Arterial access site utilization in cardiogenic shock in the United Kingdom: is radial access feasible?

in American heart journal (2014), 167(6), 900-81

BACKGROUND: Cardiogenic shock (CS) remains the leading cause of mortality in patients hospitalized with acute myocardial infarction (AMI). The transradial access site (TRA) has become increasingly adopted ... [more ▼]

BACKGROUND: Cardiogenic shock (CS) remains the leading cause of mortality in patients hospitalized with acute myocardial infarction (AMI). The transradial access site (TRA) has become increasingly adopted as a default access site for percutaneous coronary intervention (PCI); however, even in experienced centers that favor the radial artery as the primary access site during PCI, patients presenting in CS are often treated via the transfemoral access site (TFA); and commentators have suggested that CS remains the final frontier that has given even experienced radial operators pause. We studied the use of TRA in patients presenting in CS in a nonselected high-risk cohort from the British Cardiovascular Intervention database over a 7-year period (2006-2012). METHODS: Mortality (30-day) and major adverse cardiac and cerebrovascular events (a composite of in-hospital mortality, in-hospital myocardial reinfarction, target vessel revascularization, and cerebrovascular events) were studied based on TFA and TRA utilization in CS patients. The influence of access site selection was studied in 7,231 CS patients; TFA was used in 5,354 and TRA in 1,877 patients. RESULTS: Transradial access site was independently associated with a lower 30-day mortality (hazard ratio [HR] 0.56, 95% CI 0.46-0.69, P = 0 < .001), in-hospital major adverse cardiac and cerebrovascular events (HR 0.64, 95% CI 0.53-0.76, P < .0001) and major bleeding (HR 0.37, 95% CI 0.18-0.73, P = .004). CONCLUSIONS: Although the majority of PCI cases performed in patients with cardiogenic shock in the United Kingdom are performed through the TFA, the radial artery represents an alternative viable access site in this high-risk cohort of patients in experienced centers. [less ▲]

Serum sphingolipids level as a novel potential marker for early detection of human myocardial ischaemic injury.

in Frontiers in physiology (2013), 4

Background: Ventricular tachyarrhythmias are the most common and often the first manifestation of coronary heart disease and lead to sudden cardiac death (SCD). Early detection/identification of acute ... [more ▼]

Background: Ventricular tachyarrhythmias are the most common and often the first manifestation of coronary heart disease and lead to sudden cardiac death (SCD). Early detection/identification of acute myocardial ischaemic injury at risk for malignant ventricular arrhythmias in patients remains an unmet medical need. In the present study, we examined the sphingolipids level after transient cardiac ischaemia following temporary coronary artery occlusion during percutaneous coronary intervention (PCI) in patients and determined the role of sphingolipids level as a novel marker for early detection of human myocardial ischaemic injury. Methods and Results: Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) from 31 patients aged 40-73 years-old at 1, 5 min, and 12 h, following elective PCI. Plasma sphingolipids levels were assessed by HPLC. At 1 min coronary sinus levels of sphingosine 1-phosphate (S1P), sphingosine (SPH), and sphinganine (SA) were increased by 314, 115, and 614%, respectively (n = 7), while peripheral blood levels increased by 79, 68, and 272% (n = 24). By 5 min, coronary sinus S1P and SPH levels increased further (720%, 117%), as did peripheral levels of S1P alone (792%). Where troponin T was detectable at 12 h (10 of 31), a strong correlation was found with peak S1P (R (2) = 0.818; P < 0.0001). Conclusion: For the first time, we demonstrate the behavior of plasma sphingolipids following transient cardiac ischaemia in humans. The observation supports the important role of sphingolipids level as a potential novel marker of transient or prolonged myocardial ischaemia. [less ▲]

Atrial fibrillation in heart failure: The sword of Damocles revisited.

in World Journal of Cardiology (2013), 5(7), 215-27

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and ... [more ▼]

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and affects patients with both reduced as well as preserved LV systolic function. There has been a general move in clinical practice from a rhythm control to a rate control strategy in HF patients with AF, although recent data suggests that rhythm control strategies may provide better outcomes in selected subgroups of HF patients. Furthermore, various therapeutic modalities including pace and ablate strategies with cardiac resynchronisation or radiofrequency ablation have become increasingly adopted, although their role in the management of AF in patients with HF remains uncertain. This article presents an overview of the multidimensional impact of AF in patients with HF. Relevant literature is highlighted and the effect of various therapeutic modalities on prognosis is discussed. Finally, while novel anticoagulants usher in a new era in thromboprophylaxis, research continues in a variety of new pathways including selective atrial anti-arrhythmic agents and genomic polymorphisms in AF with HF. [less ▲]

Use of the Sideguard (Cappella) stent in bifurcation lesions: a real-world experience.

in EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology (2012), 7(10), 1170-80

AIMS: The Sideguard(R) stent (Cappella Medical Devices Ltd, Galway, Ireland), is a novel nitinol self-expanding dedicated bifurcation stent that flares proximally at the ostium of the side branch (SB ... [more ▼]

AIMS: The Sideguard(R) stent (Cappella Medical Devices Ltd, Galway, Ireland), is a novel nitinol self-expanding dedicated bifurcation stent that flares proximally at the ostium of the side branch (SB) into a trumpet shape thereby achieving full ostial coverage. The aim of this study is to report the utility and limitations of this stent in patients undergoing treatment to bifurcation coronary lesions in a real-world setting. METHODS AND RESULTS: We prospectively identified 20 successive patients admitted over a 6-month period in whom there was significant SB disease and who were suitable for a bifurcation procedure. The Sideguard(R) stent was successfully used in all 20 cases including several that would have been technically difficult using conventional bifurcation techniques. We highlight use of this system using five illustrative cases that illustrate its utility and limitations in the treatment of bifurcation lesions. CONCLUSIONS: The Sideguard(R) stent can be used to treat complex bifurcation lesions in a straight forward manner and is not subject to the limitations associated with conventional bifurcation PCI techniques including jailing of the SB ostium and inability to fully cover/scaffold the ostium of the SB. [less ▲]

Automated workflows for accurate mass-based putative metabolite identification in LC/MS-derived metabolomic datasets.

in Bioinformatics (2011), 27(8), 1108-12

MOTIVATION: The study of metabolites (metabolomics) is increasingly being applied to investigate microbial, plant, environmental and mammalian systems. One of the limiting factors is that of chemically ... [more ▼]

MOTIVATION: The study of metabolites (metabolomics) is increasingly being applied to investigate microbial, plant, environmental and mammalian systems. One of the limiting factors is that of chemically identifying metabolites from mass spectrometric signals present in complex datasets. RESULTS: Three workflows have been developed to allow for the rapid, automated and high-throughput annotation and putative metabolite identification of electrospray LC-MS-derived metabolomic datasets. The collection of workflows are defined as PUTMEDID_LCMS and perform feature annotation, matching of accurate m/z to the accurate mass of neutral molecules and associated molecular formula and matching of the molecular formulae to a reference file of metabolites. The software is independent of the instrument and data pre-processing applied. The number of false positives is reduced by eliminating the inaccurate matching of many artifact, isotope, multiply charged and complex adduct peaks through complex interrogation of experimental data. AVAILABILITY: The workflows, standard operating procedure and further information are publicly available at http://www.mcisb.org/resources/putmedid.html. CONTACT: warwick.dunn@manchester.ac.uk. [less ▲]

Late outcomes of drug eluting and bare metal stents in saphenous vein graft percutaneous coronary intervention.

in EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology (2011), 6(8), 985-91

AIMS: PCI with drug eluting stents (DES) has been shown to reduce restenosis and major adverse cardiac event (MACE) rates compared to bare metal stents (BMS) in native coronary vessels, although outcomes ... [more ▼]

AIMS: PCI with drug eluting stents (DES) has been shown to reduce restenosis and major adverse cardiac event (MACE) rates compared to bare metal stents (BMS) in native coronary vessels, although outcomes in saphenous vein graft (SVG) lesions are less clear. We retrospectively studied 388 consecutive patients admitted to our centre for SVG PCI to assess mortality and MACE outcomes (defined as composite endpoint of all-death, stroke, myocardial infarction, stent thrombosis and target lesion (TLR)/vessel (TVR) revascularisation) associated with BMS and DES use. METHODS AND RESULTS: Two hundred and nineteen (219) patients had BMS and 169 had DES (total 388 patients). Mean follow up was 41.9+/-23.5 months. No significant differences were observed in mortality (14.2% vs. 11.8%) or MACE (37.6% vs. 35.8%) between the BMS and DES groups at four years follow-up or at other intervening time points studied. Similarly, no differences in TVR/TLR rates were observed over a similar time period (19.8% vs. 21.6%). CONCLUSIONS: We have observed that DES and BMS use in SVG PCI have comparable mortality and MACE rates, and that in contrast to PCI in native coronary arteries, DES do not reduce revascularisation rates in our study cohort. [less ▲]

Resting Pd/Pa measured with intracoronary pressure wire strongly predicts fractional flow reserve.

in The Journal of invasive cardiology (2010), 22(6), 260-5

OBJECTIVE: To investigate the relationship between resting distal coronary pressure to aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) obtained during maximal hyperemia. BACKGROUND: FFR is ... [more ▼]

OBJECTIVE: To investigate the relationship between resting distal coronary pressure to aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) obtained during maximal hyperemia. BACKGROUND: FFR is an invasive index of the functional severity of a coronary artery stenosis determined from coronary pressure measurements. It is generally believed that there is little correlation between resting Pd/Pa and FFR obtained during maximal hyperemia. We have therefore studied this relationship in a large cohort of patients who had undergone pressure- wire assessments. METHODS: 528 consecutive pressure-wire studies performed in 483 patients over a 2-year period were retrospectively analyzed. RESULTS: A linear correlation between resting Pd/Pa and FFR post-pharmacological hyperemia was observed (rho = 0.74; p < 0.0001). When a FFR of < or = 0.75 (or < or = 0.80 as per FAME) was defined as positive, a resting Pd/Pa of < or = 0.85 (< or = 0.87) had a positive predictive value (PPV) of 95% (94.6%), while a resting Pd/Pa of > or = 0.93 (> or = 0.96) had a negative predictive value (NPV) of 95.7% (93%). CONCLUSIONS: We demonstrate a strong correlation between resting Pd/Pa and FFR. Resting values of Pd/Pa can be used to predict a positive FFR result with relatively high PPV and NPV. This may potentially obviate the need for adenosine infusion in a proportion of pressure-wire studies. [less ▲]

A meta-analysis of glucose-insulin-potassium therapy for treatment of acute myocardial infarction.

in Experimental and Clinical Cardiology (2010), 15(2), 20-4

BACKGROUND: Glucose-insulin-potassium (GIK) therapy has been proposed to provide metabolic support to ischemic myocardium. A meta-analysis that included 1932 patients performed 10 years previously ... [more ▼]

BACKGROUND: Glucose-insulin-potassium (GIK) therapy has been proposed to provide metabolic support to ischemic myocardium. A meta-analysis that included 1932 patients performed 10 years previously demonstrated that GIK therapy may have an important role in reducing mortality after acute myocardial infarction (AMI). Since then, many larger randomized trials investigating the role of GIK in the setting of AMI have been published; hence, the present study repeats the previous meta-analysis performed by the current authors to include these trials. METHOD AND RESULTS: A systematic MEDLINE search for all randomized, placebo-controlled studies of GIK therapy in the setting of AMI was conducted and a meta-analysis of the mortality data was performed. A total of 16 randomized trials from 1966 to 2008 were identified, with 28,374 patients included in the current meta-analysis. There was a total of 1367 deaths (9.6%) in the GIK group, with 1351 deaths (9.6%) in the control group. Meta-analysis did not reveal any benefit from GIK treatment (OR 1.0; 95% CI 0.9 to 1.1; P=0.9). Subgroup analysis of patients given high-dose GIK and in patients in whom reperfusion was not obtained did not demonstrate a benefit from GIK therapy. CONCLUSION: A meta-analysis of 16 randomized trials that spanned 40 years and involved more than 28,000 patients did not reveal any mortality benefit for ST segment elevation AMI using GIK therapy when data from the modern thrombolysis/primary percutaneous coronary intervention era were included. [less ▲]

Atrial fibrillation is under-recognized in chronic heart failure: insights from a heart failure cohort treated with cardiac resynchronization therapy.

in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (2009), 11(10), 1295-300

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic heart failure (CHF). Under-detection of asymptomatic paroxysmal AF (PAF) underestimates the true burden of ... [more ▼]

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic heart failure (CHF). Under-detection of asymptomatic paroxysmal AF (PAF) underestimates the true burden of AF in patients with CHF. We retrospectively studied the prevalence of asymptomatic PAF in 162 CHF patients through analysis of cardiac resynchronization therapy (CRT) device downloads to determine whether these episodes are associated with adverse outcomes. METHODS AND RESULTS: An episode of AF was defined by mode switching on CRT devices with an atrial rate >200 for at least 30 s. Of the 101 patients thought to be persistently in sinus rhythm (SR), 27% were found to have significant paroxysms of AF, with the cumulative percentage of time in the 'mode-switch mode' (i.e. the AF burden) of 1.6 +/- 0.9%. Mortality was 19.2% in patients with newly identified PAF with hospitalization and thrombo-embolism rates of 42.3 and 2.1%, respectively, compared with mortality of 10.4% with hospitalization and thrombo-embolism rates of 41.8 and 1.9%, respectively, in patients persistently in SR (P= NS). CONCLUSION: Analysis of data from CRT devices in a population of CHF patients with severe left ventricular dysfunction shows that a significant proportion of those perceived to be persistently in SR have undiagnosed paroxysms of AF but with relatively low burden. These episodes appear to be associated with a trend towards increased mortality but no effects on hospitalization or thrombo-embolism rates. [less ▲]

Targeting the sarcolemmal calcium pump: a potential novel strategy for the treatment of cardiovascular disease.

in Cardiovascular and Hematological Agents in Medicinal Chemistry (2007), 5(4), 300-4

Intracellular calcium dynamics play a very important role in mediating contraction and signalling in cardiomyocytes and vascular smooth muscle cells. A number of calcium transporters have been identified ... [more ▼]

Intracellular calcium dynamics play a very important role in mediating contraction and signalling in cardiomyocytes and vascular smooth muscle cells. A number of calcium transporters have been identified that orchestrate a complex process of excitation-contraction coupling and molecular signalling. Despite the variability of the calcium transporters expressed in cardiomyocytes, most calcium channel blockers used therapeutically target the L-type calcium channel and exhibit antihypertensive and/or vasodilating activities. Recently, another calcium pump which is located in the sarcolemma has been shown to mediate cardiac contractility and vascular tone. Interestingly, this sarcolemmal calcium pump (also known as Plasma Membrane Calcium/calmodulin dependent ATPase or PMCA) exerts its function not by altering global calcium concentration, but by mediating signal transduction pathways. This review will discuss recent advances that support the key roles of PMCA as signalling molecule and the potential to target this calcium pump as a novel approach for the treatment of cardiovascular disease. [less ▲]