Cameron G. Densem

Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial.

Background— Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Methods and Results— Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P=0.01). Subjects who received remote IPC experienced less chest discomfort (P=0.0006) and ECG ST-segment deviation (P=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P=0.018). Conclusion— Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.

Standalone balloon aortic valvuloplasty: Indications and outcomes from the UK in the transcatheter valve era

We sought to characterize UK‐wide balloon aortic valvuloplasty (BAV) experience in the TAVI era.

Transcatheter aortic valve insertion: anaesthetic implications of emerging new technology

Transcatheter aortic valve insertion is a new development that potentially offers a number of advantages to patients and healthcare providers. These include the avoidance of sternotomy and cardiopulmonary bypass, and much faster discharge from hospital and return to functional status. The procedure itself however is quite complex, and presents significant demands in planning and implementation to the multidisciplinary team. Anaesthetic input is essential, and patient care in the perioperative period can be challenging. Early results have shown a significant mortality and morbidity rate, but the majority of procedures to date have been carried out in elderly patients with multiple comorbidities, making comparison with surgical aortic valve replacement inappropriate. Long-term outcomes are not yet known, but randomized controlled trials should allow this procedure and its application to be properly assessed.

Leukocyte Telomere Length Is Associated With High-Risk Plaques on Virtual Histology Intravascular Ultrasound and Increased Proinflammatory Activity

Objective— Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown. Methods and Results— One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01–1.53; P=0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02–1.39; P=0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1&bgr; and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10. Conclusion— Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity.

Remote ischaemic pre‐conditioning does not attenuate ischaemic left ventricular dysfunction in humans

Remote ischaemic pre‐conditioning (RIPC) reduces distant tissue ischaemia reperfusion injury. We tested the hypothesis that RIPC would protect the left ventricle (LV) from ischaemic dysfunction and stunning.

Primary coronary microvascular dysfunction and poor coronary collaterals predict post-percutaneous coronary intervention cardiac necrosis

BackgroundAn elevation in cardiac troponin-I (cTnI) after elective percutaneous coronary intervention (PCI) is because of cardiac necrosis and has prognostic implications. Primary microvascular dysfunction, evident before PCI, and paucity of coronary collaterals at baseline may influence cTnI. MethodsWe selected 22 patients awaiting elective PCI for a single-vessel, type-A coronary stenosis, with normal left ventricular function and a normal preprocedure cTnI. Intracoronary pressure and Doppler flow were measured during coronary balloon occlusion to derive microvascular resistance: Rp=[Pd(occl)–Pv]/APVoccl and collateral resistance: Rcoll=[Pa–Pd(occl)]/APVoccl, at each stage of PCI, where Pa is mean aortic pressure, Pv is central venous pressure, Pd(occl) is mean distal pressure, Rp is coronary microvascular resistance, Rcoll is coronary collateral resistance, and APVoccl is average peak velocity during coronary balloon occlusion. The resistance indices were compared with postprocedural cTnI levels measured at 24 h. ResultsThere was a relationship between baseline Rp before PCI and elevated plasma cTnI levels at 24 h. Mean (SEM) Rp (mmHg/cm/s) increased for each cTnI tertile: T1 (mean cTnI 0.04 ng/ml): 1.3 (0.3), T2 (mean cTnI 0.13 ng/ml): 3.1 (0.4), and T3 (mean cTnI 2.5 ng/ml): 4.6 (0.7) (P=0.002). Baseline Rcoll (mmHg/cm/s) was similarly related to cTnI result and mean values showed an increasing trend: T1: 11.1 (1.9), T2: 14.5 (2.3), and T3: 19.5 (3.4) (P=0.12). Serial coronary balloon occlusions did not significantly alter Rp (P=0.82) or recruit coronary collaterals (P=0.69). ConclusionPrimary coronary microvascular dysfunction and poor collaterals at baseline are associated with post-PCI necrosis.

Bacterial endocarditis associated with proteinase 3 anti-neutrophil cytoplasm antibody

Anti-neutrophil cytoplasm antibodies (ANCA) are useful diagnostic markers in a range of small vessel vasculitides. While non-specific ANCA have been reported in association with a variety of autoimmune, haematological and infectious conditions, the combination of a cytoplasmic staining pattern on indirect immunofluorescence (IIF) of human neutrophils, with antibodies specific for proteinase 3 (PR3) by enzyme-linked immunosorbent assay (ELISA), is reported to be 99% specific for Wegener’s granulomatosis versus disease controls [1]. This serological finding in association with other diseases that manifest vasculitic phenomena can therefore result in diagnostic uncertainty and erroneous treatment decisions. We report three cases of bacterial endocarditis in association with PR3-ANCA and discuss the implications for diagnosis and management.

81 Balloon Aortic Valvuloplasty in the Tavr ERA – Single Tertiary Centre Experience

Background The use of balloon aortic valvuloplasty (BAV) is increasing in the current transcatheter aortic valve replacement (TAVR) era. There are no clear guidelines regarding follow-up or predictors of functional and echocardiographic recovery following BAV, which can affect timing of subsequent intervention. We present our experience of BAV. Methods We performed retrospective analysis of patients who underwent BAV for severe aortic stenosis (AS) at our institution, between August 2008 and October 2013. We reviewed population characteristics, indications, periprocedural and follow-up transthoracic echocardiographic data (TTE). Results Between August 2008 and October 2013 86 BAV procedures were performed on 78 patients.A single BAV was performed in 72 patients, 6 had >1 procedure. Males 55.1% (n = 43), mean age 82.2 years, all had multiple co-morbidities. Indications for BAV included: i) symptoms palliation (n = 46), including discharge facilitation (n = 7), ii) facilitate non-cardiac surgery (n = 5), iii) assess symptomatic response (in multifactorial breathlessness) and potential bridge to destination therapy (n = 27); no data (n = 8). Patients were divided into 2 groups: group A, LV EF≥40% (n = 56) and group B, LV EF <40% (n = 25). AV area (AVA) improved significantly immediately after BAV (group A pre BAV 0.67cm2 ± 0.22 to 0.91cm2 ± 0.20, p < 0.05; group B 0.61cm2 ± 0.28 to 0.88cm2 ± 0.29, p < 0.05). Mortality over the period was 42.3% (n = 33), with deaths occurring in group A at median time of 9.5 months and in group B at 3.25 months following BAV. 13 patients underwent valve replacement, 4 surgical and 9 TAVR. Follow-up TTE was available in 33; group A, n = 22 (mean follow-up 4.2 months);group B, n = 11 (mean follow-up 2.7 months). Table 1 shows TTE data at baseline and follow-up. Abstract 81 Table 1 Group A (n = 22) Group B (n = 11) Baseline TTE (mean) Follow-up TTE (mean) Baseline TTE (mean) Follow-up TTE (mean) AVA (cm2) 0.70 ± 0.23 0.83 ± 0.29 0.64 ± 0.34 0.68 ± 0.35 pAVG (mmHg) 68.6 ± 22.4 64.2 ± 26.7 51.8 ± 21.2 55.3 ± 19.5 mAVG (mmHg) 36.9 ± 14.4 38.3 ± 18.2 28.2 ± 12.0 31.2 ± 11.4 LVEF≥40% <40% 22pts 20pts 0 pts 2pts LVEF (%) 23.1 ± 7.4 36.2 ± 11.9 AVA: aortic valve area, mAVG: mean AV gradient, pAVG: peak AVG Conclusions BAV was performed in a high risk elderly population for a number of indications. After BAV, an early improvement in all AS parameters was seen. It appears be a useful screening tool to help determine which patients will benefit from definitive therapy and used to facilitate discharge and palliation. Further data is needed to establish predictors of left ventricular recovery and optimal timing of subsequent interventions.

B VH-IVUS findings predict major adverse cardiovascular events. The Viva Study (virtual histology intravascular ultrasound in vulnerable atherosclerosis)

Background Identification of high-risk atherosclerotic plaques offers opportunities for risk stratification and targeted intensive treatment of patients with coronary artery disease. Virtual Histology intravascular ultrasound (VH-IVUS) has been validated in human atherectomy and post-mortem studies and can classify plaques into presumed high- and low-risk groups. However, VH-IVUS-defined plaques have not been shown to be associated with major adverse cardiovascular events (MACE), or biomarkers that confer increased cardiovascular risk, such as serum cytokines or shortened leukocyte telomere length (LTL). Methods 170 patients with stable angina or troponin-positive acute coronary syndrome (ACS), referred for percutaneous coronary intervention (PCI) were prospectively enrolled and underwent full 3-vessel VH-IVUS pre-PCI. Troponin-I (cTnI), IL-6, IL-18, hsCRP, neopterin, MCP-1 and sICAM-1 were measured pre-PCI and 24-h post-PCI. LTL was determined by qPCR. The combined primary endpoint (MACE) included unplanned revascularisation, myocardial infarction (MI) and death, with a secondary endpoint of post-PCI MI (MI 4a). Results 18 MACE occurred in 16 patients (median follow-up: 625 (463–990) days). 30 372 mm of VH-IVUS were analysed and 1106 plaques classified (Abstract B Figure 1) locally and via a core-lab. After multivariable regression:Abstract B Figure 1 Total number of non-calcified VH-IVUS-identified thin capped fibroatheromata (VHTCFA) was the only factor independently associated with MACE (HR=3.16, (95%CI=1.16 to 8.64), p=0.025). Total VHTCFA number (OR=1.26 (1.03 to 1.53) p=0.021) and total stent length (OR=1.04 (1.01 to 1.08), p=0.01) were the only factors independently associated with MI 4a. A novel 3-vessel vulnerability index (necrotic core: fibrous tissue ratio) and side branch loss were independently associated with stenting-related cTnI rise (standardised beta coefficient (sβ)=0.29, p=0.004 and sβ=0.23, p=0.019 respectively). Necrotic core area at the minimum luminal area frame was the only factor independently associated with ACS presentation (OR=1.59, p=0.030). Stented vessel VHTCFA number (OR=1.75 (1.22 to 2.51), p=0.002) was independently associated with the lower LTL tertile (DNA-based cardiovascular risk predictor). Stenting-related IL-6 rise was the only biomarker independently associated with MACE (HR=1.03 (1.01–1.05), p=0.007). Conclusion We present the first report of an association between VHTCFA and MACE. This provides novel evidence that VHTCFA definitions are important in their own right (rather than as analogues of histological TFCA definitions). We also present the first report of associations between VHTCFA and MI 4a as well as a novel vulnerability index that is association with stenting-related troponin rise. Finally, we report a novel association between VHTCFA and DNA-based cardiovascular risk prediction (LTL).

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies

Background We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Methods and Results Ten subjects with single‐vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low‐pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia‐induced diastolic dysfunction was seen 1 minute after RP (end‐diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P<0.001) and BO (end‐diastolic pressure [mm Hg]: 8.1±4.0 versus 8.7±4.0, P=0.03). Impairment of systolic and diastolic function after BO remained at 15‐minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P<0.01; end‐diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P<0.01). Persistent diastolic dysfunction was also evident in the RP group at 15‐minutes recovery (end‐diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P=0.03) and there was also sustained impairment of load‐independent indices of systolic function at 15 minutes after RP (end‐systolic elastance and ventriculo‐arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P<0.01). Conclusions RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve.