Impact of transcatheter aortic valve implantation on mechanical dispersion

Objectives The physiological determinants of left ventricular (LV) mechanical dispersion (MD) are not fully explored. We aimed to investigate the impact of afterload reduction and changes in ventricular conduction on LV MD after transcatheter aortic valve implantation (TAVI). Methods Patients with severe aortic stenosis (AS) were examined in a prospective, repeated measures observational cohort study before and after an uncomplicated transfemoral TAVI in a single tertiary centre. LV MD was assessed by speckle tracking echocardiography. Valvulo-arterial impedance (ZVA) was used as a measure of global afterload. Results We included 140 consecutive patients (83±8 years old, 49% women, logistic EuroSCORE 16±10) with severe AS (valve area 0.7±0.2 cm 2 , mean transvalvular gradient 54±18 mm Hg) and a relatively preserved LV ejection fraction (52%±11%). After TAVI, we observed favourable changes in transvalvular gradients and ZVA in all patients. Compared with baseline, postprocedural MD was significantly lower in 108 patients with unchanged ventricular conduction (55±17 ms vs 51±17 ms, p=0.02) and higher in 28 patients with TAVI-induced left bundle branch block (51±13 ms vs 62±19 ms, p≤0.001). During 22±9 months observation, 22 patients died. Postprocedural MD was associated with mortality in a univariate Cox regression model (HR=1.24 (1.01–1.52), p<0.04, per 10 ms increase). Conclusions Isolated afterload reduction was associated with reduction of MD, while concomitant impairment of ventricular conduction resulted in a more pronounced MD after TAVI, indicating that loading conditions and conduction should be considered when evaluating MD. A pronounced postprocedural LV MD was associated with mortality

Safety and feasibility of dobutamine stress echocardiography in symptomatic high gradient aortic stenosis patients scheduled for transcatheter aortic valve implantation

Purpose We aimed to study the safety and feasibility of low‐dose dobutamine stress echocardiography in a symptomatic high gradient aortic stenosis population scheduled for transfemoral transcatheter aortic valve implantation (TAVI) and to quantify left ventricular (LV) flow reserve. Methods Fifty patients underwent dobutamine stress echocardiography with 5 minutes increments of 5 μg/kg/min up to 20 μg/kg/min until the heart rate increased ≥20 beats/min from baseline or exceeded 100 beats/min. Other criteria for discontinuing the infusion were major adverse events: ventricular arrhythmia, persistent supraventricular arrhythmia, pulmonary edema, chest pain with significant ST‐changes, or minor events: ST‐changes, drop in systolic blood pressure >30 mmHg, mild chest pain, and/or dyspnea. LV flow reserve was defined as an increase in stroke volume ≥20% during the test. Results Of 50 patients, 45 completed the test according to protocol. No patient had major adverse event. Five patients experienced minor side effects: mild chest pain/dyspnea in three, self‐terminating atrial flutter in one, and decrease in blood pressure in one. Significant LV flow reserve was observed in 20 patients (40%). Conclusion Low‐dose dobutamine stress test appeared safe and feasible patients with high gradient aortic stenosis, and showed LV flow reserve in a minority of them

Classical mechanical dyssynchrony is rare in transcatheter aortic valve implantation-induced left bundle branch block

Aims Left bundle branch block (LBBB) is a frequent conduction abnormality after transcatheter aortic valve implantation (TAVI). We aimed to investigate how TAVI procedure related conduction abnormalities influence ventricular mechanics and prognosis, with particular focus on new-onset persistent LBBB. Methods and results A total of 140 consecutive patients with severe aortic stenosis (83 ± 8 years old, 49% women) undergoing TAVI in a single tertiary centre were included in a repeated measures study. Changes in myocardial function and contraction patterns were investigated in relation to changes in electrical conduction and afterload by speckle tracking echocardiography. Whether patients with new-onset LBBB acquired classical dyssynchronous contractions was assessed by longitudinal strain in apical four-chamber view. Global longitudinal strain improvement was seen in all patients (−15.1 ± 4.3 vs. −16.1 ± 3.9%, P < 0.01, n = 140), and all subgroups, regardless of pre-existing or procedure-acquired conduction abnormalities immediately after TAVI. New-onset LBBB fulfilling strict electrocardiogram (ECG) criteria was observed in 28 patients (20%). The vast majority of new-onset LBBB patients (n = 26, 93%) had homogenous contractions. Classical dyssynchronous LBBB contractions were only observed in 2 patients (7%) with new-onset LBBB. Patients with new-onset LBBB and patients without acquired conduction disorders had similar mortality rates during 19 ± 9 months of follow-up [11.1, 95% confidence interval (CI) 4.6–26.8 vs. 8.1, 95% CI 4.8–13.7 per 100 patients years, P = 0.53]. Conclusion Classical dyssynchronous LBBB contractions were absent in most patients with new-onset post-TAVI LBBB, even when applying strict ECG criteria. Patients with and without new-onset LBBB experienced similar prognosis with regards to mortality

Microvascular function and inflammatory activation in Takotsubo cardiomyopathy

Abstract Aims The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS‐induced pathology. Methods and results The study included 20 females [median age 65 years; interquarile range (IQR) = 58–70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, we determined the index of microvascular resistance (IMR) and drew blood samples almost simultaneously from the aorta and coronary sinus. Cardiac magnetic resonance imaging (MRI) was done in the acute phase. We present descriptive coronary physiology and cardiac MRI data and compare inflammatory biomarkers between samples from the aorta, coronary sinus, and venous samples after 3 months using the Wilcoxon signed‐rank test. For comparison, we also analysed the actual biomarkers in venous blood from 15 healthy female controls. A supplementary analysis explored Spearman's rank correlation between the inflammatory biomarkers, IMR, MRI data, and cardiac biomarkers. The median IMR was 16.5 mmHg·s (IQR = 10.5–28.2 mmHg·s), which was only slightly higher than that in the reference populations. Seven (35%) of the study subjects had IMR > 25 mmHg·s, suggesting a microvascular dysfunction. IMR was not affected by time from symptom onset. According to MRI, the apical region of the left ventricle was affected in 65% of the subjects. The median ejection fraction was 41% (IQR = 31–48%). Biomarker analyses revealed elevation of markers for extracellular matrix remodelling and fibrosis, inflammation, immune activation, and upstream inflammation as compared with healthy controls. Only the levels of interleukin (IL)‐1 receptor antagonist and soluble T‐cell immunoglobulin mucin domain‐3 (sTIM‐3) were higher in the coronary sinus than in the aorta. No variable was significantly correlated with IMR. The IL‐6 level in the aorta was inversely correlated with the left ventricular ejection fraction. Growth differentiation factor‐15, osteoprotegerin, and von Willebrand factor levels in both aorta and coronary sinus were positively correlated with N‐terminal‐pro‐brain‐natriuretic peptide, while the correlations of IL‐6 and sTIM‐3 with N‐terminal‐pro‐brain‐natriuretic peptide were restricted to the aorta and coronary sinus, respectively. While most of the markers were within normal limits after 3 months, matrix metalloproteinase‐9 increased during follow‐up to reach levels higher than those in the healthy controls. Conclusion The median IMR was only slightly elevated in this study, but about one‐third of the patients had values indicating microvascular dysfunction. The present study supports the involvement of several inflammatory pathways in TTS, including monocyte/macrophage activation, with sTIM‐3 as a potential novel marker

Outcomes in asymptomatic, severe aortic stenosis

Background and aim of the study Patients with asymptomatic, severe aortic stenosis are presumed to have a benign prognosis. In this retrospective cohort study, we examined the natural history of contemporary patients advised against aortic valve replacement due to a perceived lack of symptoms. Materials and methods We reviewed the medical records of every patient given the ICD-10-code for aortic stenosis (I35.0) at Oslo University Hospital, Rikshospitalet, between Dec 1st, 2002 and Dec 31st, 2016. Patients who were evaluated by the heart team due to severe aortic stenosis were categorized by treatment strategy. We recorded baseline data, adverse events and survival for the patients characterized as asymptomatic and for 100 age and gender matched patients scheduled for aortic valve replacement. Results Of 2341 patients who were evaluated for aortic valve replacement due to severe aortic stenosis, 114 patients received conservative treatment due to a lack of symptoms. Asymptomatic patients had higher mortality than patients who had aortic valve replacement, log-rank p<0.001 (mean follow-up time: 4.0 (SD: 2.5) years). Survival at 1, 2 and 3 years for the asymptomatic patients was 88%, 75% and 63%, compared with 92%, 83% and 78% in the matched patients scheduled for aortic valve replacement. 28 (25%) of the asymptomatic patients had aortic valve replacement during follow-up. Age, previous history of coronary artery disease and N-terminal pro B-type natriuretic peptide (NT-proBNP) were predictors of mortality and coronary artery disease and NT-proBNP were predictors of 3-year morbidity in asymptomatic patients. Conclusions In this retrospective study, asymptomatic patients with severe aortic stenosis who were advised against surgery had significantly higher mortality than patients who had aortic valve replacement

Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study

Introduction - Many women undergoing coronary angiography for chest pain have no or only minimal coronary artery disease (CAD). However, despite the lack of obstructive CAD, they still have an increased risk of major adverse cardiovascular events. Pleiotropic effects of statins may influence microvascular function, but if statins improve microvascular function in unselected chest pain patients is not well studied. This study assessed microvascular function by using the thermodilution‐derived test “the index of microvascular resistance” (IMR) with the aim of determining the (i) IMR level in women with chest pain and non‐obstructive CAD and if (ii) IMR is modified by high‐dose statin treatment in these patients. Additional objectives were to identify the influence of statins on the health status as assessed with generic health questionnaires and on biomarkers of endothelial activation. Materials and methods - The study was a randomized, double‐blind, single‐center trial comparing 6 months of rosuvastatin treatment with placebo. In total, 66 women without obstructive CAD were included. Mean age was 52.7 years and 55.5 years in the placebo and rosuvastatin group, respectively. Microvascular function was assessed using the IMR, health status was assessed using the SF‐36 and EQ‐5D questionnaires, and biochemical values were assessed at baseline and 6 months later. Results and conclusions - In the placebo group IMR was 14.6 (SD 5.7) at baseline and 14.4 (SD 6.5) at follow‐up. In the rosuvastatin group IMR was 16.5 (SD 7.5) at baseline and 14.2 (SD 5.8) at follow‐up. IMR did not differ significantly between the two study groups at follow‐up controlled for preintervention values. C‐reactive protein (CRP) was comparable between the groups at baseline, while at follow‐up CRP was significantly lower in the rosuvastatin group compared to placebo [0.6 (±0.5) mg/L vs. 2.6 (±3.0) mg/L; p = 0.002]. Whereas rosuvastatin treatment for 6 months attenuated CRP levels, it did not improve microvascular function as assessed by IMR (Clinical Trials.gov NCT 01582165, EUDRACT 2011‐002630‐39.3tcAZ)

Clinical and echocardiographic parameters predicting 1- and 2-year mortality after transcatheter aortic valve implantation

Background: Transcatheter aortic valve implantation (TAVI) has become a standard treatment option for patients with symptomatic aortic stenosis. Elderly high-risk patients treated with TAVI have a high residual mortality due to preexisting comorbidities. Knowledge of factors predicting futility after TAVI is sparse and clinical tools to aid the preoperative evaluation are lacking. The aim of this study was to evaluate if echocardiographic measures, including speckle-tracking analysis, in addition to clinical parameters, could aid in the prediction of mortality beyond 30 days after TAVI. Methods: This prospective observational cohort study included 227 patients treated with TAVI at the University Hospital of North Norway, Tromsø and Oslo University Hospital, Rikshospitalet from February 2010 to June 2013. All the patients underwent preoperative echocardiographic evaluation with retrospective speckle-tracking analysis. Primary endpoints were 1- and 2-year mortality beyond 30 days after TAVI. Results: All-cause 1- and 2-year mortality beyond 30 days after TAVI was 12.1 and 19.5%, respectively. Predictors of 1-year mortality beyond 30 days were body mass index [hazard ratio (HR): 0.88, 95% CI: 0.80–0.98, p = 0.018], previous myocardial infarction (HR: 2.69, 95% CI: 1.14–6.32, p = 0.023), and systolic pulmonary artery pressure ≥ 60 mm Hg (HR: 5.93, 95% CI: 1.67–21.1, p = 0.006). Moderate-to-severe mitral regurgitation (HR: 2.93, 95% CI: 1.53–5.63, p = 0.001), estimated glomerular filtration rate (HR: 0.98, 95% CI: 0.96–0.99, p = 0.002), and chronic obstructive pulmonary disease (HR: 1.9, 95% CI: 1.01–3.58, p = 0.046) were predictors of 2-year mortality. Conclusion: Both the clinical and echocardiographic parameters should be considered when evaluating high-risk patients for TAVI, as both are predictive of 1-and 2-year mortality. Our results support the importance of individual risk assessment using a multidisciplinary, multimodal, and individual approach

Clinical and echocardiographic parameters predicting 1- and 2-year mortality after transcatheter aortic valve implantation

Background: Transcatheter aortic valve implantation (TAVI) has become a standard treatment option for patients with symptomatic aortic stenosis. Elderly high-risk patients treated with TAVI have a high residual mortality due to preexisting comorbidities. Knowledge of factors predicting futility after TAVI is sparse and clinical tools to aid the preoperative evaluation are lacking. The aim of this study was to evaluate if echocardiographic measures, including speckle-tracking analysis, in addition to clinical parameters, could aid in the prediction of mortality beyond 30 days after TAVI. Methods: This prospective observational cohort study included 227 patients treated with TAVI at the University Hospital of North Norway, Tromsø and Oslo University Hospital, Rikshospitalet from February 2010 to June 2013. All the patients underwent preoperative echocardiographic evaluation with retrospective speckle-tracking analysis. Primary endpoints were 1- and 2-year mortality beyond 30 days after TAVI. Results: All-cause 1- and 2-year mortality beyond 30 days after TAVI was 12.1 and 19.5%, respectively. Predictors of 1-year mortality beyond 30 days were body mass index [hazard ratio (HR): 0.88, 95% CI: 0.80–0.98, p = 0.018], previous myocardial infarction (HR: 2.69, 95% CI: 1.14–6.32, p = 0.023), and systolic pulmonary artery pressure ≥ 60 mm Hg (HR: 5.93, 95% CI: 1.67–21.1, p = 0.006). Moderate-to-severe mitral regurgitation (HR: 2.93, 95% CI: 1.53–5.63, p = 0.001), estimated glomerular filtration rate (HR: 0.98, 95% CI: 0.96–0.99, p = 0.002), and chronic obstructive pulmonary disease (HR: 1.9, 95% CI: 1.01–3.58, p = 0.046) were predictors of 2-year mortality. Conclusion: Both the clinical and echocardiographic parameters should be considered when evaluating high-risk patients for TAVI, as both are predictive of 1-and 2-year mortality. Our results support the importance of individual risk assessment using a multidisciplinary, multimodal, and individual approach