Not to Rush-Laboratory Parameters and Procedural Complications in Patients Undergoing Left Atrial Appendage Closure.

Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3−5) and the median HAS-BLED score was 3 (2−4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65−0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5−68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.

Indications and Outcome in Patients Undergoing Left Atrial Appendage Closure-The Austrian LAAC Registry.

BACKGROUND: Complete real-world data on the indications and outcomes of left atrial appendage closure (LAAC) outside of clinical trials are rare. In this study, we stratified patients undergoing LAAC by indication groups. METHODS: This analysis of the national multicentre Austrian LAAC Registry comprised all patients that underwent LAAC up until 2018 at the currently active centres in Austria. The baseline characteristics, procedural details and outcomes between the following indication groups were compared: bleeding as an indication for LAAC ("bleeding" group) vs. thromboembolism despite oral anticoagulation (OAC; "thromboembolism" group) vs. an intolerance to OAC for reasons other than the above ("other" group). RESULTS: The analysis included 186 patients, with 59.7% in the "bleeding" group, 8.1% in the "thromboembolism" group and 32.2% in the "other" group. The CHADS2 score was the highest in the "thromboembolism" group and the HAS-BLED score was the highest in the "bleeding" group. The procedural outcomes were similar between groups (implantation success, 97.3%), with major complications occurring in 7.0% of patients. One-year survival free from stroke, bleeding or LAAC-associated hospitalisation was 83.9%, 90.0% and 81.4% in the "bleeding", "thromboembolism" and "other" groups, respectively (p = 0.891). CONCLUSIONS: In routine clinical practice, LAAC was used in a heterogeneous patient population with atrial fibrillation (AF) and contraindication, inefficacy or intolerance to OAC. The long-term outcome was favourable in all groups.

Pulsatile hemodynamics in patients with exertional dyspnea: potentially of value in the diagnostic evaluation of suspected heart failure with preserved ejection fraction.

OBJECTIVES: This study sought to test whether measures of pulsatile arterial function are useful for diagnosing heart failure with preserved ejection fraction (HFPEF), in comparison with and in addition to tissue Doppler echocardiography (TDE). BACKGROUND: Increased arterial stiffness and wave reflections are present in most patients with HFPEF. METHODS: Patients with dyspnea as a major symptom were categorized as having HFPEF or no HFPEF, based on invasively derived filling pressures and natriuretic peptide levels. Pulse wave velocity (PWV) was measured invasively (aortic PWV). Aortic pulse pressure (aoPP) and its components (incident pressure wave height, forward wave amplitude; augmented pressure; backward wave amplitude [Pb]) were quantified noninvasively. RESULTS: Seventy-one patients were classified as HFPEF and 65 as no HFPEF (223 patients had intermediate results). Patients with HFPEF were older, more often had hypertension and diabetes, and had larger left atria and higher left ventricular mass. Brachial pulse pressure (bPP), aoPP, and all measures of arterial stiffness and wave reflections were higher in HFPEF patients. Receiver-operating curve analysis-derived area under the curve (AUC) values for separating HFPEF from no HFPEF were 0.823 for E/E' at the medial annulus, the best TDE parameter; 0.816 for bPP; and 0.867, 0.851, and 0.825 for aortic PWV, aoPP, and Pb, respectively. Adding measures of pulsatile function to TDE resulted in an increase in AUC to 0.875 (bPP; p = 0.03) and 0.901 (aoPP; p = 0.005). In comparison with a TDE-based algorithm, net reclassification improvement was 32.9% (p < 0.0001). CONCLUSIONS: Measures of pulsatile arterial hemodynamics may complement TDE for the diagnosis of HFPEF. (Pulsatile and Steady State Hemodynamics in Diastolic Heart Failure; NCT00720525).

Wave reflections, assessed with a novel method for pulse wave separation, are associated with end-organ damage and clinical outcomes.

We recently developed a novel method for assessment of arterial wave reflections (ARCSolver method): based on adopted Windkessel methods, flow curves are estimated from pressure waveforms, and wave separation analysis is performed, yielding the amplitudes of the forward and backward waves. The aim of this study was to investigate their clinical correlates and prognostic impact. In 725 patients (417 men; mean age, 64 years) undergoing coronary angiography, we determined wave reflections from radial tonometry and transfer function-derived aortic waveforms using pulse wave analysis, as well as wave separation analysis. Measures of pulsatile arterial function were statistically significant, although moderately associated with markers of cardiac load and subclinic cardiac, renal, and aortic end-organ damage. After a median follow-up duration of 1399 days, 139 patients reached the combined cardiovascular end point (death, myocardial infarction, stroke, coronary, cerebrovascular, and peripheral revascularization). In univariate analysis, the relative risk of the combined end point increased with increasing levels of incident pressure wave height, augmented pressure, and forward and backward wave amplitude (hazard ratio for 1 SD was 1.302, 1.236, 1.226, and 1.276; P<0.01 for all, respectively). In multivariate analysis, backward wave amplitude was the most consistent predictor of the combined end point. Of note, its predictive value was independent of brachial systolic, diastolic, and mean blood pressures and was superior to brachial pulse pressure. In conclusion, the amplitude of the reflected wave, as assessed with a novel method for wave separation, is associated with hypertensive end organ damage and is an independent predictor of cardiovascular events in high-risk patients.

Validation of a brachial cuff-based method for estimating central systolic blood pressure.

The prognostic value of central systolic blood pressure has been established recently. At present, its noninvasive assessment is limited by the need of dedicated equipment and trained operators. Moreover, ambulatory and home blood pressure monitoring of central pressures are not feasible. An algorithm enabling conventional automated oscillometric blood pressure monitors to assess central systolic pressure could be of value. We compared central systolic pressure, calculated with a transfer-function like method (ARCSolver algorithm), using waveforms recorded with a regular oscillometric cuff suitable for ambulatory measurements, with simultaneous high-fidelity invasive recordings, and with noninvasive estimations using a validated device, operating with radial tonometry and a generalized transfer function. Both studies revealed a good agreement between the oscillometric cuff-based central systolic pressure and the comparator. In the invasive study, composed of 30 patients, mean difference between oscillometric cuff/ARCSolver-based and invasive central systolic pressures was 3.0 mm Hg (SD: 6.0 mm Hg) with invasive calibration of brachial waveforms and -3.0 mm Hg (SD: 9.5 mm Hg) with noninvasive calibration of brachial waveforms. Results were similar when the reference method (radial tonometry/transfer function) was compared with invasive measurements. In the noninvasive study, composed of 111 patients, mean difference between oscillometric cuff/ARCSolver-derived and radial tonometry/transfer function-derived central systolic pressures was -0.5 mm Hg (SD: 4.7 mm Hg). In conclusion, a novel transfer function-like algorithm, using brachial cuff-based waveform recordings, is suited to provide a realistic estimation of central systolic pressure.

Pulse waveform characteristics predict cardiovascular events and mortality in patients undergoing coronary angiography.

OBJECTIVES: Pulse waveform characteristics (Augmentation Index--AIx and pulse wave transit time) are measures of the timing and extent of arterial wave reflections. Although previous studies reported an independent association with cardiovascular morbidity, it remains to be established that waveform characteristics, derived from noninvasive pulse waveform analysis, predict cardiovascular outcomes independent of and additional to brachial blood pressure. METHODS: We prospectively assessed AIx, heart-rate corrected AIx, and pulse wave transit time, using radial applanation tonometry and a validated transfer function to generate the aortic pressure curve, in 520 male patients undergoing coronary angiography. Primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, cardiac, cerebrovascular, and peripheral revascularization. RESULTS: During a follow-up of 49 months, 170 patients reached the primary endpoint. On the basis of Cox proportional hazards regression models, all pressure waveform characteristics predicted the primary endpoint. A 10% increase of AIx and heart-rate corrected AIx was associated with a 20.5% (95% confidence interval 6.5-36.4, P = 0.003) and 31.4% (95% confidence interval 13.2-52.6, P = 0.0004) increased risk of the primary endpoint, respectively. A 10-ms increase of pulse wave transit time was associated with a 20.8% (95% confidence interval 10.8-29.6, P = 0.0001) lower risk of the primary endpoint. In multiple adjusted models, AIx, heart-rate corrected AIx, and pulse wave transit time were independently associated with the combined endpoint even after adjustments for brachial blood pressure, age, extent of coronary artery disease, clinical characteristics, and medications. CONCLUSION: The study provides evidence that pulse waveform characteristics consistently and independently predict cardiovascular events in coronary patients.

Noninvasive determination of carotid-femoral pulse wave velocity depends critically on assessment of travel distance: a comparison with invasive measurement.

OBJECTIVES: European Society of Hypertension guidelines recommend use of carotid- femoral pulse wave velocity (cfPWV) as a favored measure of aortic stiffness. However, there is no consensus on the measurement of distance travelled by the pulse wave along the aorta to the femoral artery. The aim of our study was to compare cfPWV, calculated with commonly used noninvasive methods for travel distance assessment, against aortic PWV measured invasively. METHODS: One hundred and thirty-five patients had aortic PWV measured invasively during cardiac catheterization, from the delay in wave foot and distance travelled as the catheter was withdrawn from the ascending aorta to the aortic bifurcation. On the following day, noninvasive cfPWV was assessed, using the SphygmoCor system, relating the delay between carotid and femoral wavefoot to travel distance, estimated with five different methods on body surface. RESULTS: Mean travel times were in good agreement [(travel time) TTinvasive was 63 ms, TTnoninvasive was 59.3 ms, Spearman's R: 0.8, P < 0.00001]. Mean PWVinvasive was 8.5 m/s. CfPWV, as assessed noninvasively, depended largely on the method used for travel distance estimation: 11.5, 9.9, 8.7, 11.9, and 9.6 m/s, using direct carotid-femoral distance, carotid-femoral minus carotid-suprasternal notch distances, suprasternal notch-femoral minus carotid-suprasternal notch distances, suprasternal notch-femoral plus carotid-suprasternal notch distances, and suprasternal notch-symphysis distance, respectively. There was acceptable correspondence between PWVinvasive and cfPWVnoninvasive (Spearman's R: 0.73-0.77, P < 0.0001). CONCLUSION: For noninvasive assessment of cfPWV, estimation of pulse wave travel distance is critical. Best agreement with invasive measurements was found for the method of subtracting carotid-suprasternal notch distance from suprasternal notch-femoral distance.

Arterial wave reflections and determinants of endothelial function a hypothesis based on peripheral mode of action.

BACKGROUND: Pulse waveform analysis (PWA) for determination of augmentation index (AIx), a measure of arterial wave reflections, has been used to assess endothelial function, but only in combination with provocative pharmacologic testing. We hypothesized that AIx under basal conditions would be related to endothelial function as well. METHODS: We quantified arterial wave reflections as aortic AIx, using applanation tonometry of the radial artery, and PWA in 424 patients (mean age 64.6 years) undergoing coronary angiography. Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase, were determined with a validated ELISA assay. In a group of the patients (n = 160), pulse wave velocity (PWV) was measured invasively during catheter pullback. Statistics were Spearman's correlation coefficient and multiple linear regression models. RESULTS: We observed a positive, statistically significant correlation between AIx and ADMA (R = 0.11, P = .03), that was closer in 134 patients up to 60 years of age (R = 0.28, P = .001). In the latter group, the correlation was independent of age, gender, smoking, lipids, heart rate, diastolic blood pressure (BP), the presence of hypertension or diabetes, and the extent of coronary artery disease. In contrast, we observed a significant (R = 0.19, P = .02) correlation between PWV and ADMA that disappeared after correction for age and BP. CONCLUSIONS: Our cross-sectional data indicate that ADMA levels are associated with increased arterial wave reflections, most likely due to decreased NO activity in small arteries and arterioles. This relationship is more pronounced in patients up to 60 years of age.

Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions.

AIMS: Increased arterial wave reflections are associated with the presence and extent of coronary atherosclerosis and with cardiovascular mortality in selected populations. We prospectively evaluated their prognostic value in the short- and long-term following percutaneous coronary interventions (PCIs). METHODS AND RESULTS: We non-invasively quantified wave reflections [expressed as augmentation index corrected for heart rate of 75 b.p.m. (AIx@75)] using applanation tonometry of the radial artery and a validated transfer function to obtain the corresponding aortic values in 262 patients undergoing PCI. During 2-year follow-up, 61 patients reached the primary endpoint [death, myocardial infarction (MI), and restenosis]. Increasing tertiles of Alx@75 were related to the rate of patients reaching the primary endpoint [15.2, 20 and 35.3%, respectively (P = 0.001)], as well as the secondary endpoints total mortality, myocardial infarction and death plus myocardial infarction (RR for the third vs. the first tertile 4.33, 3.25 and 3.46, respectively, P < 0.05). In a multivariable Cox-regression model, AIx@75 added prognostic value above and beyond clinical risk factors, angiographic variables, and medications (RR 1.8, 95%CI 1.18-2.76 per increasing AIx@75-tertile, P < 0.01). CONCLUSION: Increased arterial wave reflections are independently associated with an increased risk for severe short- and long-term cardiovascular events in patients undergoing PCI.

Lack of association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis.

BACKGROUND: Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent. This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography. METHODS: We studied a total of 100 men and women (41 women, 59 men, age 63.7 +/- 11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics. The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD). RESULTS: From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39). The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04). CONCLUSION: These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.