Sex Differences in Outcomes After Transcatheter Aortic Valve Replacement: A POPular TAVI Subanalysis.

BACKGROUND: Stroke and bleeding are complications after transcatheter aortic valve replacement (TAVR). A higher incidence of bleeding and stroke has been reported in women, but the role of antithrombotic management pre- and post-TAVR has not been studied. OBJECTIVES: The study sought to compare bleeding and ischemic complications after TAVR between women and men stratified by antiplatelet and oral anticoagulant (OAC) regimen. METHODS: The POPular TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation) trial was a randomized clinical trial to test the hypothesis that monotherapy with aspirin or OAC after TAVR is safer than the addition of clopidogrel. The primary endpoints of interest of this post hoc subanalysis were: 1) all bleeding; and 2) a composite of ischemic events consisting of stroke and myocardial infarction. Secondary endpoints were: 1) nonprocedural bleeding; 2) major or life-threatening bleeding; 3) minor bleeding; 4) stroke; 5) myocardial infarction; and 6) all-cause death. RESULTS: A total of 978 patients (466 [47.6%] women) were included in this study. All bleeding and the composite of myocardial infarction and stroke rates were similar between sexes (all bleeding: 106 [22.8%] women vs 121 [23.6%] men; P = 0.815; ischemic events: 26 [5.6%] vs 36 [7.0%]; P = 0.429). However, major or life-threatening bleeding occurred more often in women (58 [12.5%]) vs men (38 [7.4%]) (P = 0.011), most of which were access site bleedings. The use of aspirin pre- and post-TAVR increased major or life-threatening bleeding in women but not in men. CONCLUSIONS: After TAVR, overall bleeding and ischemic outcomes were similar between women and men. However, women had more major or life-threatening bleedings, especially those receiving aspirin pre- and post-TAVR.

Was it worth it? Benefits of transcatheter aortic valve implantation from a patient's perspective.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an important treatment option for patients with severe aortic stenosis. To improve patient selection, shared decision-making is recommended to elicit patients' treatment expectations and goals. We assessed patients' expectations and goals before TAVI treatment and whether these were met after treatment. Additionally, we evaluated how meeting these goals aligned with quality of life and functional recovery. DESIGN: A mixed method study. SETTING: An academic medical center. PARTICIPANTS: Seventy-four patients undergoing TAVI between 2015 and 2017. MEASUREMENTS: Patients' expectations and goals were assessed qualitatively before treatment. Six to twelve months post procedure, quality of life was measured with the EuroQuol-5D and any change in the number of dependencies in (instrumental) activities of daily living was assessed. RESULTS: Mean age of patients was 81.5 years, and 37.8% were male. Regaining the ability to engage in a specific hobby or activity was the most important treatment goal (33 patients, 54.1%), followed by reducing symptoms (19 patients 31.1%). 66.2% of patients stated that their treatment goal was met. Quality of life was higher in this group, as compared with patients who had not met their treatment goal. Twenty-three patients (31.1%) showed functional improvement. CONCLUSION: TAVI patients were quite capable of eliciting treatment goals and a majority stated, after treatment, that these had been met patients' experience of treatment benefits regarding these goals had poor alignment with functional outcomes. This raises questions regarding relevant outcome measurements in this population, and could aid in improving shared decision-making and patient selection for TAVI.

Delirium, functional decline and quality of life after transcatheter aortic valve implantation: An explorative study.

AIM: Transcatheter aortic valve implantation (TAVI) has become an important treatment option for older patients with severe aortic stenosis. However, not all patients benefit from this procedure in terms of functional outcome and quality of life. This complicates patient selection and shared decision-making. Postoperative delirium might negatively affect patient outcomes after TAVI. We therefore studied the potential relationship between postoperative delirium and functional outcome, and how this impacts quality of life after TAVI. METHODS: This was a prospective cohort study of 91 consecutive patients undergoing TAVI between 2015 and 2017 at an academic medical center. All patients underwent a Comprehensive Geriatric Assessment before TAVI. Delirium symptoms were assessed daily during hospitalization. Follow up was carried out between 6 and 12 months postprocedure. The primary outcome was functional decline or death at follow up. Secondarily, we measured quality of life at follow up. RESULTS: The incidence of postoperative delirium was 15.4%. In total, 38.5% of patients experienced functional decline, and 11.0% died during a median follow-up period of 7 months. Delirium resulted in a fourfold increased odds of the combined outcome of functional decline or death. Quality of life was lower in patients that experienced this outcome. CONCLUSION: In a cohort of TAVI patients, functional decline or death was a frequent outcome in the first year postprocedure. Postoperative delirium increased the odds for this outcome substantially. This suggests that delirium risk should be an important factor to consider in shared decision-making for TAVI patients. Geriatr Gerontol Int 2020; 20: 1202-1207.

Sex-Based Differences in Unrecognized Myocardial Infarction.

Background Myocardial infarction is an important cause of morbidity and mortality in both men and women. Atypical or the absence of symptoms, more prevalent among women, may contribute to unrecognized myocardial infarctions and missed opportunities for preventive therapies. The aim of this research is to investigate sex-based differences of undiagnosed myocardial infarction in the general population. Methods and Results In the Lifelines Cohort Study, all individuals ≥18 years with a normal baseline ECG were followed from baseline visit till first follow-up visit (≈5 years, n=97 203). Individuals with infarct-related changes between baseline and follow-up ECGs were identified. The age- and sex-specific incidence rates were calculated and sex-specific cardiac symptoms and predictors of unrecognized myocardial infarction were determined. Follow-up ECG was available after a median of 3.8 (25th and 75th percentile: 3.0-4.6) years. During follow-up, 198 women experienced myocardial infarction (incidence rate 1.92 per 1000 persons-years) compared with 365 men (incidence rate 3.30; P<0.001 versus women). In 59 (30%) women, myocardial infarction was unrecognized compared with 60 (16%) men (P<0.001 versus women). Individuals with unrecognized myocardial infarction less often reported specific cardiac symptoms compared with individuals with recognized myocardial infarction. Predictors of unrecognized myocardial infarction were mainly hypertension, smoking, and higher blood glucose level. Conclusions A substantial proportion of myocardial infarctions are unrecognized, especially in women. Opportunities for secondary preventive therapies remain underutilized if myocardial infarction is unrecognized.

Early Clinical Impact of Cerebral Embolic Protection in Patients Undergoing Transcatheter Aortic Valve Replacement.

Background We aimed to compare the rate of neurological events in patients with or without cerebral embolic protection (CEP) during transcatheter aortic valve replacement (TAVR). Methods and Results Data on clinical end points including neurological events ≤30 days post-TAVR were collected for all patients who underwent transfemoral TAVR in 2 academic tertiary care institutions. Patients were matched through propensity scoring, which resulted in 333 pairs of patients with versus without CEP out of a total of 831 consecutive patients. The median age was 81 (76-85) years, and the median logistic EuroScore was 14% (9%-20%). The CEP group experienced less neurological events at 24 hours (1% versus 4%; P=0.035) and at 30 days (3% versus 7%; P=0.029). There were significantly more disabling strokes in unprotected patients at 30 days (1% versus 4%; P=0.039). CEP was associated with significantly fewer neurological events at 24 hours after TAVR (odds ratio, 0.20; 95% CI, 0.06-0.73; P=0.015) by multiple regression analysis, while age and valve type did not contribute significantly. Overall, 67% (2 of 3) in the CEP versus 83% (10 of 12) in the non-CEP cohort experienced neurological events in protected areas (ie, not dependent on the left vertebral artery). Conclusions The use of filter-based CEP during TAVR was associated with less neurological events, especially in CEP-protected brain territories.

Plasma interleukin 6 levels are associated with cardiac function after ST-elevation myocardial infarction.

BACKGROUND AND AIMS: Myocardial infarction triggers an inflammatory response involved in cardiac repair. We studied the association of the interleukin 6 (IL-6) cascade with infarct size and cardiac function after ST-elevation myocardial infarction (STEMI). METHODS: In 369 STEMI patients IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein (sgp) 130 were measured at baseline (hospital admission), 24 h, 2 weeks, 7 weeks, 4 months, and 1 year post-PCI and sIL-6R/IL-6 ratio was calculated. At 4 months, infarct size and left ventricular ejection fraction (LVEF) were assessed by magnetic resonance imaging. Diastolic function (E/e') was determined by echocardiography. RESULTS: Hospital admission levels for IL-6, sIL-6R, sgp 130 were 3.7 pg/ml (IQR 2.1-6.7 pg/ml), 51.6 ng/ml (IQR 37.3-69.0 ng/ml), and 332 ng/ml (IQR 280-399 ng/ml), respectively. 24 h after admission, IL-6 had increased threefold compared to baseline (p < 0.001) and returned below baseline (p < 0.001) 2 weeks after STEMI. sIL-6R and sgp130 levels at 24 h remained similar to baseline but were increased at 2 weeks (p < 0.001; p < 0.001, respectively). IL-6 and sIL-6R/IL-6 ratio at 24 h were independently associated with infarct size [ß 5.4 (95% CI 3.3-7.5); p < 0.001, ß - 4.0 (95% CI - 6.1 to - 1.9); p < 0.001, respectively]. Higher levels of IL-6 at 24 h were associated with lower LVEF [ß - 4.2 (95% CI -6.7 to - 1.8); p = 0.001]. CONCLUSIONS: Higher IL-6 and lower sIL-6R/IL-6 ratio early after presentation with STEMI are indicative for larger infarct size and decreased cardiac function at 4 months.

Prevalence of electrocardiographic unrecognized myocardial infarction and its association with mortality.

BACKGROUND: Identifying unrecognized myocardial infarction (MI) is important for secondary prevention. The aim of this study is to determine the prevalence and correlates of unrecognized MI and the association with mortality in the general population. METHODS: All participants ≥18years participating in the Lifelines population, a three-generation Cohort Study and Biobank, were included (n=152,180). Participants with unrecognized MI were matched with controls without MI (1:2) based on age and gender. Unrecognized MI was defined when no history of MI was reported in combination with electrocardiographic (ECG) signs corresponding to MI. A history of MI was defined as a reported history of MI in combination with ECG signs and/or the use of antithrombotic medication. RESULTS: MI was present in 1881(1.2%) of participants and was unrecognized in 431 (22.9%) participants. Under the age of 50years, percentages of unrecognized MI relative to the total amount of MI were 34% and 55% in men and women respectively. Compared to recognized MI, classical cardiovascular risk factors were less prevalent in participants with unrecognized MI. During a median follow- up time of 5, 4 and 4years, 4.4%, 6.4% and 2.2% of participants with unrecognized MI, recognized MI and without MI died, respectively. In a multivariable logistic regression unrecognized MI was an independent predictor of death. CONCLUSIONS: The prevalence of unrecognized MI is substantial and classical cardiovascular risk factors are less prevalent in participants with unrecognized MI. Nevertheless, unrecognized MI is associated with mortality. Risk stratification and early diagnosis is necessary to reduce the morbidity and mortality after MI.

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Left ventricular ejection fraction and mortality in patients with ST-elevation myocardial infarction and bundle branch block.

BACKGROUND: The aim of our study is to assess the effect of bundle branch block (BBB) on mortality and left ventricular ejection fraction (LVEF) in ST-elevation myocardial infarction (STEMI) patients treated in the current era of percutaneous reperfusion therapy. PATIENTS AND METHODS: In this retrospective cohort study, a total of 1123 STEMI patients treated in the University Medical Center Groningen from January 2011 until May 2013 were included. The follow-up duration was 2-4 years. Transthoracic echocardiography was performed within 2 weeks after STEMI. RESULTS: In total, 23 (2.0%) patients presented with left BBB and 49 (4.4%) patients presented with right BBB. Two-year mortality after STEMI was 25.0% (n=18) in patients with BBB and 9.2% (n=97, P<0.001) in patients without BBB. Patients with BBB had more frequently a severely reduced LVEF (<30%) [20.0% (n=6) compared with 4.2% (n=21), P=0.002] and less frequently a normal LVEF [16.7% (n=5) compared with 35.7% (n=179), P=0.046]. After multivariable analysis, BBB did not remain an independent predictor of mortality, but was an independent predictor of reduced LVEF. CONCLUSION: The presence of a BBB was an independent predictor of a reduced LVEF. However, we found no effect of BBB on 2-year mortality in the current era of percutaneous reperfusion therapy.

Emergency transcatheter aortic valve implantation in patients with severe aortic regurgitation and a left ventricle assist device: A case report and systematic review.

BACKGROUND: Cardiogenic shock due to severe aortic regurgitation in patients with left ventricle assist devices is a life threatening condition. Here, we consider transcatheter aortic valve implantation as a treatment option. METHODS AND RESULTS: A patient with a left ventricle assist device was presented to us with cardiogenic shock due to severe aortic regurgitation. We successfully implanted a transcatheter aortic valve in emergency setting. The patient recovered and underwent cardiac transplantation three months afterwards. We performed a systematic literature review and identified 10 cases of patients with a left ventricle assist device undergoing transcatheter aortic valve implantation. In these cases, there was no procedural related mortality reported. In four (40%) patients, transcatheter aortic valve implantation resulted in significant paravalvular aortic regurgitation. In two of these cases it was due to migration of the valve towards the left ventricle. CONCLUSIONS: Our case report and review of literature suggests that transcatheter aortic valve implantation is a feasible and lifesaving treatment option for left ventricle assist device patients presenting with severe aortic regurgitation.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.