Prevalence and severity of cognitive dysfunction in patients referred for transcatheter aortic valve implantation (TAVI): clinical and cognitive impact at 1 year.

AIM: We estimated the proportion and severity of cognitive disorders in an unselected population of patients referred for transcatheter aortic valve implantation (TAVI). Second, we describe clinical and cognitive outcomes at 1 year. METHODS: Eligible patients were aged ≥ 70 years, with symptomatic aortic stenosis and an indication for TAVI. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction (CD), defined as no CD if score ≥ 26, mild CD if 18-25; moderate CD if 10-18, and severe CD if < 10. We assessed survival and in-hospital complications at 6 months and 1 year. RESULTS: Between June 2019 and October 2020, 105 patients were included; 21 (20%) did not undergo TAVI, and thus, 84 were analyzed; median age 85 years, 53.6% females, median EuroScore 11.5%. Median MoCA score was 22 (19-25); CD was excluded in 18 (21%), mild in 50 (59.5%), moderate in 15 (19%) and severe in 1. Mean MoCA score at follow-up was 21.9(± 4.69) and did not differ significantly from baseline (21.79 (± 4.61), p = 0.73). There was no difference in success rate, in-hospital complications, or death across CD categories. CONCLUSION: The clinical course of patients with mild or moderate CD is not different at 1 year after TAVI compared to those without cognitive dysfunction.

Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients with Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting).

BACKGROUND: No randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndromes. METHODS: We conducted a multicenter, randomized study involving 240 patients with non-ST-segment elevation acute coronary syndromes to compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group) to fluoroscopy-guided PCI (angiography-guided group). The primary end point was the functional result of PCI assessed by the measure of post PCI fractional flow reserve. Secondary end points included procedural complications and type 4a periprocedural myocardial infarction. Safety was assessed by the rate of acute kidney injury. RESULTS: OCT use led to a change in procedural strategy in 50% of the patients in the OCT-guided group. The primary end point was improved in the OCT-guided group, with a significantly higher fractional flow reserve value (0.94±0.04 versus 0.92±0.05, P=0.005) compared with the angiography-guided group. There was no significant difference in the rate of type 4a myocardial infarction (33% in the OCT-group versus 40% in the angiography-guided group, P=0.28). The rates of procedural complications (5.8%) and acute kidney injury (1.6%) were identical in each group despite longer procedure time and use of more contrast medium in the OCT-guided group. Post-PCI OCT revealed stent underexpansion in 42% of patients, stent malapposition in 32%, incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led to the more frequent use of poststent overdilation in the OCT-guided group versus the angiography-guided group (43% versus 12.5%, P<0.0001) with lower residual stenosis (7.0±4.3% versus 8.7±6.3%, P=0.01). CONCLUSIONS: In patients with non-ST-segment elevation acute coronary syndromes, OCT-guided PCI is associated with higher postprocedure fractional flow reserve than PCI guided by angiography alone. OCT did not increase periprocedural complications, type 4a myocardial infarction, or acute kidney injury. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01743274.

A phase 2 randomized trial to evaluate the impact of a supervised exercise program on cardiotoxicity at 3 months in patients with HER2 overexpressing breast cancer undergoing adjuvant treatment by trastuzumab: design of the CARDAPAC study.

BACKGROUND: The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is a poor prognosis. Trastuzumab improves overall survival but is associated with cardiotoxicity, especially a decline in left ventricular ejection fraction (LVEF). In addition, chemotherapy and radiotherapy increase fatigue and pain, decrease physical capacity and health-related quality of life. To date, no study has evaluated the benefits of physical activity on the side effects of treatment in patients with HER2 positive breast cancer. The aim of this study is to evaluate the impact of 3 months' exercise intervention on myocardial function and in particular on the rate of cardiotoxicity. METHODS: This multicenter, randomized clinical trial will include 112 patients treated by adjuvant trastuzumab for HER2 positive breast cancer to investigate the effects of a 3 months' supervised exercise program (intermittent exercise, combining moderate and high intensities; 55 minutes duration, 3 times per week), on the rate of cardiotoxicity [defined by either a decrease of the LVEF under 50% or an absolute drop of LVEF of 10%] between baseline and at 3 months and on strength, aerobic capacity, metabolic, inflammatory and hormonal parameters. Health-related quality of life, fatigue, pain and level of physical activity will also be assessed. Participants are randomly allocated to one of the two groups ("training group" vs "standard oncological care"). Performance-based and self-reported outcomes are assessed at baseline, at the end of supervised exercise program and at six months follow-up. DISCUSSION: Although physical exercise is recommended to reduce the side effects of adjuvant treatments in breast cancer patients, no randomized study has been conducted to assess the benefits of a physical training program in patients with HER2 overexpressing breast cancer. Cardiac toxicity of trastuzumab may be minimized with an exercise program combining high and moderate intensities. This type of program may be safe, feasible and effective but also increase cardiorespiratory fitness and improve health-related quality of life. If these benefits are confirmed, this exercise intervention could be systematically proposed to patients during the course of treatment by trastuzumab in addition to standard oncological care. TRIAL REGISTRATION: National Clinical Trials Number ( NCT02433067 ); Registration 28 april 2015.

[Management of coronary artery disease at the acute phase]. / Prise en charge d'une mnaladie coronarienne au stade aigu.

In patients with acute coronary syndrome (ACS), early management is of prime importance. However, the median time taken by the patient to call the emergency services is often very long, up to 2 hours. The presence of a physician as first responder ensures good quality resuscitation in case of cardiac arrest, and allows recording of a first ECG, which can be very informative, especially in ACS without ST segment elevation. Treatment at this stage is limited to sublingual nitroglycerin and aspirin. If the first ECG shows ST segment elevation, the patient should be immediately oriented for reperfusion, usually by percutaneous coronary intervention. in the absence of ST segment elevation, the diagnosis of ACS remains unconfirmed. This does not imply that the risk is lesser, but rather that the risk cannot be evaluated accurately in the pre-hospital setting. The use of risk scores can guide the choice of management towards an invasive strategy, including coronary angiography (immediately, or within 24-72 hours). Low-risk patients are candidates for an invasive strategy, provided non-invasive tests demonstrate the presence of ischemia. During the hospital phase, antiplatelet treatment should be initiated and must be adapted to the patient bleeding and thrombotic risk. Clopidogrel is recommended only in patients who are not amenable to prasugrel or ticagrelor. Statin therapy should be initiated from day one, regardless of the initial cholesterol level, preferably with 80 mg atorvastatin. Angiotensin-converting enzyme inhibitors and beta-blockers should also be prescribed to complete the medical prescription both in-hospital and in the long term.

Cardiotoxicity is mitigated after a supervised exercise program in HER2-positive breast cancer undergoing adjuvant trastuzumab.

Background: Trastuzumab is used, alone or in conjunction with standard chemotherapy, to treat HER2-positive breast cancer (BC). Although it improves cancer outcomes, trastuzumab. can lead to cardiotoxicity. Physical exercise is a safe and effective supportive therapy in the management of side effects, but the cardioprotective effects of exercise are still unclear. Objectives: The primary aim of this study was to test whether trastuzumab-induced cardiotoxicity [left ventricular ejection fraction (LVEF) under 50%, or an absolute drop in LVEF of 10%] was reduced after a supervised exercise program of 3 months in patients with HER2-positive breast cancer. Secondary endpoints were to evaluate (i) cardiotoxicity rates using other criteria, (ii) cardiac parameters, (iii) cardiorespiratory fitness and (iv) whether a change in LVEF influences the cardiorespiratory fitness. Methods: 89 women were randomized to receive adjuvant trastuzumab in combination with a training program (training group: TG; n = 46) or trastuzumab alone (control group: CG; n = 43). The primary and secondary endpoints were evaluated at the end of the supervised exercise program of 3 months (T3). Results: After exercise program, 90.5 % of TG patients and 81.8% of CG patients did not exhibit cardiotoxicity. Furthermore, whatever the used criterion, percentage of patients without cardiotoxicity were greater in TG (97.6 and 100% respectively) than in CG (90.9 and 93.9% respectively). LVEF and GLS values remained stable in both groups without any difference between the groups. In contrast, at T3, peak VO2 (+2.6 mL.min-1.kg-1; 95%CI, 1.8 to 3.4) and maximal power (+21.3 W; 95%CI, 17.3 to 25.3) increased significantly in TG, whereas they were unchanged in CG (peak VO2: +0.2 mL.min-1.kg-1; 95%CI, -0.5 to 0.9 and maximal power: +0.7 W, 95%CI, -3.6 to 5.1) compared to values measured at T0. No correlation between LVEF changes and peak VO2 or maximal power was observed. Conclusion: A 12-week supervised exercise regimen was safe and improved the cardiopulmonary fitness in particular peak VO2, in HER2-positive BC patients treated with adjuvant trastuzumab therapy. The study is under powered to come to any conclusion regarding the effect on cardiotoxicity. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT02433067.

Takotsubo cardiomyopathy triggered by delirium tremens in a cirrhotic patient with acute-on-chronic liver failure: A case report.

A 64-year-old cirrhotic woman was admitted for alcoholic hepatitis associated with renal failure. Subsequently, she displayed symptoms of alcohol withdrawal progressing to delirium tremens. During hospitalization, she developed acute respiratory distress. The electrocardiogram showed diffuse anteroseptal ST elevation. Transthoracic echocardiography revealed systolic left ventricular apical balloon-like dilation, hypokinesis of the left ventricular mid- and apical segments, and a left ventricular ejection fraction of 30%. Coronary angiography was normal and led to the diagnosis of Takotsubo cardiomyopathy. This report describes a singular case of Takotsubo cardiomyopathy precipitated by delirium tremens in a cirrhotic patient with acute-on-chronic liver failure.

Clinical significance of optical coherence tomography-guided angioplasty on treatment selection.

The present study aimed to observe whether optical coherence tomography (OCT)-guided angioplasty is able to provide useful clinical information beyond that obtained by angiography as well as provide recommendations for physicians that may improve treatment selection. This prospective study included 83 patients with coronary artery disease (>18 years) undergoing coronary angiography (CAG) for ST-elevation myocardial infarction (n=13), non-ST-elevation myocardial infarction (n=19), stable angina (n=22), unstable angina (n=10), silent ischemia (n=11), or elective percutaneous coronary intervention (n=8). Following the initial CAG (CAG-pre), the patients underwent OCT before angioplasty (OCT-pre, 24 patients), after angioplasty (OCT-post, 22 patients), or both (37 patients). The thrombus burden, calcification and plaque dissection or rupture were compared between the OCT-pre and CAG-pre recordings. Following angioplasty, stent malapposition, suboptimal stent deployment, suboptimal stent lesion coverage, and edge dissection were compared between OCT-post and CAG-post alone. Among the 83 patients, 45.7% had single-vessel and 54.3% had multiple-vessel disease. OCT pre- and post-angioplasty revealed significantly more information on the procedure than CAG alone. This clinical information changed the clinical strategies in 41/83 (49.4%) patients, including 58 modifications of therapeutic strategy (69.9%, 58/83): Thrombus aspiration in 2 cases (2.4%), administration of glycoprotein IIb/IIIa inhibitors in 8 cases (9.6%), additional balloon inflation in 23 cases (27.7%), additional stent implantation in 17 cases (20.5%), avoiding stent implantation in 4 cases (4.8%), collateral intervention in 2 cases (2.4%), and guidewire reposition in 2 cases (2.4%). In conclusion, OCT-pre and OCT-post provided additional clinical information beyond that obtained by angiography alone, which resulted in modification of the treatment strategies in half of the included patients.

Incidence, Predictors, and Impact on Six-Month Mortality of Three Different Definitions of Contrast-Induced Acute Kidney Injury After Coronary Angiography.

We assessed incidence, predictors, and impact on 6-month mortality of contrast-induced acute kidney injury (CI-AKI) after coronary angiography with or without percutaneous coronary intervention in patients with acute coronary syndrome (ACS), according to 3 different CI-AKI definitions. Serum creatinine (sCr) was assessed at baseline and 48 to 72 hours after procedure to classify patients into 3 CI-AKI groups: Group 1: increase in sCR ≥25% over baseline but absolute increase <0.5 mg/dl; Group 2: absolute increase ≥0.5 mg/dl; Group 3: absolute increase ≥0.3 mg/dl or ≥50% over baseline. The association between CI-AKI and all-cause 6-month mortality was assessed using multivariate Cox regression. Among 1,002 patients included, median age was 68 [57 to 79] years. The sample had the following characteristics: 70% men, 25% diabetics, 22% had a history of myocardial infarction, 21% had baseline estimated glomerular filtration rate (as calculated by the Modification of Diet in Renal Disease) <60 ml/min/1.72 m2, 34% had ST-segment elevation myocardial infarction, 61% underwent percutaneous coronary intervention, and 43% had multivessel disease. Based on changes in sCr, 89 patients (8.9%) were classified in Group 1; 69 (6.9%) in Group 2; and 157 (15.7%) in Group 3, whereas sCr did not increase >25% in the remaining 844 (84.2%). CI-AKI was significantly associated with 6-month all-cause mortality using the definitions for Group 2 (hazard ratio 3.1, 95% confidence interval [CI] 1.5 to 6.6, p = 0.002) and Group 3 (hazard ratio 2.03, 95% CI 1.03 to 4.0, p = 0.04), but not Group 1. In conclusion, based on the definition used for CI-AKI, CI-AKI is observed in 6% to 15.7% of patients. An increase of 25% over baseline sCr does not identify high-risk patients. CI-AKI defined as an increase in sCr >0.3 mg/dl identifies 15.7% of the population at 2-fold higher risk of mortality.

Detection of Residual Pulmonary Vascular Obstruction by Ventilation-Perfusion Lung Scan Late After a First Pulmonary Embolism.

The long-term impact of persistent pulmonary vascular obstruction after pulmonary embolism (PE) remains unknown. Based on ventilation-perfusion lung scan performed at discharge and 3 months after a first PE, we aimed to investigate the prognostic value on 5-year adverse events of (1) residual pulmonary vascular obstruction (RPVO) at discharge (DIS-RPVO), (2) RPVO at 3 months (3M-RPVO), and (3) relative change in RPVO between the 2 scans (RC-RPVO). We performed a prospective, multicenter cohort study from January 2007 to December 2009 including patients who survived at least 3 months after a PE. RC-RPVO was defined as (DIS-RPVO - 3M-RPVO)/DIS-RPVO. The primary end point was a combined end point at 5 years, composed of all-cause death, recurrent venous thromboembolism, chronic thromboembolic pulmonary hypertension, heart failure, and rehospitalization for cardiac causes. Receiver-operating characteristic curves were computed to define thresholds of DIS-RPVO, 3M-RPVO, and RC-RPVO predictive of the primary combined end point at 5 years. Overall, 241 patients were included (high-risk PE: 11.2%, intermediate-risk PE: 51.8%, low-risk PE: 37%). Mean DIS-RPVO was 27.9 ± 15.1%, mean 3M-RPVO was 10.3 ± 10.8%, and mean RC-RPVO was 61.7 ± 33.4%. At 5 years, 112 patients (46.5%) experienced the combined end point. Both 3M-RPVO ≥15% and RC-RPVO ≤37.5% were independently related to the occurrence of the combined end point at 5 years (p = 0.01 and p = 0.02, respectively). DIS-RPVO did not predict long-term adverse events. In conclusion, RC-RPVO ≤37.5% and 3M-RPVO ≥15% were independently related to the occurrence of adverse events 5 years after a first PE.

Effect of Fractional Flow Reserve (≤0.90 vs >0.90) on Long-Term Outcome (>10 Years) in Patients With Nonsignificant Coronary Arterial Narrowings.

We assessed the long-term (>10 years) clinical course of patients with documented coronary lesions deemed nonsignificant according to fractional flow reserve (FFR) assessment and investigated whether the initial FFR value impacted on prognosis. From January 2000 to October 2003, all patients submitted to coronary angiography with FFR measurement were included in a single-center, prospective registry. Patients with an FFR value >0.80 were treated medically without revascularization. Major adverse cardiac events (MACE) (death, acute coronary syndrome (ACS), or coronary revascularization) were compared according to initial FFR value (absolute value and by category, ≤0.90 vs >0.90). Analyses were performed using a multivariable Cox model and propensity score matching. Among 257 patients (332 lesions) treated medically initially, 131 (51%, 143 lesions) had FFR ≤0.90 and 126 (49%, 189 lesions) >0.90. During follow-up (median duration, 11.6 years), 82 (31.9%) had a MACE, 38 (14.8%) died, 17 (6.6%) had ACS, 93 (36.2%) had repeat coronary angiography, and 27 (10.5%) had revascularization. There was no clinical, biologic or angiographic difference between patients with initial FFR value ≤0.90 versus >0.90. Adjusted Cox model showed no difference in relative risk of MACE, death, ACS, or revascularization. Coronary angiographies were numerically more frequent in patients with FFR ≤0.90, versus FFR >0.90. These findings were confirmed by propensity score-matched comparison. In patients with coronary narrowings left unrevascularized based on FFR, an FFR value between 0.80 and 0.90 has no impact on long-term outcome compared with those with FFR >0.90. In conclusion, patients with high FFR values should not be considered as having a lower risk of coronary event.