Left atrial pump strain predicts long-term survival after transcatheter aortic valve implantation.

BACKGROUND: This study aims at investigating left atrial (LA) deformation by left atrial reservoir (LARS) and pump strain (LAPS) and its implications for long-term survival in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: Speckle tracking echocardiography was performed in 198 patients with severe AS undergoing TAVI. Association of strain parameters with cardiovascular mortality was determined. RESULTS: Over a follow-up time of 5 years, 49 patients (24.7%) died. LAPS was more impaired in non-survivors than survivors (P = 0.010), whereas no difference was found for LARS (P = 0.114), LA ejection fraction (P = 0.241), and LA volume index (P = 0.292). Kaplan-Meier analyses yielded a reduced survival probability according to the optimal threshold for LAPS (P = 0.002). A more impaired LAPS was associated with increased mortality risk (HR 1.12 [95% CI 1.02-1.22]; P = 0.014) independent of LVEF, LAVI, age, and sex. Addition of LAPS improved multivariable echocardiographic (LVEF, LAVI) and clinical (age, sex) models with potential incremental value for mortality prediction (P = 0.013 and P = 0.031, respectively). In contrast, LARS and LAVI were not associated with mortality. CONCLUSIONS: In patients undergoing aortic valve replacement for severe AS, LAPS was impaired in patients dying during long-term follow-up after TAVI, differentiated survivors from non-survivors, was independently associated with long-term mortality, and yielded potential incremental value for survival prediction after TAVI. LAPS seems useful for risk stratification in severe AS and timely valve replacement.

Mitral annular disjunction in patients with severe aortic stenosis: Extent and reproducibility of measurements with computed tomography.

OBJECTIVES: To determine with CT the prevalence and extent of mitral annular disjunction (MAD) in patients undergoing transcatheter aortic valve replacement (TAVR) and its association with mitral valve disease and arrhythmia. METHODS: We retrospectively evaluated 408 patients (median age, 82 years; 186 females) with severe aortic stenosis undergoing ECG-gated cardiac CT with end-systolic data acquisition. Baseline and follow-up data were collected in the context of a national registry. Two blinded, independent observers evaluated the presence of MAD on multi-planar reformations. Maximum MAD distance (left atrial wall-mitral leaflet junction to left ventricular myocardium) and circumferential extent of MAD were assessed on CT using dedicated post-processing software. Associated mitral valve disease was determined with echocardiography. RESULTS: 7.8 % (32/408) of patients with severe aortic stenosis had MAD. The maximum MAD was 3.5 mm (interquartile range: 3.0-4.0 mm). The circumferential extent of MAD comprised 34 ±â€¯15 % of the posterior and 26 ±â€¯12 % of the entire mitral annulus. Intra- and interobserver agreement for the detection of MAD on CT were excellent (kappa: 0.90 ±â€¯0.02 and 0.92 ±â€¯0.02). Mitral regurgitation (p = 1.00) and severe mitral annular calcification (p = 0.29) were similarly prevalent in MAD and non-MAD patients. Significantly more patients with MAD (6/32; 19 %) had mitral valve prolapse compared to those without (6/376; 2 %; p < 0.001). MAD was not associated with arrhythmia before and after TAVR (p > 0.05). CONCLUSIONS: Using CT, MAD was found in 7.8 % of patients with severe aortic stenosis, with a higher prevalence in patients with mitral valve prolapse. We found no association of MAD with arrhythmia before or after TAVR.

Mitral annular calcification in the elderly - Quantitative assessment.

PURPOSE: To determine the reliability of subjective and objective quantification of mitral annular calcification (MAC) in elderly patients with severe aortic stenosis, to define quantitative sex- and age-related reference values of MAC, and to correlate quantitative MAC with mitral valve disease. METHODS: In this retrospective, IRB-approved study, we included 559 patients (268 females, median age 81 years, inter-quartile range 77-85 years) with severe aortic stenosis undergoing CT. Four independent readers performed subjective MAC categorization as follows: no, mild, moderate, and severe MAC. Two independent readers performed quantitative evaluation of MAC using the Agatston score method (AgatstonMAC). Mitral valve disease was determined by echocardiography. RESULTS: Subjective MAC categorization showed high inter-reader agreement for no (k â€‹= â€‹0.88) and severe MAC (k â€‹= â€‹0.75), whereas agreement for moderate (k â€‹= â€‹0.59) and mild (k â€‹= â€‹0.45) MAC was moderate. Intra-reader agreement for subjective MAC categorization was substantial (k â€‹= â€‹0.69 and 0.62). Inter- and intra-reader agreement for AgatstonMAC were excellent (ICC â€‹= â€‹0.998 and 0.999, respectively), with minor inconsistencies in MAC involving the left ventricular outflow tract/aortic valve. There were significantly more women than men with MAC (n â€‹= â€‹227, 85% versus n â€‹= â€‹209, 72%; p â€‹< â€‹0.001), with a significantly higher AgatstonMAC (median 597, range 81-2055 versus median 244; range 0-1565; p â€‹< â€‹0.001), particularly in patients ≥85 years of age. AgatstonMAC showed an area-under-the-curve of 0.84 to diagnose mitral stenosis, whereas there was no association of AgatstonMAC with mitral regurgitation (p â€‹> â€‹0.05). CONCLUSIONS: Our study in elderly patients with severe aortic stenosis shows that quantitative MAC scoring is more reliable than subjective MAC assessment. Women show higher AgatstonMAC scores than men, particularly in the elderly population. AgatstonMAC shows high accuracy to diagnose mitral stenosis.

Bending the Rules in Transfemoral TAVI With the SAPIEN 3: Overcoming Severe Iliac Tortuosity.

Whilst the worldwide uptake of transcatheter aortic valve implantation (TAVI) over the last 10 years has been dramatic, iliac tortuosity remains a potential barrier to the most commonly chosen access route via the femoral artery. We describe the challenges posed by severe iliac tortuosity during transfemoral TAVI and contrast a difficult procedure - at the limit of the capability of current device delivery technology - with a straightforward implantation. The use of pre-procedural multi-detector computed tomography to assess the vasculature and a bilateral stiff wire technique for managing iliofemoral tortuosity are discussed.

MSCT guided sizing of the Edwards Sapien XT TAVI device: impact of different degrees of oversizing on clinical outcome.

AIMS: Prospective data on the usage of 3-dimensional imaging based annulus sizing on the outcome of TAVI is not available yet and there is general uncertainty about the optimal degree of oversizing. In the current study we therefore assessed a 3-D MSCT guided over-sizing approach and evaluated the clinical outcome of different degrees of oversizing. METHODS: TAVI-size-selection was done using systolic MSCT-annulus cross-sectional-area (CSA) measurements in 107 patients with severe aortic stenosis with the goal to oversize the 3rd generation balloon expandable Edwards Sapien XT (ESTV) device in relation to the native aortic annulus CSA. RESULTS: Among different degrees of oversizing there were no differences in the occurrence of stroke, myocardial infarction and death. No aortic injuries were observed. The overall rate of >mild postprocedural aortic regurgitation (PAR) was 7.6%. Increasing oversizing ratios are associated with lower rates of >mild PAR (r = -0.236, p<0.02) with the lowest rate of >mild PAR in patients with area based oversizing ratios >25% and the highest rate in patients with oversizing ratios <15% (0% vs. 15.8%, p<0.02). The rate of postprocedural permanent pacemakers tended to be lower in patients with <15% oversizing compared to those with >25% oversizing (5.3 vs. 16.7%, p<0.23). CONCLUSIONS: MSCT guided ESTV-device sizing is safe and is associated with significantly lower than previously reported rates for PAR. A device/annulus oversizing ratio of 15-25% based on area and 7-12% based on mean diameter appears to provide the best risk-benefit ratio in terms of PAR reduction and conduction disorders.

Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin.

BACKGROUND: Lipid-lowering therapy can improve endothelial function in patients with coronary artery disease (CAD) and hypercholesterolemia. Little is known about induced changes in myocardial microcirculation. This study prospectively investigated the temporal effects of lipid-lowering therapy with fluvastatin on coronary flow and flow reserve (CFR) in patients with CAD assessed by PET. METHODS AND RESULTS: In an open clinical trial, CFR was studied in 15 patients with angiographically documented multivessel CAD and hypercholesterolemia (LDL >160 mg/dL). Dynamic 13N-labeled ammonia PET imaging in conjunction with adenosine was used to assess regional and global CFR at baseline as well as at 2 and 6 months during treatment with fluvastatin (60 to 80 mg/d). Despite a rapid decrease in total cholesterol (29+/-6%) and LDL (37+/-9%), myocardial blood flow at rest and during stress was unchanged after 2 months of treatment (2.7+/-0.9 versus 2.5+/-0.6 mL x g-1 x min-1). At 6 months, stress blood flow as well as CFR increased significantly (3.4+/-1.0 mL x g-1 x min-1). No change in hemodynamic parameters was noted during the entire study. Nine of 15 patients increased CFR by >20%. All responders demonstrated improvement in anginal symptoms, whereas nonresponders stated no change (n=4) or worsening of symptoms (n=2). The improvement in CFR was not related to the amount of lipid lowering and was independent of the severity of stenoses. CONCLUSIONS: Improvement in stress blood flow and CFR is delayed compared with the lipid-lowering effect of fluvastatin, suggesting a slow recovery of the vasodilatory response to adenosine.

B2 bradykinin receptors in cultured neonatal rat cardiomyocytes mediate a negative chronotropic and negative inotropic response.

Receptors for bradykinin (BK) were characterized in primary cultures of beating neonatal rat cardiomyocytes using [3H]BK was radioligand. Degradation studies demonstrated that [3H]BK was stable for at least 2 h when incubated with cardiomyocytes at 2 and 37 degrees C in the presence of bacitracin in combination with captopril or ramiprilat. Without these inhibitors, > 80% of the [3H]BK was degraded within 2 h at 37 degrees C. This indicates that angiotensin-converting enzyme (ACE) is responsible for the main BK-degrading activity in cardiomyocytes. Scatchard plots were linear and gave a Kd of 1.5 +/- 0.8 nmol/l (mean +/- SD, n = 4) and a maximum binding capacity of 55-125 fmol/mg protein. Association and dissociation studies showed that binding of [3H]BK was saturable and reversible. Binding of [3H]BK at 37 degrees C led to internalization of the ligand. Competition studies with B1 and B2 agonists and antagonists were consistent with a B2 subtype of receptor. Addition of BK to beating cardiomyocytes (> 1 nmol/l) at 37 degrees C gave a strong but transient negative chronotropic effect. This response was paralleled by changes in the pulsation amplitude, which indicated a simultaneous negative inotropic effect of BK. These results provide a basis for the hypothesis that ACE inhibition exerts its cardioprotective effect at the level of a population of cardiomyocytes by virtue of kinin receptor-mediated mechanisms.