Sonothrombolysis before and after percutaneous coronary intervention provides the largest myocardial salvage in ST-segment Elevation Myocardial Infarction.

BACKGROUND: Sonothrombolysis is a therapeutic application of ultrasound with ultrasound contrast for patients with ST elevation Myocardial Infarction (STEMI). Recent trials demonstrated that sonothrombolysis, delivered before and after primary percutaneous coronary intervention (pPCI), increase infarct vessel patency, improve microvascular flow, reduce infarct size, and improve ejection fraction. However, it is unclear whether pre-pPCI sonothrombolysis is essential for therapeutic benefit. We designed a parallel three-arm sham-controlled randomised controlled trial to address this. METHODS: Patients presenting with first STEMI undergoing pPCI within six hours of symptom onset were randomised 1:1:1 into three arms: sonothrombolysis pre/post pPCI (Group 1), Sham pre & sonothrombolysis post pPCI (Group 2), and Sham pre/post pPCI (Group 3). Our primary endpoint was infarct size (% LV mass) assessed by Cardiac MRI at day 4±2. Secondary endpoints included myocardial salvage index (MSI) and echocardiographic parameters at Day 4±2 and six months. RESULTS: Our trial was ceased early due to the COVID pandemic. From 122 patients screened between September 2020 and June 2021, 51 patients (Age 60, male 82%) were included post randomisation. Median sonothrombolysis took 5 minutes pre pPCI and 15 minutes post, without significant door-to-balloon delay. There was a trend towards reduction in median infarct size between Group 1 (8%[IQR 4,11]), Group 2 (11%[7,19]) or Group 3 (15%[9,22]). Similarly there was a trend towards improved MSI in Group 1 (79%[64,85]) compared to Groups 2 (51%[45,70]) and 3 (48%[37,73]) No major adverse cardiac events occurred during hospitalization. CONCLUSION: Pre-pPCI sonothrombolysis may be key to improving MSI in STEMI. Multicentre trials and health economic analyses are required before clinical translation.

Adverse reactions of low osmolar non-ionic and ionic contrast media when used together or separately during percutaneous coronary intervention.

BACKGROUND: Due to perceived advantages in the use of non-ionic contrast agents for diagnostic angiography and ionic agents for percutaneous coronary intervention (PCI), patients often receive various combinations of both types of agents. AIM: To assess potential adverse effects of non-ionic and ionic contrast media when used together or separately during percutaneous coronary intervention. METHODS: We retrospectively evaluated the outcomes of 532 patients undergoing percutaneous coronary intervention in our institution. Patients were divided into two groups: those that underwent diagnostic angiography and "follow on" PCI; and those that underwent "planned" PCI. The groups were subdivided on the basis of the use of the ionic agent ioxaglate or the non-ionic agent iopromide during PCI. The frequency of allergic reactions and major adverse cardiac events (MACE) were noted. RESULTS: With respect to the "follow on" group, allergic reactions occurred in 9 of 150 patients (6.0%) who received the combination of ioxaglate and iopromide versus 1 of 93 (1.1%) who only received iopromide (p=0.094). There was no difference with respect to MACE [6 (4.0%) ioxaglate and iopromide versus 4 (4.3%) iopromide alone, p=1.00]. In the "planned" group, 7 of 165 patients (4.2%) receiving ioxaglate had an allergic reaction as opposed 0.0% (0 of 124 patients) in the iopromide group (p=0.021). All contrast reactions were mild. The incidence of a MACE was similar in both groups [1 (0.6%) ioxaglate versus 2 (1.6%) iopromide, p=0.579]. The incidence of allergic reactions was similar if ioxaglate was used alone or in combination with iopromide (p=0.478). CONCLUSIONS: Whilst combining ionic and non-ionic contrast agents in the same procedure was not associated with any more adverse reactions than using an ionic contrast agent alone, the ionic contrast agent ioxaglate was associated with the majority of allergic reactions. With respect to choice of contrast agent, using the non-ionic agent iopromide alone for coronary intervention is associated with the lowest risk of an adverse event.

A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after coronary stent implantation.

BACKGROUND: The combination of a thienopyridine and aspirin has become the standard of care after intracoronary stenting. Clopidogrel appears to be better tolerated than ticlopidine but may be associated with more adverse cardiac events. We assessed the tolerability and efficacy of 2 weeks of therapy with ticlopidine and aspirin in comparison to clopidogrel and aspirin after coronary stent implantation. METHODS: Patients with successful intracoronary stent implantation at our institution were randomly assigned, in addition to aspirin, to receive either ticlopidine or clopidogrel. Loading doses were administered immediately after the procedure, and the drugs were continued for 2 weeks. RESULTS: Three hundred seven patients were randomly assigned: 154 patients to clopidogrel and 153 to the ticlopidine group. The primary end point of early drug discontinuation occurred in 5 patients (3.3%) in the ticlopidine group and 1 patient (0.6%) in the clopidogrel group (P =.121). Within 30 days, thrombotic stent occlusion occurred in 1 patient (0.7%) in the ticlopidine group and 3 patients (1.9%) in the clopidogrel group (P =.623). A major adverse cardiac event occurred in 3 patients (approximately 1.9%; P = 1.00) in each group. CONCLUSIONS: There was a nonsignificant trend to improved tolerability of a 2-week regimen of clopidogrel and aspirin when compared with ticlopidine and aspirin in patients undergoing intracoronary stent implantation. The combination of clopidogrel and aspirin results in a comparably low incidence of major adverse cardiac events when compared with ticlopidine and aspirin.

Dietary cholesterol alters Na+/K+ selectivity at intracellular Na+/K+ pump sites in cardiac myocytes.

A modest diet-induced increase in serum cholesterol in rabbits increases the sensitivity of the sarcolemmal Na+/K+ pump to intracellular Na+, whereas a large increase in cholesterol levels decreases the sensitivity to Na+. To examine the mechanisms, we isolated cardiac myocytes from controls and from rabbits with diet-induced increases in serum cholesterol. The myocytes were voltage clamped with the use of patch pipettes that contained osmotically balanced solutions with Na+ in a concentration of 10 mM and K+ in concentrations ([K+]pip) ranging from 0 to 140 mM. There was no effect of dietary cholesterol on electrogenic Na+/K+ current (Ip) when pipette solutions were K+ free. A modest increase in serum cholesterol caused a [K+]pip-dependent increase in Ip, whereas a large increase caused a [K+]pip-dependent decrease in Ip. Modeling suggested that pump stimulation with a modest increase in serum cholesterol can be explained by a decrease in the microscopic association constant KK describing the backward reaction E1 + 2K+ --> E2(K+)2, whereas pump inhibition with a large increase in serum cholesterol can be explained by an increase in KK. Because hypercholesterolemia upregulates angiotensin II receptors and because angiotensin II regulates the Na+/K+ pump in cardiac myocytes in a [K+]pip-dependent manner, we blocked angiotensin synthesis or angiotensin II receptors in vivo in cholesterol-fed rabbits. This abolished cholesterol-induced pump inhibition. Because the epsilon-isoform of protein kinase C (epsilonPKC) mediates effects of angiotensin II on the pump, we included specific epsilonPKC-blocking peptide in patch pipette filling solutions. The peptide reversed cholesterol-induced pump inhibition.

Chronic amiodarone-induced inhibition of the Na+-K+ pump in rabbit cardiac myocytes is thyroid-dependent: comparison with dronedarone.

OBJECTIVE: To examine the thyroid-dependence of the effect of amiodarone on the sarcolemmal Na(+)-K(+) pump, and the effect on the pump of dronedarone, a deiodinated amiodarone congener without influence on thyroid status. METHODS: New Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na(+)-K(+) pump current was measured using the whole-cell patch-clamp technique in isolated ventricular myocytes. Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks. RESULTS: Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT(c). However, it had no effect on Na(+)-K(+) pump current. CONCLUSIONS: The inhibitory effect of amiodarone on Na(+)-K(+) pump current is thyroid-dependent, whereas the effects on heart rate and QT(c) are at least partially mediated by thyroid-independent mechanisms. In contrast to its parent compound, dronedarone has no significant effects on the activity of the Na(+)-K(+) pump.