Lifestyle Walking Intervention for Patients With Heart Failure With Reduced Ejection Fraction: The WATCHFUL Trial.

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

Catheter ablation of atrial fibrillation and atrial tachycardia in patients with pulmonary hypertension: a randomized study.

AIMS: Atrial fibrillation (AF), typical atrial flutter (AFL), and other atrial tachycardias (ATs) are common in patients with pulmonary hypertension. Frequently, several supraventricular arrhythmias are successively observed in individual patients. We investigated the hypothesis of whether more extensive radiofrequency catheter ablation of the bi-atrial arrhythmogenic substrate instead of clinical arrhythmia ablation alone results in superior clinical outcomes in patients with pulmonary arterial hypertension (PH) and supraventricular arrhythmias. METHODS AND RESULTS: Patients with combined post- and pre-capillary or isolated pre-capillary PH and supraventricular arrhythmia indicated to catheter ablation were enrolled in three centres and randomized 1:1 into two parallel treatment arms. Patients underwent either clinical arrhythmia ablation only (Limited ablation group) or clinical arrhythmia plus substrate-based ablation (Extended ablation group). The primary endpoint was arrhythmia recurrence >30 s without antiarrhythmic drugs after the 3-month blanking period. A total of 77 patients (mean age 67 ± 10 years; 41 males) were enrolled. The presumable clinical arrhythmia was AF in 38 and AT in 36 patients, including typical AFL in 23 patients. During the median follow-up period of 13 (interquartile range: 12; 19) months, the primary endpoint occurred in 15 patients (42%) vs. 17 patients (45%) in the Extended vs. Limited ablation group (hazard ratio: 0.97, 95% confidence interval: 0.49-2.0). There was no excess of procedural complications and clinical follow-up events including an all-cause death in the Extended ablation group. CONCLUSION: Extensive ablation, compared with a limited approach, was not beneficial in terms of arrhythmia recurrence in patients with AF/AT and PH. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT04053361.

Arterial Hypertension and Risk of Recurrent Event in Young Ischemic Stroke Patients.

INTRODUCTION: In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients. METHODS: The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification. RESULTS: Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510-24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000). CONCLUSION: AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.

Young cryptogenic ischemic stroke: A descriptive analysis of clinical and laboratory characteristics, outcomes and stroke recurrence.

BACKGROUND AND PURPOSE: Ischemic strokes (IS) occur also in young adults and despite an extensive work-up the cause of IS remains very often cryptogenic. Thus, effectiveness of secondary prevention may be unclear. We aimed to analyze a relationship among vascular risk factors (VRF), clinical and laboratory parameters, outcomes and recurrent IS (RIS) in young cryptogenic IS (CIS) patients. SUBJECTS AND METHODS: The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). All analyzed patients underwent transesophageal echocardiography, 24-h and 3-week ECG-Holter to assess cause of IS according to the ASCOD classification. Recurrent IS (RIS) was recorded during a follow-up (FUP). RESULTS: Out of 294 young enrolled patients, 208 (70.7%, 113 males, mean age 41.6 ± 7.2 years) were identified as cryptogenic. Hyperlipidemia (43.3%), smoking (40.6%) and arterial hypertension (37.0%) were the most frequent VRF. RIS occurred in 7 (3.4%) patients during a mean time of FUP 19 ± 23 months. One-year risk of RIS was 3.4% (95%CI: 1.4-6.8%). Patients with RIS were older (47.4 vs. 41.1 years, p = 0.007) and more often obese (71.4 vs. 19.7%, p = 0.006), and did not differ in any of other analyzed parameters and VRF. Multivariate logistic regression analysis showed obesity (OR: 9.527; 95%CI: 1.777-51.1) and the previous use of antiplatelets (OR: 15.68; 95%CI: 2.430-101.2) as predictors of recurrent IS. CONCLUSION: Despite a higher presence of VRF in young CIS patients, the risk of RIS was very low. Obesity and previous use of antiplatelet therapy were found the only predictors of RIS.

Macitentan in pulmonary hypertension due to left ventricular dysfunction.

The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI -15.07-33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12, versus placebo, the macitentan group showed no change in PVR, mean right atrial pressure or pulmonary arterial wedge pressure; a non-significant increase in cardiac index (treatment effect 0.4 (95% CI 0.1-0.7) L·min-1·m-2) and decrease in NT-proBNP (0.77 (0.55-1.08)) was observed. Adverse events and serious adverse events were numerically more frequent with macitentan versus placebo.Macitentan-treated patients were quantitatively more likely to experience significant fluid retention versus placebo. Macitentan resulted in no significant changes in any exploratory end-points.

Patent Foramen Ovale and the Risk of Cerebral Infarcts in Acute Pulmonary Embolism-A Prospective Observational Study.

BACKGROUND: Pulmonary embolism (PE) is associated with a risk of consecutive paradoxical embolism with brain infarction through a patent foramen ovale (PFO). The aims of this study were to assess the rate of new ischemic brain lesions (IBLs) using magnetic resonance imaging (MRI) during a 12-month follow-up period with anticoagulation and to evaluate the potential relationship with the presence of PFO on transesophageal echocardiography (TEE). SUBJECTS AND METHODS: Seventy-eight patients with acute PE underwent baseline contrast TEE with brain MRI. After the 12-month follow-up, 58 underwent brain MRI. The rates of MRI documenting new IBLs were measured based on the presence of PFO. RESULTS: PFO was detected in 31 patients (39.7%). At baseline MRI, IBL was present in 39 of 78 patients (50%). The presence of IBL was not significantly higher in patients with PFO than in patients without PFO (20 [64.5% patients with PFO] versus 19 [40.4% without PFO] of 39 patients with baseline IBL, P = .063). At the follow-up MRI, in the group with new IBL (9 of 58 patients, 15.5%), the number of patients with PFO was significantly higher than that without PFO (7 [33.3%] versus 2 [5.4%], P = .008). PFO was identified as an independent predictor of new IBL (odds ratio 4.6 [1.6-47.4], P = .008). CONCLUSIONS: The presence of PFO was associated with new IBL in patients with PE. These patients are at a higher risk of ischemic stroke despite effective anticoagulation therapy.

Polymorphism of the Fcγ Receptor II as a Possible Predisposing Factor for Heparin-Induced Thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. However, only a portion of the antibodies have the ability to activate platelets, and these can be identified by a platelet aggregation test (functional testing). However, this expression has been detected to have a molecular cause, which is a mutation of FcγRIIa. The FcγRIIa receptor is responsible for the activation of platelets by antibodies in HIT. METHODS: To determine HIT, impedance aggregometry using the Multiplate analyzer (MEA) as heparin-induced aggregation technique and the Technozym HIT IgG ELISA test were used. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5 IU/mL. The results were compared with the ELISA test. Mutation of FcγRHa was assessed using the asymmetric real-time PCR method that is based on the reaction with two hybridization probes and melting curve analysis. RESULTS: Examined were 100 patients at a clinically intermediate and higher risk of HIT according to the 4T's score. All samples were examined by the ELISA test and MEA, with positive samples being further confirmed by high-concentration heparin. In the group of patients, 10.0% were positive by MEA as compared with 4% determined by ELISA. The results of genetic analysis of FcγRIIa did not provide statistically significant differences between positive patients found by the functional test as well as the ELISA test and seronegative patients. CONCLUSIONS: The genetic mutation FcγRIIa is a predisposing factor for manifestation of HIT in the form of thrombocytopenia, but the process of seroconversion apparently needs another inducing factor. Therefore, the examination of mutations can be classified as predisposing factors rather than to confirm the diagnosis of HIT.

Atrial fibrillation in young ischemic stroke patients: an underestimated cause?

BACKGROUND: Undetected atrial fibrillation (AF) is often suspected as the possible cause in patients with cryptogenic ischemic stroke (IS), especially in elderly population. In young IS patients, the prevalence of AF, particularly paroxysmal form, remains still not enough established. Our aim was to assess the presence of AF in young patients using a long-term electrocardiography (ECG) Holter monitoring. METHODS: The study set consisted of acute IS patients ≤50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study (NCT01541163). In all patients, admission ECG, serum cardiac markers, transesophageal echocardiography, 24-h and 3-week ECG Holter monitoring were performed. RESULTS: Out of 634 enrolled patients in the HISTORY study, 98 were ≤50 years (56 males, mean age 39.7 ± 8.4). In total, AF was detected in 10.2% of patients and 70% of them had a paroxysmal form of AF. The elevated serum cardiac markers were present in 70% of patients with detected AF (p = 0.0001). CONCLUSION: AF was detected in 10.2% of young stroke patients and paroxysmal form of AF prevailed. Using of long-term ECG Holter monitoring improved the detection of AF. Patients with presence of AF had more frequently elevated serum specific cardiac markers.

Changing Views: Safety and Efficacy of Implantable Cardioverter- Defibrillator Therapy in Athletes.

The implantable cardioverter-defibrillator (ICD) is highly effective in reducing sudden death from ventricular tachyarrhythmia among high-risk cardiac patients. Conventional advice given to patients with ICD is to avoid physical activity more strenuous than playing golf or bowling. This recommendation is given due to a theoretical risk of arrhythmia precipitation, and thus increased risk of death due to failure to defibrillate, injury resulting from loss of control caused by arrhythmia-related syncope or shock, and also due to sport related direct damage to the ICD system. Recent prospective data from an international registry involving 372 athletes with ICDs in situ and actively participating in sports has been published. This indicates that, although physical activity resulted in an increased number of shocks compared to rest, there was no significant difference between intensive physical activity and any other activity (10% vs. 8%, p=0.34) in frequency of shocks. Furthermore, over a median follow-up period of 31 months (21-46 months), in the period of sports activity and 2 hour rest directly after there were no occurrences of death, resuscitated arrest or arrhythmia, or shock-related injury. This data is likely to start a shift in every-day clinical decision-making leading to revision of the high level of precautions imposed on the rapidly enlarging ICD recipient population.

[Embolic ischemic strokes]. / Embolizacní ischemické cévní mozkové príhody.

Treatment of acute phase of ischemic stroke is aimed to limit the amount of damage using reperfusion strategy and subsequently administration of treatment providing pharmacological secondary prevention of recurrence. The early aetiology diagnosis of stroke is crucial for effective secondary prevention as the highest risk of recurrence is within few weeks after stroke. Exclusion of cardiac and vascular source of embolism by imaging methods is an important part in management of patients with ischemic stroke. These embolic sources are categorized as high risk and states are associated with moderate or unclear risk.

Impact of prior oral anticoagulation on admission stroke severity in patients with atrial fibrillation.

BACKGROUND AND AIMS: In patients with atrial fibrillation, oral anticoagulation therapy is indicated for both primary and secondary prevention of stroke/systemic embolism. Though direct oral anticoagulants with greater safety and efficacy than warfarin were introduced into clinical practice at the beginning of the last decade, even now not all patients with AF have adequate preventative anticoagulant treatment. The primary goal of this study was to evaluate the impact of prior use of oral anticoagulants on admission stroke severity in those with AF. Other aims were, inter alia, to assess the trend in atrial fibrillation prevalence in the years of the HISTORY trials 2012-2021 carried out in the Czech Republic and use of oral anticoagulants (OAC) in ischemic stroke (IS) patients. METHODS: We analyzed consecutive ischemic stroke patients who had been enrolled in the HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (identifier NCT01541163) in the year 2012 and carried out a yearly comparison (detailed in the text). RESULTS: In total, there were 1059 patients (55.9% males, mean age 71.7±12.8). There was no significant difference over the time period in rate of known (18.3 vs. 16.5%, P=0.442) or newly detected AF (17.0 vs. 16.0%, P=0.665), but sigificantly more patients with known AF were treated with oral anticoagulants before IS in the year 2021 (32.1 vs. 70.7%, P<0.0001), and direct oral anticoagulants (3.6 vs. 35.4%, P<0.0001). The number of patients with atrial fibrillation had not changed significantly over the years (26.2 vs. 31.3%). Patients on OAC had a lower median admission score on the National Institutes of Health Stroke Scale (NIHSS) than those not using an oral anticoagulant (6 vs. 16, P=0.0004) in 2021. CONCLUSIONS: There was no significant upward trend in atrial fibrillation in stroke patients admitted between 2012 and 2021, but patients with known AF were significantly more frequently treated with oral anticoagulants and direct oral anticoagulants (DOAC) in 2021. Patients on OAC had lower admission NIHSS scores than those not using any anticoagulent in the year 2021. The difference in the median admission NIHSS between the patients on OAC and those without OAC treatment was not significant in the year 2012 (6 vs. 12, P=0.066). This might be related to the fact that substantially fewer patients in 2012 were on DOACs, which are considered more effective than warfarin.

Comparison of myocardial perfusion study and invasive hemodynamic measurement of the significance of non-infarct-related residual stenoses in ST elevation myocardial infarction patients.

BACKGROUND: Nearly 50% of ST elevation myocardial infarction (STEMI) patients have multivessel coronary artery disease. The optimal selection of non-culprit lesions for complete revascularization is a matter of current debate. Little is known about the predictive value of myocardial perfusion study (MPS) in this scenario. METHODS: We enrolled 49 STEMI patients (61.5 ± 10.3 years) with at least one major non-culprit lesion (50-90%) other than left main coronary artery lesions. Overall 63 non-infarct- related artery (IRA) stenoses (65.2 ± 11.9%) were recommended for further evaluation using Fractional Flow Reserve (FFR) measurement as is standard in our institution. Prior to FFR, all patients were scheduled for non-invasive MPS using single-photon emission computed tomography (SPECT). Both FFR and MPS were performed 4-8 weeks after STEMI with MPS preceding FFR within no more than 48 hours. An FFR value of ≤0.80 was considered significant and guided the final revascularization strategy. The results of MPS were correlated to FFR as well as to the clinical and angiographic characteristics of both culprit and non-infarct-related lesions. RESULTS: Based on FFR, 30 out of 63 stenoses (47.6%) in 27 patients were considered hemodynamically significant (FFR 0.69 ± 0.08, range 0.51-0.79) compared to residual 33 stenoses considered negative (FFR 0.87 ± 0.04, range 0.81-0.96). The MPS revealed abnormal myocardium (23.6% average, range 5-56%) in 21 patients (42.8%). Among those patients, only 9 showed the evidence of ischemic myocardium (average 10.8%, range 4-18%) with low sensitivity of MPS in predicting positive FFR. Besides that, higher proportion of patients (71.4% vs. 42.9%, P=0.047) with overall lower FFR values (0.73 vs. 0.80, P=0.014, resp.) in non-IRAs as well as higher proportion of patients with more severely compromised flow in IRAs (P=0.048) during STEMI had MPS-detected abnormal myocardium. CONCLUSION: In STEMI patients with multivessel coronary artery disease, we observed rather weak correlation between MPS using SPECT and invasive hemodynamic measurement using FFR in ischemia detection.

Safety and efficacy of cangrelor, an intravenous, short-acting platelet inhibitor in patients requiring coronary artery bypass surgery.

OBJECTIVE: Oral P2Y12 platelet receptor inhibitors are a cornerstone of reducing complications in patients with acute coronary syndromes or coronary stents. Guidelines advocate discontinuing treatment with P2Y12 platelet receptor inhibitors before surgery. Cangrelor, a short-acting, reversible, intravenously administered P2Y12 platelet inhibitor is effective in achieving appropriate platelet inhibition in patients who are awaiting coronary artery bypass grafting (CABG) and require P2Y12 inhibition. The objective of this study was to assess the effects of preoperative cangrelor on the incidence of perioperative complications, which are currently unknown. METHODS: Patients (n = 210) requiring preoperative clinical administration of thienopyridine therapy were randomized in a multicenter, double-blinded study to receive cangrelor or placebo while awaiting CABG after discontinuation of the thienopyridine. Optimal platelet reactivity, which was defined as <240 P2Y12 platelet reaction units, was measured with serial point-of-care testing (VerifyNow). Pre- and postoperative outcomes, bleeding values, and transfusion rates were compared. To quantify potential risk factors for bleeding, we developed a multivariate logistic model. RESULTS: The differences between the groups in bleeding and perioperative transfusion rates were not significantly different. The rate of CABG-related bleeding was 11.8% (12/102) in cangrelor-treated patients and 10.4% (10/96) in the placebo group (P = .763). Transfusion rates for the groups were similar. Serious postoperative adverse events for the cangrelor and placebo groups were 7.8% (8/102) and 5.2% (5/96), respectively (P = .454). CONCLUSIONS: Compared with placebo, bridging patients with cangrelor prior to CABG effectively maintains platelet inhibition without increasing post-CABG complications, including bleeding and the need for transfusions. These data suggest cangrelor treatment is a potential strategy for bridging patients requiring P2Y12 receptor inhibition while they await surgery.

High incidence of acute and subacute ischaemic foci on brain MRI in patients with a diagnosis of acute pulmonary embolism and confirmed patent foramen ovale.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially life-threatening diagnosis when a certain amount of thrombotic mass obstructs blood flow through the pulmonary circulation. The finding of acute and subacute ischaemic foci on magnetic resonance imaging (MRI) of the brain in a group of patients with this diagnosis in whom we demonstrate the presence of patent foramen ovale (PFO) by transoesophageal echocardiography (TEE) is surprisingly high. METHODS: A total of 129 patients with a diagnosis of pulmonary embolism (confirmed by computed tomography with contrast agent, CTA) who consented to further examination were examined by transthoracic echocardiography (TTE) and transoesophageal echocardiography (TEE) with contrast agent, underwent magnetic resonance imaging of the brain according to a specific protocol, and underwent a comprehensive baseline laboratory examination. RESULTS: In our group of 129 patients, we found the presence of PFO in 36.4% (n=47) of them. A total of 5.4% (n=7) patients had asymptomatic acute and subacute ischaemic changes on brain MRI; 6 of them had concomitant PFO. The statistically significant correlation between troponin levels and the presence of pathological findings on MRI and the trend of a similar correlation for NT-proBNP values is also very interesting finding. CONCLUSIONS: The association between the presence of PFO and the occurrence of symptomatic or asymptomatic findings on brain MRI is a well-known fact (the issue of paradoxical embolism) but the high frequency of acute and subacute lesions on brain MRI in the group of patients with a diagnosis of acute PE is surprising.

Complete revascularization of multivessel coronary artery disease in patients with ST elevation acute coronary syndrome - for whom and when? A comprehensive review.

Atherosclerosis is the most common cause of coronary steno-occlusive disease and acute myocardial infarction is the leading cause of death in industrialized countries. In patients with acute ST elevation myocardial infarction (STEMI), there is unquestionable evidence that primary percutaneous coronary intervention providing recanalization of the infarct related artery (IRA) is the preferred reperfusion strategy. Nevertheless, up to 50% of patients with STEMI have multivessel coronary artery disease defined as at least 50% stenosis exclusive of IRA. There is conflicting data regarding the optimal treatment strategy and timing in such patients. Currently, it is assumed that stable patients might benefit from complete revascularization particularly in reducing the need for future unplanned procedures but only culprit lesion should be treated during index procedure in unstable patients. In this article, we provide a comprehensive overview of this important and currently highly debated topic.

Comparison of angiographic estimation and invasive hemodynamic measurement of the significance of non-infarct-related residual stenoses in ST-elevation myocardial infarction patients.

Introduction: Up to 50% of patients with ST elevation myocardial infarction (STEMI) have ≥ 50% stenosis in a major non-infarct-related artery. Several studies have evaluated the prognostic value of the completion of revascularization with overall inconclusive results. Selection of the stenoses was based on the angiographic evaluation, invasive hemodynamic measurement or the combined approach. It is unknown whether such a selection provides correlation of comparable patient groups. Material and methods: We enrolled 51 patients (62.7 ±10.2 years) with acute STEMI and at least one residual (50-90%) stenosis in a non-infarct-related major coronary artery (excluding left main coronary artery). Overall 65 stenoses (67.9 ±10.7%) were evaluated angiographically following primary percutaneous coronary intervention and the hemodynamic significance was estimated with respect to the stenosis severity, caliber of the arterial segment, localization of the stenosis (proximity) as well as the estimated size of the supplied vascular territory. During subsequent hospitalization, invasive measurement of the hemodynamic significance using fractional flow reserve (FFR) was performed to guide the final revascularization strategy (FFR value of ≤ 0.80 considered significant). Results: Based on angiographic evaluation, a total of 44 stenoses would be recommended for treatment, whereas only 31 stenoses were revascularized based on FFR measurement. Moreover, visual evaluation and hemodynamic measurement were discrepant in 27 of 65 (41.5%) stenoses. Conclusions: We observed a weak correlation between visual angiographic evaluation and invasive hemodynamic measurement. More stents would be implanted based on angiographic evaluation compared to FFR measurement.

Risk stratification using growth differentiation factor 15 in patients undergoing transcatheter aortic valve implantation.

AIMS: Growth differentiation factor 15 (GDF15) shows potential predictive value in various cardiac conditions. We investigated relationships between GDF15 and clinical or procedural outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) in order to propose clinically useful predictive risk stratification model. METHODS: This prospective single-center registry enrolled 88 consecutive patients with severe symptomatic aortic stenosis treated with TAVI. Clinical parameters were collected and biomarkers including GDF-15 were measured within 24 h before TAVI. All relevant clinical outcomes according to the Valve Academic Research Consortium-2 were collected over the follow-up period. RESULTS: The cohort included 52.3% of females. The mean age of study participants was 81 years; the mean Society of Thoracic Surgeons (STS) score and logistic EuroSCORE were 3.6% and 15.4%, respectively. The mortality over the entire follow-up period was 10.2%; no death was observed within the first 30 days following TAVI. Univariate analysis showed significant associations between GDF15 and mortality (P=0.0006), bleeding (P=0.0416) and acute kidney injury (P=0.0399). A standard multivariate logistic regression model showed GDF-15 as the only significant predictor of mortality (P=0.003); the odds ratio corresponding to an increase in GDF15 of 1000 pg/mL was 1.22. However, incremental predictive value was not observed when the STS score was combined with GDF15 in this predictive model. CONCLUSIONS: Based on our observations, preprocedural elevated GDF15 levels are associated with increased mortality and demonstrate their additional value in predicting adverse clinical outcomes in a TAVI population.

Determination of the prevalence and predictors of ventricular thrombus with assessment of the risk of systemic embolization to the CNS in patients after acute myocardial infarction using magnetic resonance imaging, echocardiography and cardiac markers - a prospective, unicentric, observational study.

BACKGROUND: Left ventricular thrombus (LVT) formation is one of the well-known and serious complications of acute myocardial infarction (AMI) due to the risk of systemic arterial embolization (SE). To diagnose LVT, echocardiography (TTE) is used. Late gadolinium-enhanced cardiovascular magnetic resonance (DE-CMR) is the gold standard for diagnosing LVT. OBJECTIVES: The aim of this observational study was to determine the role of transthoracic echocardiography and cardiac markers in predicting the occurrence of LVT compared with a reference cardiac imaging (DE-CMR) and to determine the risk of systemic embolization to the CNS using brain MRA. METHODS: Seventy patients after MI managed by percutaneous coronary intervention (localization: 92.9% anterior wall, 7% other; median age 58.7 years) were initially examined by transthoracic echocardiography (TTE, n=69) with a focus on LVT detection. Patients were then referred for DE-CMR (n=55). Laboratory determination of cardiac markers (Troponin T and NTproBNP) was carried out in all. Brain MRA was performed 1 year apart (n=51). RESULTS: The prevalence of LVT detected by echocardiography: (n=11/69, i.e. 15.9%); by DE-CMR: (n=9/55, i.e. 16.7%). Statistically significant parameters to predict the occurrence of LVT after AMI (cut off value): (a) detected by echocardiography: anamnestic data - delay (≥ 5 hours), echocardiographic parameters - left atrial volume index (LAVI≥ 32 mL/m2), LV EF Simpson biplane and estimated (≤ 42%), tissue Doppler determination of septal A wave velocity (≤ 7.5cm/s); (b) detected by DE-CMR: anamnestic data - delay (≥ 13 hours), DE-CMR parameters - left ventricular end-diastolic diameter (≥ 54mm). The value of cardiac markers (Troponin T and NTproBNP in ng/L) in LVT detected by echocardiography did not reach statistical significance. In LVT detected by DE-CMR, NTproBNP was statistically significantly increased at 1 month after AMI onset (no optimal cut-off value could be determined). There was no statistically significant association between the LVT detection (both modalities) and the occurrence of clinically manifest and silent cardioembolic events. CONCLUSION: Our study confirmed a relatively high prevalence of LVT in the high-risk group of patients with anterior wall STEMI. Due to the low prevalence of thromboembolic complications, no significant association between the LVT detection and the occurrence of a cardioembolic event was demonstrated.

Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial.

CONTEXT: Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding. OBJECTIVE: To evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery. DESIGN, SETTING, AND PATIENTS: Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery. MAIN OUTCOME MEASURES: The primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding. RESULTS: The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 µg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor. CONCLUSIONS: Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00767507.