVA 0.79 ± 0.14cm², P < .01 vs CT-LVOT) and in the subgroup presenting with low-gradient severe aortic stenosis and preserved ejection fraction (n = 67, AVA from TTE 0.76 ± 0.09; from CT-LVOT 0.97 ± 0.14; CT planimetry 0.86 ± 0.12; TEE planimetry 0.82 ± 0.13cm²). CONCLUSION: Fusion of CT-derived LVOT area with Doppler echocardiography results in a calculated effective AVA that is larger than the corresponding anatomic AVA. Therefore, adjustment of partition values may be warranted when using this approach.

Early hypo-attenuated leaflet thickening in balloon-expandable transcatheter aortic heart valves.

AIMS: We sought to evaluate the frequency of early hypo-attenuated leaflet thickening (HALT) of the SAPIEN 3 transcatheter aortic valve (S3). METHODS AND RESULTS: Of 249 patients who had undergone S3 implantation, we studied 156 consecutive patients (85 women, median age 82.2 ± 5.5 years) by electrocardiogram (ECG)-triggered dual-source computed tomography angiography (CTA) after a median of 5 days post-transcatheter aortic valve implantation. The prosthesis was assessed for HALT. Apart from heparin, peri-interventional antithrombotic therapy consisted of single- (aspirin 29%) or dual- (aspirin plus clopidogrel 71%) antiplatelet therapy. Hypo-attenuated leaflet thickening was found in 16 patients [10.3% (95% confidence interval (CI) 5.5-15.0%)] of the patients. None of the baseline and procedural variables were significantly associated with HALT, nor did we find a significant association with the antithrombotic regimen, either peri-interventionally or at the time of CTA. Hypo-attenuated leaflet thickening was found in 6 of 45 patients with peri-interventional single-antiplatelet therapy and in 10 of 111 patients with dual-antiplatelet therapy at the time of intervention [13.3% (95% CI 3.4-23.3%) vs. 9% (95% CI 3.7-14.3%), P = 0.42]. Hypo-attenuated leaflet thickening was not associated with clinical symptoms, but a small, albeit significant difference in mean pressure gradient at the time of CTA (11.6 ± 3.4 vs. 14.9 ± 5.3 mmHg, P = 0.026). Full anticoagulation led to almost complete resolution of HALT in 13 patients with follow-up CTA. CONCLUSION: Irrespective of the antiplatelet regimen, early HALT occurred in 10% of our patients undergoing transcatheter aortic S3 implantation. Early HALT is clinically inapparent and reversible by full anticoagulation.

Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction.

AIMS: In patients with suspected heart failure with preserved ejection fraction (HFpEF), invasive exercise testing may be considered when measurements at rest are inconclusive. However, the prognostic impact of invasive exercise testing is uncertain, so far. METHODS AND RESULTS: We retrospectively analysed mortality in 355 patients [mean age 61.2 ± 11.3 years, 235 (66.2%) women] with unexplained dyspnoea and suspected HFpEF. During an invasive haemodynamic stress test pulmonary capillary wedge pressure (PCWP) at rest and the PCWP response to exercise, expressed as the ratio of PCWP at peak exercise to workload normalized to body weight [PCWL (mmHg/W/kg)], were recorded. Both PCWP at rest and PCWL were significant and independent predictors of long-term mortality. Adding PCWL to PCWP at rest improved reclassification of patients into survivors or non-survivors with a net reclassification improvement (NRI) of 0.56 (95% CI: 0.29-0.83; P < 0.001). Ten-year mortality was 6.6% in subjects with low PCWP at rest (≤ 12 mmHg) and low PCWL (≤ 25.5 mmHg/W/kg); 28.2% in patients with low PCWP and high PCWL and 35.2% in those with high PCWP and high PCWL. Compared with patients with low PCWP and low PCWL, the adjusted hazard ratio for mortality was 2.37 (95% CI: 1.09-5.17; P = 0.029) for the low-PCWP/high-PCWL group and 4.75 (95% CI: 1.90-11.84; P < 0.001) for patients with high PCWP/high PCWL. CONCLUSION: In patients with suspected HFpEF, invasive exercise testing substantially improves prediction of long-term mortality. An excessive rise of PCWP during exercise despite normal PCWP at rest is associated with increased mortality and may be considered as early HFpEF.

Quantification of Aortic Valve Calcification in Contrast-Enhanced Computed Tomography.

Background: The goal of our study is to evaluate a method to quantify aortic valve calcification (AVC) in contrast-enhanced computed tomography for patients with suspected severe aortic stenosis pre-interventionally. Methods: A total of sixty-five patients with aortic stenosis underwent both a native and a contrast-enhanced computed tomography (CECT) scan of the aortic valve (45 in the training cohort and 20 in the validation cohort) using a standardized protocol. Aortic valve calcification was semi-automatically quantified via the Agatston score method for the native scans and was used as a reference. For contrast-enhanced computed tomography, a calcium threshold of the Hounsfield units of the aorta plus four times the standard deviation was used. Results: For the quantification of aortic valve calcification in contrast-enhanced computed tomography, a conversion formula (691 + 1.83 x AVCCECT) was derived via a linear regression model in the training cohort. The validation in the second cohort showed high agreement for this conversion formula with no significant proportional bias (Bland-Altman, p = 0.055) and with an intraclass correlation coefficient in the validation cohort of 0.915 (confidence interval 95% 0.786-0.966) p < 0.001. Conclusions: Calcium scoring in patients with aortic valve stenosis can be performed using contrast-enhanced computed tomography with high validity. Using a conversion factor led to an excellent agreement, thereby obviating an additional native computed tomography scan. This might contribute to a decrease in radiation exposure.

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 < 1.0 cm² 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 < 1.0 cm² 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 cm²; 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 < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (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/m²; 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.

Pulmonary Capillary Wedge Pressure during Exercise Is Prognostic for Long-Term Survival in Patients with Symptomatic Heart Failure.

Aims: Exercise stress testing can stratify specific populations of heart failure patients for mortality risk, but is not universally applied. The aim of the present study was to investigate the prognostic capabilities of invasive exercise testing in a real-world cohort of suspected heart failure patients in whom non-cardiac causes of dyspnea were excluded. Methods: We retrospectively analyzed the survival of 682 patients who underwent right heart catheterization at rest and during exercise between 2007 and 2017 for dyspnea and expected heart failure. Pulmonary capillary wedge pressure (PCWP) at rest and the PCWP response to exercise, expressed as the ratio of PCWP at peak exercise to workload normalized to body weight (PCWL (mmHg/W/kg)), were determined. Mortality data were retrieved from the official German death registry. Results: Over a median follow-up period of 8.5 years, PCWL is a stronger predictor of all-cause mortality than PCWP. Patients featuring a reduced left ventricular ejection fraction (LVEF; <50%), but favorable response to exercise (PCWL <34.7 mmHg/W/kg), have a similar mortality risk to patients with a normal LVEF and low PCWL (hazard ratio (HR) 1.180, 95% CI 0.48−2.91, p = 0.719). Irrespective of LVEF, an increased PCWL during exercise was associated with a significantly increased mortality (HR 1.950 with preserved LVEF, 95% CI 1.12−3.34, p = 0.018; and HR 3.212 with impaired LVEF, 95% CI 1.75−5.70, p < 0.001). Conclusions: In patients with clinical heart failure, invasive exercise testing improves the prediction of mortality. Subjects with a favorable response to exercise have a relatively low mortality irrespective of left ventricular systolic function.

Prognostic impact of invasive exercise haemodynamics in patients with severe mitral regurgitation.

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 < 0.001], whereas systolic pulmonary artery pressure and current guideline criteria were not. Adding maximum pulmonary capillary wedge pressure >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.

Electrocardiographic diagnosis of atrial cardiomyopathy to predict atrial contractile dysfunction, thrombogenesis and adverse cardiovascular outcomes.

Thromboembolism and stroke are dreaded complications in atrial fibrillation (AF). Established risk stratification models identify susceptible patients, but their discriminative properties are poor. Atrial cardiomyopathy (ACM) is associated to thromboembolism and stroke in smaller studies, but the modalities used for ACM-diagnosis (MRI and endocardial mapping) are unsuitable for widespread population screening. We aimed to investigate an ECG-based diagnosis of ACM using amplified p-wave analysis (APWA) for stratification of thromboembolic risk and cardiovascular outcome. In this case-control study, ACM-staging was performed using APWA on digital 12-lead sinus rhythm-ECGs in patients with LAA-thrombus and a propensity-score-matched control-cohort. Left atrial contractile function and thrombi were evaluated by transesophageal echocardiography (TEE). Outcome for MACCE including death was assessed using official registries and structured phone interviews. Left-atrial appendage [LAA]-thrombi and appropriate sinus rhythm-ECGs for ACM-staging were found in 109 of 4086 patients that were matched 1:1 to control patients without thrombus (218 patients in total). Both cohorts were comparable regarding cardiovascular risk factors, anticoagulants and CHA2DS2-VASC-score. ACM-stages 1 to 3 (equivalent to no, moderate and extensive ACM) were found in 63 (57.8%), 36 (33.0%) and 10 (9.2%) of patients without and 3 (2.8%), 23 (21.1%) and 83 (76.1%) of patients with LAA-thrombi. Atrial contractile function decreased from ACM-stages 1 to 3 (LAA-flow velocities 38 ± 16 cm/s, 31 ± 15 cm/s and 21 ± 12 cm/s; p < 0.0001), while the likelihood for LAA-thrombus increased (2.8%, 21.1% and 76.1%, p < 0.001). Multivariable analysis confirmed an independent odds ratio for LAA-thrombus of 24.6 (p < 0.001) per ACM-stage. Two-year survival free of stroke/TIA, hospitalization for heart failure, myocardial infarction or all-cause death was strongly reduced in ACM-stage 3 (53.8%) compared to no or moderate ACM (82.8% and 84.7%, respectively; p < 0.0001). Electrocardiographic diagnosis of ACM identifies patients with atrial contractile dysfunction and atrial thrombi at risk for adverse cardiovascular outcomes and death.

Echocardiographic and Electrocardiographic Determinants of Atrial Cardiomyopathy Identify Patients with Atrial Fibrillation at Risk for Left Atrial Thrombogenesis.

Objective: Atrial cardiomyopathy (ACM) is associated with development of AF, left atrial (LA) thrombogenesis, and stroke. Diagnosis of ACM is feasible using both echocardiographic LA strain imaging and measurement of the amplified p-wave duration (APWD) in digital 12-lead-ECG. We sought to determine the thresholds of LA global longitudinal strain (LA-GLS) and APWD that identify patients with AF at risk for LA appendage (LAA) thrombogenesis. Methods: One hundred and twenty-eight patients with a history of AF were included. Left atrial appendage maximal flow velocity (LAA-Vel, in TEE), LA-GLS (TTE), and APWD (digital 12-lead-ECG) were measured in all patients. ROC analysis was performed for each method to determine the thresholds for LA-GLS and the APWD, enabling diagnosis of patients with LAA-thrombus. Results: Significant differences in LA-GLS were found during both rhythms (SR and AF) between the thrombus group and control group: LA-GLS in SR: 14.3 ± 7.4% vs. 24.6 ± 9.0%, p < 0.001 and in AF: 11.4 ± 4.2% vs. 16.1 ± 5.0%, p = 0.045. ROC analysis revealed a threshold of 17.45% for the entire cohort (AUC 0.82, sensitivity: 84.6%, specificity: 63.6%, Negative Predictive Value (NPV): 94.3%) with additional rhythm-specific thresholds: 19.1% in SR and 13.9% in AF, and a threshold of 165 ms for APWD (AUC 0.90, sensitivity: 88.5%, specificity: 75.5%, NPV: 96.2%) as optimal discriminators of LAA-thrombus. Moreover, both LA-GLS and APWD correlated well with the established contractile LA-parameter LAA-Vel in TEE (r = 0.39, p < 0.001 and r = −0.39, p < 0.001, respectively). Conclusion: LA-GLS and APWD are valuable diagnostic predictors of left atrial thrombogenesis in patients with AF.

Echocardiographic diagnosis of atrial cardiomyopathy allows outcome prediction following pulmonary vein isolation.

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 < 34% predicted ACM with an area under the curve (AUC) of 0.846 (sensitivity 69.2%, specificity 76.5%) similar to a LASr < 23.5% (AUC 0.878, sensitivity 92.3%, specificity 82.4%). In the validation cohort, these cut-offs established the correct diagnosis of ACM in 76% of patients (positive predictive values 87%/93% and negative predictive values 73%/75%, respectively). Arrhythmia recurrence in the entire cohort was significantly more frequent in patients with LA-EF < 34% and LASr < 23.5% (56% vs. 29% and 55% vs. 26%, both p < 0.05). CONCLUSION: The echocardiographic parameters LA-EF and LAS allow accurate, non-invasive diagnosis of ACM and prediction of arrhythmia recurrence after PVI.

Left Atrial Hypertension, Electrical Conduction Slowing, and Mechanical Dysfunction - The Pathophysiological Triad in Atrial Fibrillation-Associated Atrial Cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and a significant burden for healthcare systems worldwide. Presence of relevant atrial cardiomyopathy (ACM) is related to persistent AF and increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). OBJECTIVE: To investigate the association of left atrial pressure (LAP), left atrial electrical [invasive atrial activation time (IAAT) and amplified p-wave duration (aPWD)] and mechanical [left atrial emptying fraction (LA-EF) and left atrial strain (LAS)] functional parameters with the extent of ACM and their impact on arrhythmia recurrence following PVI. MATERIALS AND METHODS: Fifty patients [age 67 (IQR: 61-75) years, 78% male] undergoing their first PVI for persistent AF were prospectively included. LAP (maximum amplitude of the v-wave), digital 12-lead electrocardiogram, echocardiography and high-density endocardial contact mapping were acquired in sinus rhythm prior to PVI. Arrhythmia recurrence was assessed using 72-hour Holter electrocardiogram at 6 and 12 months post PVI. RESULTS: Relevant ACM (defined as left atrial low-voltage extent ≥2 cm2 at <0.5 mV threshold) was diagnosed in 25/50 (50%) patients. Compared to patients without ACM, patients with ACM had higher LAP [17.6 (10.6-19.5) mmHg with ACM versus 11.3 (7.9-14.0) mmHg without ACM (p = 0.009)]. The corresponding values for the electrical parameters were 166 (149-181) ms versus 139 (131-143) ms for IAAT (p < 0.0001), 163 (154-176) ms versus 148 (136-152) ms for aPWD on surface-ECG (p < 0.0001) and for the mechanical parameters 27.0 (17.5-37.0) % versus 41.0 (35.0-45.0) % for LA-EF in standard 2D-echocardiography (p < 0.0001) and 15.2 (11.0-21.2) % versus 29.4 (24.9-36.6) % for LAS during reservoir phase (p < 0.0001). Furthermore, all parameters showed a linear correlation with ACM extent (p < 0.05 for all). Receiver-operator-curve-analysis demonstrated a LAP ≥12.4 mmHg [area under the curve (AUC): 0.717, sensitivity: 72%, and specificity: 60%], a prolonged IAAT ≥143 ms (AUC: 0.899, sensitivity: 84%, and specificity: 80%), a prolonged aPWD ≥153 ms (AUC: 0.860, sensitivity: 80%, and specificity: 79%), an impaired LA-EF ≤33% (AUC: 0.869, sensitivity: 84%, and specificity: 72%), and an impaired LAS during reservoir phase ≤23% (AUC: 0.884, sensitivity: 84%, and specificity: 84%) as predictors for relevant ACM. Arrhythmia recurrence within 12 months post PVI was significantly increased in patients with relevant ACM ≥2 cm2, electrical dysfunction with prolonged IAAT ≥143 ms and mechanical dysfunction with impaired LA-EF ≤33% (66 versus 20, 50 versus 23 and 55 versus 25%, all p < 0.05). CONCLUSION: Left atrial hypertension, electrical conduction slowing and mechanical dysfunction are associated with ACM. These findings improve the understanding of ACM pathophysiology and may be suitable for risk stratification for new-onset AF, arrhythmia recurrence following PVI, and development of novel therapeutic strategies to prevent AF and its associated complications.

Pressure-guided cryoballoon isolation of the pulmonary veins for the treatment of paroxysmal atrial fibrillation.

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.

Sudden cardiac death in asymptomatic patients with aortic stenosis.

OBJECTIVE: We 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). METHODS: Of 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. RESULTS: During 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, p<0.001) and lower BMI (HR 0.87, 95% CI 0.79 to 0.97 per kg/m2, p=0.01) as independent risk factors of SCD. CONCLUSION: SCD in patients with asymptomatic mild to moderate AS is rare and strongly related to left ventricular hypertrophy but not stenosis severity.

Cryoballoon pulmonary vein isolation guided by transesophageal echocardiography: novel aspects on an emerging ablation technique.

BACKGROUND: Pulmonary vein (PV) isolation using a balloon-mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Transesophageal echocardiography (TEE) allows real-time visualization of cryoballoon positioning and successful vein occlusion via color Doppler. We hypothesized that PV mechanical occlusion monitored with TEE could predict effective electrical isolation. METHODS: We studied 124 PVs in 30 patients. Under continuous TEE assessment, a cryoballoon was placed in the antrum of each PV aiming for complete PV occlusion as documented by color Doppler. At the end of the procedure, PV electrical isolation was evaluated using a circumferential mapping catheter. RESULTS: Of the 124 PVs studied, 123 (99.2%) could be visualized by TEE: the antrum was completely visualized in 80 of them (64.5%), partially in 36 (29.0%), and only disappearance of proximal flow could be observed in the remaining 7 PVs (5.7%). Vein occlusion could be achieved in 111 of the 123 (90.2%) visualized PVs. Postinterventional mapping demonstrated electrical isolation in 109 of 111 occluded PVs (positive predictive value 98.2%) and only in 1 of 12 nonoccluded PVs (negative predictive value 91.7%, P < 0.001). After a mean follow-up of 7.4 +/- 3.7 months, 73.3% of patients remained in sinus rhythm without antiarrhythmic drugs. CONCLUSION: Color Doppler documented PV occlusion during cryoballoon ablation can predict effective electrical isolation.