A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

Cardiac resynchronization in Poland - comparable procedural routines? Insights from CRT Survey II.

INTRODUCTION: CRT Survey II was initiated by the European Heart Rhythm Association and the Heart Failure Association, to explore everyday implantation practice of cardiac resynchronization therapy (CRT) devices in a broad spectrum of hospitals in European Society of Cardiology (ESC) member countries. AIM: To compare Polish and European procedural practice. MATERIAL AND METHODS: Procedural details of Polish patients collected in 37 Polish centres (n = 1241 - Poland group) were compared to the patients enrolled throughout Europe (n = 9847 - CRT II Survey group). RESULTS: There were significant differences in: successful implantation (96.1% vs. 97.4%), type of device implanted (for CRT-D: 87% vs. 67.6%), implanting physician subspecialty (for electrophysiologist: 69.2% vs. 79.8%), type of location of procedure (for operating room: 19.4% vs. 8.9%), duration of procedure (117.8 ±44 vs. 97.5 ±46.1 min), left ventricle lead type (for multipolar lead: 50% vs. 57.9%), coronary sinus venogram with occlusion rate (41.4% vs. 47.9%) and peri-procedural complication rate (7.5% vs. 5.3%) between Poland and CRT II Survey groups, respectively. CONCLUSIONS: This study provides important information describing current differences in Polish procedural routines in relation to ESC member countries. Heterogeneous CRT implantation practices across European countries still exist. However, it may be related to different clinical profile of patients qualified for CRT implantation in Poland as well as organization of care.

Impella LD microaxial pump supporting combined mitral and coronary surgery in a patient with dilated cardiomyopathy. A short bridge to recovery?

Cardiac surgeons have to face the problem of impaired left ventricle function in patients undergoing routine valve or coronary procedures. The intra-aortic balloon pump is not always effective in preventing cardiac failure. The idea of using a microaxial rotating pump as a short-term perioperative support seems to be a convenient solution. The case of a patient with dilated cardiomyopathy undergoing combined mitral and coronary surgery with elective use of the Impella LD pump is presented. Various options of applying the Impella device are discussed, especially as a bridge to transplant or bridge to recovery.

Defibrillator implantation early after myocardial infarction.

BACKGROUND: The rate of death, including sudden cardiac death, is highest early after a myocardial infarction. Yet current guidelines do not recommend the use of an implantable cardioverter-defibrillator (ICD) within 40 days after a myocardial infarction for the prevention of sudden cardiac death. We tested the hypothesis that patients at increased risk who are treated early with an ICD will live longer than those who receive optimal medical therapy alone. METHODS: This randomized, prospective, open-label, investigator-initiated, multicenter trial registered 62,944 unselected patients with myocardial infarction. Of this total, 898 patients were enrolled 5 to 31 days after the event if they met certain clinical criteria: a reduced left ventricular ejection fraction (< or = 40%) and a heart rate of 90 or more beats per minute on the first available electrocardiogram (ECG) (criterion 1: 602 patients), nonsustained ventricular tachycardia (> or = 150 beats per minute) during Holter monitoring (criterion 2: 208 patients), or both criteria (88 patients). Of the 898 patients, 445 were randomly assigned to treatment with an ICD and 453 to medical therapy alone. RESULTS: During a mean follow-up of 37 months, 233 patients died: 116 patients in the ICD group and 117 patients in the control group. Overall mortality was not reduced in the ICD group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.35; P=0.78). There were fewer sudden cardiac deaths in the ICD group than in the control group (27 vs. 60; hazard ratio, 0.55; 95% CI, 0.31 to 1.00; P=0.049), but the number of nonsudden cardiac deaths was higher (68 vs. 39; hazard ratio, 1.92; 95% CI, 1.29 to 2.84; P=0.001). Hazard ratios were similar among the three groups of patients categorized according to the enrollment criteria they met (criterion 1, criterion 2, or both). CONCLUSIONS: Prophylactic ICD therapy did not reduce overall mortality among patients with acute myocardial infarction and clinical features that placed them at increased risk. (ClinicalTrials.gov number, NCT00157768.)

Late ventricular remodeling in non-reperfused acute myocardial infarction in humans is predicted by angiotensin II type 1 receptor density on blood platelets.

BACKGROUND: Ventricular remodeling after myocardial infarction (MI) is largely dependent on renin-angiotensin system activity, which is determined by angiotensin II concentration and angiotensin II type 1 receptor (AT(1)R) density in target tissues. We have recently shown that AT(1)R density in the acute phase of MI determines post-MI ventricular remodeling at discharge (8 days). The aim of this study was to test whether this correlation is retained in a longer follow-up (6 months), in the same group of patients. METHODS: In 48 patients with first acute MI who did not undergo reperfusion therapy, angiotensin AT(1)R density on blood platelets (a presumable marker of cardiovascular AT(1)R density) was assessed 13+/-5 h after the onset of MI, using radioligand binding assay. Echocardiographic indices of left ventricular function and dimensions were used as measures of ventricular remodeling. RESULTS: 6 months after the infarction patients who at baseline had AT(1)R density above median (N=17) as compared to those with AT(1)R density below median (N=20) had higher left ventricular end-systolic volume index (LVESVI, 41.3+/-2.7 vs. 33.2+/-2.3) and lower ejection fraction (LVEF 48.1+/-1.8 vs. 54.7+/-2.0). Moreover LVESVI positively and LVEF negatively correlated with AT(1)R density although the strength of these correlations was weaker than at discharge. Infarct size as reflected by a single troponin T measurement and post-MI therapy did not differ between high- and low-AT(1)R groups: over 85% patients received ACE-inhibitor, beta-blocker and statin. CONCLUSIONS: High AT(1)R density on blood platelets (a presumable marker of cardiovascular AT(1)R density) drawn in the acute phase of MI predicts poorer left ventricular systolic function in 6-month follow up. This suggests that modern therapy offers suboptimal blockade of renin-angiotensin system activity in the setting of MI.

Angiotensin II AT1 receptor density on blood platelets predicts early left ventricular remodelling in non-reperfused acute myocardial infarction in humans.

BACKGROUND: Renin-angiotensin-system activity, a principal factor determining ventricular remodelling after myocardial infarction (MI), is dependent on local angiotensin II concentration and angiotensin AT1 receptor (AT1R) density. The latter is regulated by systemic factors acting independently from angiotensin II concentration. OBJECTIVE: To test the hypothesis that AT1R density at the onset of MI determines post-MI ventricular remodelling. METHODS: In 48 patients with first acute MI who did not undergo reperfusion therapy, angiotensin AT1R density on blood platelets (reflecting cardiovascular AT1R density) was assessed 13+/-5 h after the onset of MI, using radioligand binding assay. Left ventricular end-systolic (LVESVI) and end-diastolic volume indices (LVEDVI) and ejection fraction (EF) were assessed by two-dimensional echocardiography as measures of ventricular remodelling. RESULTS: Predischarge LVESVI and LVEDVI positively and EF negatively correlated with AT1R density. Patients with AT1R density below median had significantly lower LVESVI (33.2+/-2.4 mL/m2), LVEDVI (70.0+/-2.8 mL/m2) and higher EF (52.8+/-2.3%) than patients with AT1R density above median (LVESVI = 44.9+/-2.6, LVEDVI = 81.3+/-3.9 mL/m2 and EF = 44.9+/-2.6%, all p<0.01). In multivariate analysis, only AT1R density and infarct size were independent predictors of early post-MI ventricular dilation. CONCLUSIONS: High density of AT1R at the onset of MI is a predictor of early left ventricular remodelling.

Effect of angiotensin-converting enzyme or vasopeptidase inhibition on ventricular size and function in patients with heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) echocardiographic study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition attenuates ventricular remodeling and improves ventricular function in heart failure patients. Vasopeptidase inhibition has shown similar effects in experimental models. OBJECTIVES: The OVERTURE echocardiographic study was designed to test the hypothesis that the vasopeptidase inhibitor omapatrilat would attenuate ventricular remodeling and improve ventricular function to a greater extent than an ACE inhibitor. METHODS: Three hundred twenty-one patients with heart failure (New York Heart Association class > or = 2) were included in the OVERTURE echocardiographic substudy and were randomized to receive enalapril (10 mg twice a day) or omapatrilat (40 mg every day). Echocardiograms were performed at baseline and at 1 year (n = 214). Left ventricular size was estimated by summation of ventricular areas in apical and short-axis views and by calculation of ventricular volumes. Ejection fraction was calculated from ventricular volumes. RESULTS: Combined diastolic and systolic areas and volumes decreased significantly (mean diastolic area change -8.36 cm2, 95% CI -9.4 to -7.3 cm2; mean systolic change -8.4 cm2, 95% CI -9.5 to -7.3 cm2), and ejection fractions increased significantly (3.6%, 95% CI 2.6% to 4.6%) in both treatment groups from baseline to 1 year. There were no differences in the magnitude of improvement in ventricular size or function based on treatment assignment. Patients who died or were hospitalized for heart failure subsequent to the final assessment demonstrated the least degree of reverse remodeling. CONCLUSION: Ventricular size and function improved similarly after 1 year with ACE or vasopeptidase inhibition in patients with heart failure. Reverse remodeling was associated with improved outcome.

Clinical performance of automatic closed-loop stimulation systems.

Inos pacemakers use contraction dynamics to regulate the pacing rate according to the Closed-Loop Stimulation (CLS) principle. The physician can program only the lower and upper rate limits, while the internal rate responsive parameters are continually adjusted to changing patient conditions. Seventy-two patients with sinus node disease were enrolled in the multicenter Rate Behavior of the Pacing System Inos (2) CLS during Daily Life (RAPID) study to evaluate the appropriateness of CLS rates during daily activities and the long-term stability of the system. The pacemakers clearly differentiated between climbing stairs, descending stairs, and slow walking, with the corresponding peak rates of 104 +/- 18, 95 +/- 15, and 88 +/- 11 beats/min, respectively (P < 0.001 for any pair of activities). The peak CLS rate during the color-word test was significantly higher than that at rest (80 +/- 8 vs 67 +/- 7 beats/min, P = 0.002). The 24-hour heart rate trends retrieved from the pacemaker memory at 3, 6, and 12 months after implantation appeared appropriate in all patients except for two whose pacing rates were occasionally too fast during the night. Mean diurnal and nocturnal rates determined at 3-month, 6-month, and 12-month examinations fluctuated only slightly, from 74.6-75.3 beats/min (diurnal,P = NS) and from 67.0-68.1 beats/min (nocturnal,P = NS), indicating a satisfactory long-term stability of the system. The incidence of atrial pacing events during the entire follow-up was 82 +/- 18%. A 6.5-8.3 beats/min difference, on average, between day and night (P < 0.001)and distinction between different daily activities seem to evidence sensitivity of the automatic CLS-driven pacemakers to physiological demands despite minimum programming requirements.

Calcium blocker therapy before myocardial infarction increases post-infarction short- and long-term mortality. Data from the INJECT trial.

BACKGROUND: Short-acting calcium channel blockers (Ca-blockers) have been shown in some studies to increase the risk of myocardial infarction (MI) and post-MI complications. Data from large, international, randomised studies such as the INJECT trial may bring new important information on the effects of medication used before MI, on the course of MI and post-MI complications. AIM: To assess the effects of beta-blocker and Ca-blocker therapy administered prior to MI on the early and late outcome after MI. METHODS: The study group consisted of 6001 patients with acute MI treated according to the INJECT protocol. The patients were divided into four groups according to the type of treatment before the index MI: Group I (n=580) - patients treated with beta-blockers; Group II (n=831) - patients treated with Ca-blockers; Group III (n=277) - patients treated with both beta-blockers and Ca-blockers; and Group IV (n=4313) - no beta-blocker or Ca-blocker treatment. The analysed end-points were 35- and 180-day mortality as well as angina recurrences, occurrence of heart failure, atrial fibrillation/flutter and asystole. RESULTS: During hospital stay, supraventricular arrhythmias, asystole, recurrent ischaemia and heart failure occurred more frequently in patients from groups II and III than in other groups. Early mortality was significantly higher in group II (p<0.001) and group III (p<0.002) than in group IV. Late mortality was the lowest in group IV, followed by group I. Cox proportional hazards multivariable analysis revealed that hypotension, Killip class IV (p<0.001), previous Ca-blocker (p<0.01) or Ca- and beta-blocker treatment (p<0.01) as well as previous MI (p<0.05) were the independent predictors of death. CONCLUSIONS: Compared with beta-blocker therapy or no treatment, previous use of Ca-blockers increases both early and long-term complication rates in patients with MI.