Contemporary tools and devices for coronary calcium modification

With the aging population, up to a third of patients referred for percutaneous coronary intervention (PCI) have moderate or severe calcified lesions assessed by coronary angiography. The presence of coronary calcium is associated with difficult device delivery, sub-optimal stent deployment, and prolonged procedures, with more complications. Furthermore, it is known that sub-optimal stent expansion is associated with poor clinical outcomes. In this manuscript we describe how to quantify the severity of coronary calcium, review the armamentarium of contemporary devices available for calcium modification, and provide a systematic approach to device selection, assessment of successful calcium modification, and stent optimization

Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction

<b>Background:</b> The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.<p></p> <b>Methods and Results:</b> The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.<p></p> <b>Conclusion:</b> Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.<p></p&gt

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success

The Impact of Calcium on Chronic Total Occlusion Management.

Coronary artery calcification is prevalent in chronic total occlusions (CTO), particularly in those of longer duration and post-coronary artery bypass. The presence of calcium predicts lower procedural success rates and a higher risk of complications of CTO percutaneous coronary intervention. Adjunctive imaging, including pre-procedural computed tomography and intracoronary imaging, are useful to understand the distribution and morphology of the calcium. Specialised guidewires and microcatheters, as well as penetration, subintimal entry and luminal re-entry techniques, are required to cross calcific CTOs. The use of both atherectomy devices and balloon-based calcium modification tools has been reported during CTO percutaneous coronary intervention, although they are limited by concerns regarding safety and efficacy in the subintimal space

Comparison of Characteristics and Complications in Men Versus Women Undergoing Chronic Total Occlusion Percutaneous Intervention

Gender differences exist in clinical outcomes after routine percutaneous coronary intervention (PCI), but studies reporting such outcomes after chronic total occlusion (CTO) PCI are limited. We assessed the characteristics and outcomes of female patients undergoing CTO PCI. We retrospectively analyzed a dedicated national (United Kingdom) prospective CTO database from 2011 to 2015 for outcomes and characteristics of female patients undergoing CTO PCI (unmatched and propensity matched). Female patients constituted 20.5% (n = 260 of 1,271) of the unmatched cohort and 33.3% (n = 233 of 699) of the matched cohort and were more likely to be older (women aged >70 years, 48% in the unmatched and 45% in the matched cohort). An increased inhospital complication rate was observed in female patients (unmatched: 10% women vs 4.45% men, p = 0.0012, and matched 9.87% women vs 3.86% men, p = 0.0032). Coronary perforation, bleeding, and contrast-induced nephropathy were more frequently observed in female patients. Femoral access site with >6 French sheath was associated with an increased risk of bleeding. Presence of calcification in the CTO artery was associated with coronary perforation (grade III) in female patients in the matched cohort (p = 0.007). Female patients undergoing CTO PCI were older and experienced increased of inhospital complications. Increased awareness of these complications could influence the selection of access site and sheath size, the need for prehydration, judicious choice of balloon size, collateral selection, and wire placement in female patients undergoing CTO PCI

Discordance between resting and hyperemic indices of coronary stenosis severity: the VERIFY 2 study (a comparative study of resting coronary pressure gradient, instantaneous wave-free ratio and fractional flow reserve in an unselected population referred for invasive angiography)

Background—Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR). We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods and Results—This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (P=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (P=0.55). Conclusions—Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02377310

Risk assessment for the spread of Serratia marcescens within dental-unit waterline systems using Vermamoeba vermiformis

Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpron™ this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpron™ indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1x108 colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for eight weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (p = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium

The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease

Background: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent mechanism. Methods: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled, and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses (10−6 , 10−5 , 10−4 mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography. The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235). Results: 75 patients were enrolled. Following angiography, 60 patients (mean ± SD age 57.5 ± 8.5 years; 80% male) were eligible and completed the protocol (n = 30 RIPC, n = 30 sham). The mean percentage change in coronary luminal diameter was −13.3 ± 22.3% and −2.0 ± 17.2% in the sham and RIPC groups respectively (difference 11.32%, 95%CI: 1.2– 21.4, p = 0.032). This remained significant when age and sex were included as covariates (difference 11.01%, 95%CI: 1.01– 21.0, p = 0.035). There were no between-group differences in endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function. Conclusions: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIP

Prognostic significance of infarct core pathology in ST-elevation myocardial infarction survivors revealed by non-contrast T1 mapping cardiac magnetic resonance

Background: Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute ST-elevation myocardial infarction (STEMI) patients is unknown. We aimed to assess the clinical significance of infarct core native T1. Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The infarct territory and microvascular obstruction (MVO) were depicted with late gadolinium enhancement CMR. Adverse remodeling was defined as an increase in LV end-diastolic volume (LVEDV) ≥ 20% at 6 months. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up. Results: 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps. Infarct size was 18 ±14% of LV mass. One hundred and forty five (50%) of 288 patients had late MVO, whereas 160 (56%) patients had infarct core pathology revealed by native T1. Native T1 within the infarct core (996.9±57.3; p&#60;0.01) was higher than in the remote zone (961±25 ms; p&#60;0.01) but lower than in the area-at-risk (1097 ±52 ms). In multivariable linear regression, native T1 in the infarct core was negatively associated with age, initial systolic blood pressure, TIMI coronary flow grade at initial angiography, Killip class at presentation and neutrophil count (all p&#60;0.05), independent of LVEF, LVEDV or infarct size. At 6 months, LVEDV increased by 5 (25) ml (n=262 patients with evaluable data). Adverse remodeling occurred in 30 (12%) patients and 23 (76.7%) of these patients MVO at baseline. T1 in the infarct core was a multivariable predictor of adverse remodeling (-0.01 (-0.02, -0.00); p=0.048). 288 (100%) patients were followed-up for a median of 845 days. Thirty (10.4%) patients died or experienced a heart failure event and 13 (4.5%) of these patients experienced the event post-discharge. Infarct core native T1 predicted all-cause death or heart failure post-discharge (hazard ratio 0.969, 95% CI 0.953, 0.985; p&#60;0.001) including after adjustment for LVEF (p&#60;0.001) and LVEDV at baseline (p&#60;0.001), and was comparable with MVO

Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction

The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P&lt;0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P&lt;0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P&lt;0.001) were multivariable associates of the change in remote zone ECV at 6 months (ΔECV). ΔECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10–2.76); P=0.036). ΔECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling