A randomised trial of selective intracoronary hypothermia during primary PCI.

BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).

Transcatheter repair of massive primary mitral regurgitation: beyond the reach of the guidelines.

A 58-year-old male with prior history of mechanical aortic valve replacement (AVR) in 2009 for severe symptomatic aortic regurgitation in a bicuspid aortic valve, and since 2013 a new-onset severe asymptomatic primary mitral regurgitation (MR) due to prolapse of the anterior mitral valve leaflet (AMVL) presented himself with acute heart failure. Based on current guidelines recommendations, this patient was not eligible for transcutaneous mitral valve edge-to-edge repair (TEER), as well he was found as too high risk for conventional mitral valve repair. However, as a last resort TEER was undertaken with an unconventional strategy, which resulted in resolution of the MR and improvement of clinical, biochemical findings.

Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI.

OBJECTIVES: The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited. METHODS: The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed. RESULTS: In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50). CONCLUSIONS: Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.

Thermodilution-Based Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance: Quantification of Microvascular (Dys)Function?

During the last two decades, there has been a sharp increase in both interest and knowledge about the coronary microcirculation. Since these small vessels are not visible by the human eye, physiologic measurements should be used to characterize their function. The invasive methods presently used (coronary flow reserve (CFR) and index of microvascular resistance (IMR)) are operator-dependent and mandate the use of adenosine to induce hyperemia. In recent years, a new thermodilution-based method for measurement of absolute coronary blood flow and microvascular resistance has been proposed and initial procedural problems have been overcome. Presently, the technique is easy to perform using the Rayflow infusion catheter and the Coroventis software. The method is accurate, reproducible, and completely operator-independent. This method has been validated noninvasively against the current golden standard for flow assessment: Positron Emission Tomography-Computed Tomography (PET-CT). In addition, absolute flow and resistance measurements have proved to be safe, both periprocedurally and at long-term follow-up. With an increasing number of studies being performed, this method has great potential for better understanding and quantification of microvascular disease.

Intra-aortic balloon pump counterpulsation in extensive myocardial infarction with persistent ischemia: The SEMPER FI pilot study.

OBJECTIVES: This study aimed to prospectively investigate intra-aortic balloon pump counterpulsation (IABP) support in large myocardial infarction complicated by persistent ischemia after primary percutaneous coronary intervention (PCI). BACKGROUND: Use of IABP is suggested to be effective by increasing diastolic aortic pressure, thereby improving coronary blood flow. This can only be expected with exhausted coronary autoregulation, typical in acute myocardial infarction complicated by persistent ischemia. In this situation, augmented diastolic pressure is expected to increase myocardial oxygenation. METHODS: One hundred patients with large STEMI complicated by persistent ischemia after primary PCI were randomized to treatment with or without IABP therapy on top of standard care. IABP support was initiated following primary PCI, immediately after inclusion. Primary end point was all-cause mortality, need for (additional) mechanical hemodynamic support, or readmission for heart failure within 6 months. RESULTS: Mean age was 63 ± 10 years, 76% were male. Mean systolic and diastolic blood pressure were 120 ± 25 mmHg and 73 ± 17 mmHg. Mean heart rate was 75 ± 18 mmHg. Before PCI, mean summed ST-deviation was 21 ± 8 mm with only minimal ST-resolution after PCI. One patient in the IABP group reached the primary end point versus four patients in the control group (2% vs. 8%; p = 0.16). After primary PCI, resolution of ST-deviation was significantly more pronounced in the IABP group (73 ± 17%) compared to the control group (56 ± 26%; p < 0.01). CONCLUSIONS: In this pilot study, in patients with large STEMI and persistent ischemia after primary PCI, use of IABP showed a nonsignificant decrease in mortality, necessity for (additional) mechanical hemodynamic support or readmission for heart failure at 6 months, and resulted in more rapid ST-resolution.

Perforation of a Saphenous Vein Graft Anastomosed at a Y-Configuration to the Left Internal Mammary Artery.

Perforation of a saphenous vein graft (SVG) is a rare, yet dreadful complication during percutaneous coronary intervention (PCI). Perforation of a SVG arising at a Y-construction from the left internal mammary artery (LIMA) can be catastrophic since manipulations and material delivery through the single LIMA inflow can aggravate ischemia and accelerate hemodynamic collapse. Prior CABG and pericardial obliteration should not offer reassurance against tamponade, since coronary perforation in these patients may cause the development of loculated pericardial effusions, a complication associated with high mortality. Treating physicians must be alert for potential periprocedural pitfalls during PCI in post-CABG patients and these should be taken into consideration during interventional planning, procedure and follow-up.

Pressure gradient vs. flow relationships to characterize the physiology of a severely stenotic aortic valve before and after transcatheter valve implantation.

Aims: Echocardiography and tomographic imaging have documented dynamic changes in aortic stenosis (AS) geometry and severity during both the cardiac cycle and stress-induced increases in cardiac output. However, corresponding pressure gradient vs. flow relationships have not been described. Methods and results: We recruited 16 routine transcatheter aortic valve implantations (TAVI's) for graded dobutamine infusions both before and after implantation; 0.014″ pressure wires in the aorta and left ventricle (LV) continuously measured the transvalvular pressure gradient (ΔP) while a pulmonary artery catheter regularly assessed cardiac output by thermodilution. Before TAVI, ΔP did not display a consistent relationship with transvalvular flow (Q). Neither linear resistor (median R2 0.16) nor quadratic orifice (median R2 < 0.01) models at rest predicted stress observations; the severely stenotic valve behaved like a combination. The unitless ratio of aortic to left ventricular pressures during systolic ejection under stress conditions correlated best with post-TAVI flow improvement. After TAVI, a highly linear relationship (median R2 0.96) indicated a valid valve resistance. Conclusion: Pressure loss vs. flow curves offer a fundamental fluid dynamic synthesis for describing aortic valve pathophysiology. Severe AS does not consistently behave like an orifice (as suggested by Gorlin) or a resistor, whereas TAVI devices behave like a pure resistor. During peak dobutamine, the ratio of aortic to left ventricular pressures during systolic ejection provides a 'fractional flow reserve' of the aortic valve that closely approximates the complex, changing fluid dynamics. Because resting assessment cannot reliably predict stress haemodynamics, 'valvular fractional flow' warrants study to explain exertional symptoms in patients with only moderate AS at rest.

Safety and feasibility of selective intracoronary hypothermia in acute myocardial infarction.

AIMS: Hypothermia reduces reperfusion injury and infarct size in animal models of acute myocardial infarction if started before reperfusion. Human studies have not confirmed benefit, probably due to insufficient myocardial cooling and adverse systemic effects. This study sought to assess the safety and feasibility of a novel method for selective, sensor-monitored intracoronary hypothermia. METHODS AND RESULTS: Ten patients undergoing primary percutaneous coronary intervention (PPCI) were included. Saline at room temperature was administered distal to the culprit lesion through an inflated overthe- wire balloon (OTWB) in order to cool the endangered myocardium for 10 minutes (occlusion phase). Next, the OTWB was deflated and cooling continued with saline at 4°C for another 10 minutes (reperfusion phase). A sensor-tipped temperature wire in the distal coronary artery allowed titration of the infusion rate to achieve the desired coronary temperature (6°C below body temperature). Target coronary temperature was achieved within 27 seconds (median; IQR 21-46). Except for two patients with inferior wall infarction experiencing transient conduction disturbances, no side effects occurred. Systemic temperature remained unchanged. Finally, PPCI was performed as per routine. CONCLUSIONS: Selective hypothermia of the infarct area by intracoronary infusion of saline provides a novel method to reduce coronary temperature quickly and guarantee local myocardial hypothermia. In anterior wall myocardial infarctions, the protocol appeared safe, without serious haemodynamic or systemic side effects. In inferior wall myocardial infarctions, transient conduction abnormalities of short duration occurred. Potentially, selective intracoronary delivery of hypothermia could attenuate reperfusion injury caused by traditional PPCI.

Single bolus intravenous regadenoson injection versus central venous infusion of adenosine for maximum coronary hyperaemia in fractional flow reserve measurement.

AIMS: The aim of this study was to compare the hyperaemic effect of a single bolus regadenoson injection to a central venous adenosine infusion for inducing hyperaemia in the measurement of fractional flow reserve (FFR). METHODS AND RESULTS: One hundred patients scheduled for FFR measurement were enrolled. FFR was first measured by IV adenosine (140 µg/kg/min), thereafter by IV bolus regadenoson injection (400 µg), followed by another measurement by IV adenosine and bolus injection of regadenoson. The regadenoson injections were randomised to central or peripheral intravenous. Hyperaemic response and duration of steady state maximum hyperaemia were studied, central versus peripheral venous regadenoson injections were compared, and safety and reproducibility of repeated injections were investigated. Mean age was 66±8 years, 75% of the patients were male. The target stenosis was located in the LM, LAD, LCX, and RCA in 7%, 54%, 20% and 19%, respectively. There was no difference in FFR measured by adenosine or by regadenoson (ΔFFR=0.00±0.01, r=0.994, p<0.001). Duration of maximum hyperaemia after regadenoson was variable (10-600 s). No serious side effects of either drug were observed. CONCLUSIONS: Maximum coronary hyperaemia can be achieved easily, rapidly, and safely by one single intravenous bolus of regadenoson administered either centrally or peripherally. Repeated regadenoson injections are safe. The hyperaemic plateau is variable. Clinical Trial Registration: http://clinicaltrials.gov/ct2/ show/study/NCT01809743?term=NCT01809743&rank=1 (ClinicalTrials.gov Identifier: NCT01809743).

Trends in the occurrence of new conduction abnormalities after transcatheter aortic valve implantation.

OBJECTIVES: The aim of the study was to investigate trends over time in the occurrence of left bundle branch block (LBBB) and permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) with the Medtronic CoreValve System (MCS) and Edwards SAPIEN Valve (ESV). BACKGROUND: TAVI-induced conduction abnormalities (TAVI-CAs) such as LBBB and the need for PPI are frequent postoperative complication. New techniques, procedural refinements, and increased awareness are focused on the reduction of these abnormalities. METHODS: Electrocardiograms of 549 patients without preprocedural LBBB and/or pacemaker were assessed to determine the frequency and nature of TAVI-CAs. To study the effect of experience, patients were subdivided per center into tertiles based on the number of procedures. Univariate and multivariate logistic regression was used to study predictors of TAVI-induced LBBB (TAVI-LBBB) and PPI. RESULTS: TAVI-LBBB occurred in 185 patients (33.7%) and significantly decreased over time, from 42.6% to 27.3% (P=0.006). This effect was only significant after implantation of the MCS (59.6% vs. 46.5% vs. 31.1%, P=0.001, ESV: 22.6% vs. 13.1% vs. 24.8%, P=0.11). Between tertiles there was no difference in the frequency of PPI after TAVI (n=73, 13.1% vs. 14.8% vs. 12%, P=0.74). Multivariate analysis revealed that, independent from valve type, depth of implantation was the only significant predictor of TAVI-LBBB (OR [95% C.I.]: 1.16 [1.10-1.24], P<0.001). In case of PPI pre-existing RBBB (OR [95% C.I.]: 7.22 [3.28-15.88], P<0.001) was the only significant predictor. CONCLUSIONS: Over time the frequency of LBBB after TAVI decreased significantly, especially in patients undergoing TAVI with the MCS. Experience and the subsequent reduction in depth of implantation seem responsible for this reduction. Contrary to TAVI-LBBB, the incidence of PPI remained unchanged over time and was not affected by experience. Although experience has led to a decrease in new CAs after TAVI, elucidation of pathophysiologic mechanisms underlying these CAs and subsequent changes in patient stratification, valve design and the procedure are needed to further reduce this complication.

Left bundle-branch block induced by transcatheter aortic valve implantation increases risk of death.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a novel therapy for treatment of severe aortic stenosis. Although 30% to 50% of patients develop new left bundle-branch block (LBBB), its effect on clinical outcome is unclear. METHODS AND RESULTS: Data were collected in a multicenter registry encompassing TAVI patients from 2005 until 2010. The all-cause mortality rate at follow-up was compared between patients who did and did not develop new LBBB. Of 679 patients analyzed, 387 (57.0%) underwent TAVI with the Medtronic CoreValve System and 292 (43.0%) with the Edwards SAPIEN valve. A total of 233 patients (34.3%) developed new LBBB. Median follow-up was 449.5 (interquartile range, 174-834) days in patients with and 450 (interquartile range, 253-725) days in patients without LBBB (P=0.90). All-cause mortality was 37.8% (n=88) in patients with LBBB and 24.0% (n=107) in patients without LBBB (P=0.002). By multivariate regression analysis, independent predictors of all-cause mortality were TAVI-induced LBBB (hazard ratio [HR], 1.54; confidence interval [CI], 1.12-2.10), chronic obstructive lung disease (HR, 1.56; CI, 1.15-2.10), female sex (HR, 1.39; CI, 1.04-1.85), left ventricular ejection fraction ≤50% (HR, 1.38; CI, 1.02-1.86), and baseline creatinine (HR, 1.32; CI, 1.19-1.43). LBBB was more frequent after implantation of the Medtronic CoreValve System than after Edwards SAPIEN implantation (51.1% and 12.0%, respectively; P<0.001), but device type did not influence the mortality risk of TAVI-induced LBBB. CONCLUSIONS: All-cause mortality after TAVI is higher in patients who develop LBBB than in patients who do not. TAVI-induced LBBB is an independent predictor of mortality.