Safety of therapeutic hypothermia in post VF/VT cardiac arrest patients.

Therapeutic hypothermia (TH) is a process of cooling a patient post ventricular tachycardia/ventricular fibrillation (VT/VF) cardiac arrest to 32-34 degrees C for 24 hours. This improves neurological outcome and is part of current guidelines. Hypothermia prolongs QT interval, which can precipitate torsades de pointes (TdP). We performed a retrospective review of all patients who received TH in our hospital over a period of 2 years to assess the effect of TH on the corrected OT interval (QTc) and any possible pro-arrhythmia. A total of 13 patients received TH. QTc prolonged in all patients with an average of 80.3 + 57.2 ms., and up to 109.8 + 80.4 ms in patients who received Amiodarone concurrently. No TdP was seen in any patient. We conclude that TH is safe, though careful monitoring of the OTc interval is advisable especially with concurrent use of QT prolonging drugs.

Permanent pacemaker insertion after CoreValve transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative).

BACKGROUND: Permanent pacemaker (PPM) requirement is a recognized complication of transcatheter aortic valve implantation. We assessed the UK incidence of permanent pacing within 30 days of CoreValve implantation and formulated an anatomic and electrophysiological model. METHODS AND RESULTS: Data from 270 patients at 10 centers in the United Kingdom were examined. Twenty-five patients (8%) had preexisting PPMs; 2 patients had incomplete data. The remaining 243 were 81.3±6.7 years of age; 50.6% were male. QRS duration increased from 105±23 to 135±29 milliseconds (P<0.01). Left bundle-branch block incidence was 13% at baseline and 61% after the procedure (P<0.001). Eighty-one patients (33.3%) required a PPM within 30 days. Rates of pacing according to preexisting ECG abnormalities were as follows: right bundle-branch block, 65.2%; left bundle-branch block, 43.75%; normal QRS, 27.6%. Among patients who required PPM implantation, the median time to insertion was 4.0 days (interquartile range, 2.0 to 7.75 days). Multivariable analysis revealed that periprocedural atrioventricular block (odds ratio, 6.29; 95% confidence interval, 3.55 to 11.15), balloon predilatation (odds ratio, 2.68; 95% confidence interval, 2.00 to 3.47), use of the larger (29 mm) CoreValve prosthesis (odds ratio, 2.50; 95% confidence interval, 1.22 to 5.11), interventricular septum diameter (odds ratio, 1.18; 95% confidence interval, 1.10 to 3.06), and prolonged QRS duration (odds ratio, 3.45; 95% confidence interval, 1.61 to 7.40) were independently associated with the need for PPM. CONCLUSION: One third of patients undergoing a CoreValve transcatheter aortic valve implantation procedure require a PPM within 30 days. Periprocedural atrioventricular block, balloon predilatation, use of the larger CoreValve prosthesis, increased interventricular septum diameter and prolonged QRS duration were associated with the need for PPM.

A survey of patients' attitudes to clinical research.

Every year hundreds of patients voluntarily participate in clinical trials across Ireland. However, little research has been done as to how patients find the experience. This survey was conducted in an attempt to ascertain clinical trial participants' views on their experience of participating in a clinical trial and to see and how clinical trial participation can be improved. One hundred and sixty-six clinical trial participants who had recently completed a global phase IV cardiovascular endpoint clinical trial were sent a 3-page questionnaire. Ninety-one (91%) respondents found the experience of participating in a clinical trial a good one with 85 (84.16%) respondents saying they would recommend participating in a clinical trial to a friend or relative and eighty-five (87.63%) respondents feeling they received better healthcare because they had participated in a clinical trial.

Infective endocarditis: a retrospective cohort study.

BACKGROUND: Infective endocarditis (IE) is a potentially life-threatening infection of the heart's endocardial surface. Despite advances in the diagnosis and management of IE, morbidity and mortality remain high. AIM: To characterize the demographics, bacteriology and outcomes of IE cases presenting to an Irish tertiary referral centre. DESIGN: Retrospective cohort study. METHODS: Patients were identified using Hospital Inpatient Enquiry and Clinical Microbiology inpatient consult data, from January 2005 to January 2014. Patients were diagnosed with IE using Modified Duke Criteria. Standard Bayesian statistics were employed for analysis and cases were compared to contemporary international registries. RESULTS: Two hundred and two patients were diagnosed with IE during this period. Mean age 54 years. Of these, 136 (67%) were native valve endocarditis (NVE), 50 (25%) were prosthetic valve endocarditis (PVE) and 22 (11%) were cardiovascular implantable electronic device-associated endocarditis. Culprit organism was identified in 176 (87.1%) cases and Staphylococcal species were the most common (57.5%). Fifty-nine per cent of NVE required surgery compared to 66% of PVE. Mean mortality rate was 17.3%, with NVE being the lowest (12.5%) and PVE the highest (32%). Increasing age was also associated with increased mortality. Fifty-three (26.2%) patients had embolic complications. CONCLUSIONS: This Irish cohort exhibited first-world demographic patterns comparable to those published in contemporary international literature. PVE required surgery more often and was associated with higher rates of mortality than NVE. Embolic complications were relatively common and represent important sequelae, especially in the intravenous drug user population. It is also pertinent to aggressively treat older cohorts as they were associated with increased mortality.

Multivessel coronary thrombosis resulting from heparin induced thrombocytopenia.

Thrombosis associated with a drop in the platelet count may occur in 33-50% of the patients who develop heparin-induced thrombocytopenia (HIT) during treatment with unfractionated heparin. We report the case of a 63-year-old man who was treated with unfractionated heparin following a non-ST segment elevation myocardial infarction (NSTEMI). He developed an acute ST segment elevation infarction (STEMI) on day 3 with an associated severe thrombocytopenia. He was successfully treated with percutaneous intervention and aspiration of coronary thrombus from the right coronary artery and the left circulflex artery, followed by an infusion a direct thrombin inhibitor lepirudin/bivalirudin. He made an excellent recovery.

Early and mid-term outcomes after transcatheter aortic valve implantation (TAVI) in Ireland.

BACKGROUND: TAVI is a percutaneous approach to aortic valve replacement in high surgical risk patients deemed inoperable. AIM: To evaluate the early and mid-term outcomes for an Irish TAVI cohort over a six-year period at St James's Hospital and Blackrock Clinic, Dublin, Ireland. RESULTS: In total 147 patients, 56% male with an average age of 82 underwent TAVI between December 2008 and December 2014. Thirty day, one year and two year survival was 90.5%, 83% and 71% respectively. Major vascular complications and renal failure were the biggest predictors of mortality at 30 days (p = 0.02). We observed a pacing rate of 13.5%, the majority in patients who had Medtronic Corevalve implants (p < 0.05). With increasing procedural experience there was a reduction in length of stay from 10 days to 7.5 days. CONCLUSION: This review, the first of its kind in Ireland showed favorable rates of 30 day and one year and two year survival post TAVI with procedural success and complication rates similar to international registry data.

Bypass surgery versus stenting for the treatment of multivessel disease in patients with unstable angina compared with stable angina.

BACKGROUND: Earlier reports have shown that the outcome of balloon angioplasty or bypass surgery in unstable angina is less favorable than in stable angina. Recent improvements in percutaneous treatment (stent implantation) and bypass surgery (arterial grafts) warrant reevaluation of the relative merits of either technique in treatment of unstable angina. Methods and Results- Seven hundred fifty-five patients with stable angina were randomly assigned to coronary stenting (374) or bypass surgery (381), and 450 patients with unstable angina were randomly assigned to coronary stenting (226) or bypass surgery (224). All patients had multivessel disease considered to be equally treatable by either technique. Freedom from major adverse events, including death, myocardial infarction, and cerebrovascular events, at 1 year was not different in unstable patients (91.2% versus 88.9%) and stable patients (90.4% versus 92.6%) treated, respectively, with coronary stenting or bypass surgery. Freedom from repeat revascularization at 1 year was similar in unstable and stable angina treated with stenting (79.2% versus 78.9%) or bypass surgery (96.3% versus 96%) but was significantly higher in both unstable and stable patients treated with stenting (16.8% versus 16.9%) compared with bypass surgery (3.6% versus 3.5%). Neither the difference in costs between stented or bypassed stable or unstable angina ($2594 versus $3627) nor the cost-effectiveness was significantly different at 1 year. CONCLUSIONS: There was no difference in rates of death, myocardial infarction, and cerebrovascular event at 1 year in patients with unstable angina and multivessel disease treated with either stented angioplasty or bypass surgery compared with patients with stable angina. The rate of repeat revascularization of both unstable and stable angina was significantly higher in patients with stents.

Evidence of prolonged inflammation in unstable angina and non-Q wave myocardial infarction.

OBJECTIVES: This study was designed to document the inflammatory response up to one year after acute presentation with unstable angina (UA) and non-Q wave infarction (NQMI) as reflected by the expression of soluble cell adhesion molecules (CAMs). BACKGROUND: Coronary plaque inflammation is a key component in the pathogenesis of acute coronary syndromes. Cell adhesion molecules are critical mediators of the inflammatory process. Soluble forms of these molecules are detectable in serum and are elevated acutely in patients with UA and NQMI. METHODS: Patients presenting with UA and NQMI had serum samples taken at presentation and then after three, six and 12 months. A control group of similar age and gender distribution was used for comparison. Levels of soluble inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-selectin and platelet-selectin were measured using an ELISA technique. RESULTS: We studied 91 patients (M/F = 73/18, mean age 62 +/- 11 years, 56 UA and 35 NQMI) and 24 controls (M/F = 18/6, mean age 56 +/- 12 years). Levels of all four soluble CAMs were significantly elevated in both UA and NQMI patients at presentation, three and six months in comparison with controls. Levels in UA and NQMI groups fell between six and 12 months after initial presentation. CONCLUSIONS: The results suggest that the inflammatory stimulus triggering expression of CAMs is sustained for up to six months after presentation with either UA or NQMI and then returns toward control values over the following six months.

A dose-ranging, placebo-controlled, double-blind trial of nisoldipine in effort angina: duration and extent of antianginal effects.

Maximal treadmill exercise testing at 1, 3 and 8 hours was used to assess the onset, duration and antianginal efficacy of the dihydropyridine slow channel calcium-blocking agent, nisoldipine, in an oral dose range of 5, 10 and 20 mg. A double-blind, randomized, placebo-controlled design was used involving 12 patients with stable effort angina. Exercise tolerance was significantly increased 3 hours after each dose, when the maximal beneficial effect occurred. The improvement was observed as early as 1 hour after the 10 and 20 mg dose, and persisted for 8 hours after the 20 mg dose. At 3 hours, the onset of an exercise-induced ST segment depression of 0.1 mV or greater was increased by 62 (p less than 0.05), 75 (p less than 0.01) and 117 seconds (p less than 0.01) with the 5, 10 and 20 mg dose of nisoldipine, respectively, compared with placebo. Similarly, time to onset of angina was significantly increased. The sum of exercise-induced ST segment depression at peak exercise was significantly decreased (p less than 0.05) from 8.7 +/- 2.3 to 6.7 +/- 1.8 and 6.4 +/- 2.0 mm, respectively, after the 10 and 20 mg dose of nisoldipine. The rate-pressure product was significantly greater with nisoldipine than with placebo at the onset of ischemia and at peak exercise (22.8 +/- 1.1 versus 20 +/- 1.4 X 10(3) U for the 20 mg dose; p less than 0.01). Thus, nisoldipine is an effective antianginal agent with a rapid onset of action that improves exercise tolerance, increases angina threshold and persists for at least 8 hours after oral dosing.

Serial exercise testing in patients with effort angina: variable tolerance, fixed threshold.

To investigate the frequency and mechanism of variable threshold angina, seven treadmill exercise tests were performed in each of 28 patients with stable effort angina and exercise-induced ST segment depression. Each patient had tests at 8 AM on 4 days within a 2 week period and on 1 of these days had three additional tests at 9 AM, 11 AM and 4 PM. Time to 1 mm ST depression increased from 277 +/- 172 seconds on day 1 to 319 +/- 186 seconds on day 2, 352 +/- 213 seconds on day 3 and 356 +/- 207 seconds on day 4 (p less than 0.05). Rate-pressure product at 1 mm ST depression remained constant. Similarly, time to 1 mm ST depression increased from 333 +/- 197 seconds at 8 AM to 371 +/- 201 seconds at 9 AM and to 401 +/- 207 seconds at 11 AM and decreased to 371 +/- 189 seconds at 4 PM (p less than 0.01). Again, rate-pressure product at 1 mm ST depression remained constant. The standard deviation for time to 1 mm ST depression, calculated as a percent of the mean for each patient's seven tests and then averaged for the entire group, was 22 +/- 11%. The standard deviation for rate-pressure product at 1 mm ST depression, calculated in the same way, was significantly less at 8.4 +/- 2.8% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement.

OBJECTIVES: We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery. BACKGROUND: Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions. METHODS: Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (4 normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls. RESULTS: The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005). CONCLUSIONS: Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively.

Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes.

OBJECTIVES: The study was done to determine the role of partial agonist activity in the lack of effectiveness of the oral GPIIb/IIIa antagonist orbofiban. BACKGROUND: Orbofiban, an oral GPIIb/IIIa antagonist, was found to increase the mortality of patients with acute coronary syndromes (ACS) in the OPUS-TIMI-16 trial, despite the fact that it is a very potent anti-platelet agent and that IV agents have proven very effective. METHODS: Patients (n = 520) with ACS were randomized to orbofiban 30 mg, 40 mg or 50 mg twice daily or 50 mg once daily or placebo. Platelet activity was assessed in 175 patients by examining GPIIb/IIIa receptor conformation, expression of CD63 antigen, and platelet aggregation. RESULTS: Plasma concentrations of orbofiban at the highest dose (74 +/- 6 ng/ml peak, 61 +/- 5 ng/ml trough) exceeded the IC50 for platelet aggregation to adenosine diphosphate (ADP) (29 +/- 6 ng/ml) and thrombin-activating peptide (61 +/- 18 ng/ml). Orbofiban induced a conformational change in GPIIb/IIIa detected as the displacement of the monoclonal antibody mAb2; such conformational changes have been linked to partial agonist activity. Consistent with this, platelet expression of CD63 ex vivo was significantly increased at five time points during the study. In vitro, orbofiban increased platelet aggregation to a submaximal concentration of epinephrine (67 +/- 19% vs. 27 +/- 9%, n = 5) and increased thromboxane formation when the platelet GPIIb/IIIa were clustered using monoclonal antibodies to the receptor. CONCLUSIONS: Orbofiban is both an antagonist and a partial agonist of platelet GPIIb/IIIa. At low concentrations of the drug, this partial agonist activity may enhance platelet aggregation. Along with suboptimal plasma drug levels, these findings may help explain the lack of efficacy seen with orbofiban in patients with ACS.

Continued benefit of coronary stenting versus balloon angioplasty: one-year clinical follow-up of Benestent trial. Benestent Study Group.

OBJECTIVES: This study sought to determine the 1-year clinical follow-up of patients included in the Benestent trial. BACKGROUND: The Benestent trial is a randomized study comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in patients with stable angina and a de novo coronary artery lesion. Seven-month follow-up data have shown a decreased rate of restenosis and fewer clinical events in the stent group. It is not established whether this favorable clinical outcome is maintained for longer periods or whether coronary stenting defers restenosis and its subsequent clinical manifestations. METHODS: To clarify this uncertainty, we updated clinical information on all but 1 of 516 patients enrolled in the Benestent trial (257 in balloon group, 259 in stent group) at least 12 months after the intervention. Major clinical events (primary clinical end point) were tabulated according to the intention to treat principle and included death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for bypass surgery or a further percutaneous intervention in the previously treated lesion. RESULTS: After 1 year, no significant differences in mortality (1.2% vs. 0.8%), stroke (0.0% vs. 0.8%), myocardial infarction (5.0% vs. 4.2%) or coronary bypass graft surgery (6.9% vs. 5.1%) were found between the stent and balloon angioplasty groups, respectively. However, the requirement for a repeat angioplasty procedure was significantly lower in the stent group (10%) than the balloon angioplasty group (21%, relative risk [RR] 0.49, 95% confidence interval [CI] 0.31 to 0.75, p = 0.001), and overall primary end points were less frequently reached by stent group patients (23.2%) than those in the balloon group (31.5%, RR 0.74, 95% CI 0.55 to 0.98, p = 0.04). No differences were found between groups with respect to functional class angina and prescribed medication at the time of follow-up. CONCLUSIONS: These clinical follow-up data show that the benefit of elective native coronary artery stenting in patients with stable angina is maintained to at least 1 year after the procedure and results in a significantly reduced requirement for repeat intervention.

Cyclooxygenase-1 haplotype modulates platelet response to aspirin.

BACKGROUND: Aspirin (acetylsalicylic acid) irreversibly inhibits platelet cyclooxygenase (COX)-1, the enzyme that converts arachidonic acid (AA) to the potent platelet agonist thromboxane (TX) A2. Despite clear benefit from aspirin in patients with cardiovascular disease (CAD), evidence of heterogeneity in the way individuals respond has given rise to the concept of 'aspirin resistance.' AIMS: To evaluate the hypothesis that incomplete suppression of platelet COX as a consequence of variation in the COX-1 gene may affect aspirin response and thus contribute to aspirin resistance. PATIENTS AND METHODS: Aspirin response, determined by serum TXB2 levels and AA-induced platelet aggregation, was prospectively studied in patients (n = 144) with stable CAD taking aspirin (75-300 mg). Patients were genotyped for five single nucleotide polymorphisms in COX-1 [A-842G, C22T (R8W), G128A (Q41Q), C644A (G213G) and C714A (L237M)]. Haplotype frequencies and effect of haplotype on two platelet phenotypes were estimated by maximum likelihood. The four most common haplotypes were considered separately and less common haplotypes pooled. RESULTS: COX-1 haplotype was significantly associated with aspirin response determined by AA-induced platelet aggregation (P = 0.004; 4 d.f.). Serum TXB2 generation was also related to genotype (P = 0.02; 4 d.f.). CONCLUSION: Genetic variability in COX-1 appears to modulate both AA-induced platelet aggregation and thromboxane generation. Heterogeneity in the way patients respond to aspirin may in part reflect variation in COX-1 genotype.

The radial artery: an alternative access site for diagnostic and interventional coronary procedures.

BACKGROUND: Percutaneous techniques are routinely used in the diagnosis and treatment of cardiovascular disease. The transfemoral route is the most frequently used arterial access site for performing these procedures AIM: To describe a technique to gain arterial access via the radial artery to perform diagnostic and invasive procedures. METHODS: Patient selection is key to establishing a successful transradial service. RESULTS: There is a significant vascular complication rate when using the transfemoral route. Transfemoral access can also be difficult in patients with peripheral vascular disease. Arterial access via the right radial artery represents a realistic alternative to the transfemoral route for performing diagnostic and therapeutic coronary procedures. CONCLUSIONS: The radial artery offers a safe and effective alternative access site for performing diagnostic and interventional coronary procedures. The need for alternatives to femoral artery access is critical in patients with severe peripheral vascular disease. The establishment and ongoing provision of radial artery intervention allows for a significant reduction in major vascular complication rates, earlier patient ambulation, increased patient comfort and the potential to establish day case coronary intervention.

Impact of preexisting statin use on adhesion molecule expression in patients presenting with acute coronary syndromes.

Of 147 patients admitted with acute coronary syndromes, 17 were taking statins at the time of presentation. These were matched with 17 subjects not taking statins. We found that statin therapy was associated with lower levels of sP-selectin, a marker of platelet and vascular endothelial activation. This provides further insight into the extralipid effect of statins in clinical practice and may help explain the greater-than-expected benefits of statin therapy in ischemic heart disease.

Elevated levels of circulating soluble adhesion molecules in patients with nonrheumatic aortic stenosis.

Increased serum levels of soluble adhesion molecules are found in various disorders of inflammatory or immunologic etiology. We found elevated levels of the soluble adhesion molecules ICAM-1, VCAM-1, and E-selectin in patients with nonrheumatic aortic stenosis, suggesting that inflammation may be important in the pathogenesis of this condition, which is generally believed to be degenerative.

Early temporal expression of soluble cellular adhesion molecules in patients with unstable angina and subendocardial myocardial infarction.

Inflammation is increasingly considered to be involved in the pathogenesis of acute coronary syndromes. We documented persistent elevation in the levels of soluble ICAM-1 and soluble VCAM-1 and a decrease in the levels of soluble E-selectin in the first 72 hours of acute presentation in patients with unstable angina and subendocardial myocardial infarction.

Effects of verapamil in preventing early postinfarction angina and reinfarction.

Because verapamil is effective in the treatment of "preinfarction" angina, a single-blind, placebo-controlled trial was performed in 17 patients admitted to the coronary care unit with transmural acute myocardial infarction (AMI) to assess the effects of verapamil on angina and reinfarction after AMI. The study was terminated because results obtained in the initial 17 patients indicated that verapamil is not as effective in treating angina after AMI as it is in angina before AMI and does not prevent reinfarction. Continuous electrocardiographic monitoring during the first 3 days after AMI showed the presence of transient episodes of ST-segment elevation in 4 patients taking verapamil and 4 patients taking placebo. The total number and duration of transient ischemic episodes was similar in the 2 groups (46 vs 41 and 23 +/- 22 vs 17 +/- 15 minutes, respectively). The percentage of transient ischemic episodes accompanied by chest pain was similar in both groups (10%). The ischemic episodes were never preceded by important increases of heart rate. Four patients taking verapamil and 4 taking placebo had reinfarction within the first 10 days after the incident AMI. These findings suggest that the prevailing mechanisms of myocardial ischemia in the immediate post-AMI period could be different from those operating in angina before AMI.

Elevated levels of circulating soluble adhesion molecules in peripheral blood of patients with unstable angina.

We have demonstrated increased levels of the circulating soluble adhesion molecules (sCAMs), ICAM-1, VCAM-1, and E-selectin in patients with unstable angina compared with healthy controls. Our findings support the role of inflammation in clinically unstable coronary disease, and may indicate a potential role for measurement of peripheral sICAM levels as a marker for inflammatory activity in atherosclerotic plaque.