Hielko Miljoen

Coronary microvascular dysfunction after myocardial infarction: increased coronary zero flow pressure both in the infarcted and in the remote myocardium is mainly related to left ventricular filling pressure

Objective: To investigate the underlying mechanisms of a decreased coronary flow reserve after myocardial infarction (MI) by analysing the characteristics of the diastolic hyperaemic coronary pressure–flow relationship. Design: Prospective study. Setting: Tertiary care hospital. Patients: 68 patients with a recent MI and 27 patients with stable angina pectoris (AP; control group). Main outcome measures: The intercept with the pressure axis (the zero flow pressure or Pzf) and slope index of the pressure–flow relationship (SIPF) were calculated from the simultaneously recorded hyperaemic intracoronary blood flow velocity and aortic pressure after successful coronary stenting. Results: A stepwise increase in Pzf from AP (14.6 (8.0) mm Hg), over non-Q-wave MI (22.5 (9.1) mm Hg), to Q-wave MI (37.1 (12.9) mm Hg; p<0.001) was observed. Similar changes in Pzf were found in a reference artery perfusing the non-infarcted myocardium. Multivariate analysis showed that in both regions the left ventricular end-diastolic pressure (LVEDP) was the most important determinant of the Pzf. The SIPF was not statistically different in the treated vessel between patients with MI and AP, but was increased in MI patients with a markedly increased LVEDP. Conclusions: After an MI, the coronary pressure–flow relationship is shifted to the right both in the infarcted and in the non-infarcted remote myocardium, as shown by the increased Pzf. The correlation with Pzf suggests that elevated left ventricular filling pressures contribute to the impediment of myocardial perfusion in patients with infarction.

The effect of endurance training on exercise capacity following cardiac resynchronization therapy in chronic heart failure patients: a pilot trial

Background Both endurance training (ET) and cardiac resynchronization therapy (CRT) improve quality of life (QOL) and exercise tolerance in patients with advanced chronic heart failure (CHF). Design A randomized intervention trial to study the effect on exercise capacity of ET in addition to CRT in patients with CHF and dyssynchrony. Methods Seventeen patients (eight men, aged 59 ± 9 years) with CHF and dyssynchrony were randomized to CRT with (n = 8) or without (n = 9) ET and compared with two matched control CHF groups (standard care with ET: n = 9, standard care only: n = 10). At baseline and after 5 months, exercise tolerance, left ventricular (LV) remodelling, QOL and NT-pro brain natriuretic peptide (NT-proBNP) levels were assessed. Results Peak oxygen consumption (VO2peak), maximal workload (Wattmax), circulatory power, LV ejection fraction, dyssynchrony and QOL improved in both CRT groups. However, the increase in VO2peak (+ 40% versus +16%, P = 0.005), Wattmax (+ 43% versus +13%, P = 0.0005), and circulatory power (+ 74% versus + 32%, P = 0.01), was significantly greater in the trained versus the untrained CRT patients. Comparison of the four patient groups confirmed the cumulative effects of CRT plus ET. Conclusions ET in resynchronized CHF patients is feasible and further enhances exercise tolerance. Patients with severe CHF should be prescribed an exercise training programme after implantation in order to maximize the expected benefit. Eur J Cardiovasc Prev Rehabil 14: 99-106

The Role of Nurses in a Chest Pain Unit

The chest pain unit (CPU) provides a service for patients at moderate-to-low risk for acute coronary syndrome (ACS). Although the number of CPUs has continued to grow worldwide, little has been written on the specific role and contribution of nursing in CPUs. The stay of patients in the CPU can be divided into six stages: triage, diagnosis, treatment, observation/monitoring, discharge, and follow-up. CPU nurses are in a unique position to promote evidence-based practice during all of these stages. Deeper insight into the unique role of nurses in CPUs will promote understanding of what type of knowledge, skills, and attitudes are required to provide the services that will contribute to improved quality of care for chest pain patients.

Implementation of the guidelines for the management of patients with chest pain through a critical pathway approach improves length of stay and patient satisfaction but not anxiety.

OBJECTIVE To compare length of stay (LOS), clinical and psychological outcomes, and patient satisfaction before and after implementation of a chest pain critical pathway. DESIGN A pre- and post-test quasi-experimental design. SETTING The Chest Pain Unit (CPU) of the Antwerp University Hospital. PATIENTS Patients admitted to the CPU with symptoms suggestive of an acute coronary syndrome older than 18 years. INTERVENTIONS Implementation of a critical pathway focusing on implementation of the guidelines for the management of chest pain. MAIN OUTCOME MEASURES Patient satisfaction, length of stay and anxiety were evaluated. RESULTS The median LOS of intervention subjects was almost 4 hours shorter than that of control subjects (without, P = 0.04, or with propensity correction, P = 0.019). The overall patient satisfaction with CPU care of the intervention group was significantly higher than that of the control group (without, P < 0.001, or with propensity correction, P < 0.001). Differences in anxiety and occurrences of major adverse cardiac events between the groups were not statistically significant. CONCLUSION A critical pathway can effectively and safely reduce LOS, increase patient satisfaction, and improve adherence to the guidelines for managing patients with chest pain. Anxiety is not statistically significantly reduced by this intervention.

Impaired coronary flow reserve after a recent myocardial infarction: Correlation with infarct size and extent of microvascular obstruction

BACKGROUND The exact relationship between the coronary flow reserve (CFR) and infarct size remains unknown. In this prospective study the relationship between the CFR both in the infarcted and remote myocardium and infarct size was investigated. Furthermore, the diagnostic value of the CFR to predict the extent of microvascular obstruction (MO) was evaluated. METHODS In thirty patients the CFR was measured with a Doppler guide wire 6 ± 3 days after a first myocardial infarction (MI) in the infarct related and in a reference coronary artery. MO and infarct size were determined with magnetic resonance imaging. RESULTS The CFR was inversely related to infarct size in the infarcted and remote myocardium (respectively, r=-0.60, p<0.01 and r=-0.62, p<0.01). In the infarcted myocardium the extent of MO was strongly related to the infarct size and was in a multivariate analysis the single significant determinant of the CFR and the hyperaemic flow. In the remote myocardium no relationship was present between infarct size and hyperaemic flow, but the baseline flow increased as the infarct size became larger (r=0.58, p<0.01). In a receiver operator characteristic (ROC) analysis, a CFR value ≤ 2 in the infarct related coronary artery offered the best sensitivity (65%) and specificity (71%) to detect the presence of MO (p<0.05). CONCLUSIONS After MI, the CFR both in the infarcted and remote myocardium is inversely related to infarct size. In the infarcted myocardium, a CFR value ≤ 2 predicts the presence of MO with moderate sensitivity and specificity.

Adiponectin and ischemia-reperfusion injury in ST segment elevation myocardial infarction

Background: Models of experimental ischemia-reperfusion (IR) in adiponectin knockout animals have shown that adiponectin mediates protection against the development of IR injury. However, the role of adiponectin in IR injury in humans is largely unknown. Methods: In a total of 234 ST segment elevation myocardial infarction (STEMI) patients, baseline circulating total adiponectin concentration was correlated with IR injury after primary percutaneous coronary intervention (pPCI) and with major adverse cardiac events (MACE, death and cardiac hospitalization) during one year of follow up. IR injury was defined by serial electrocardiography (ECG) as >30% persistent ST segment elevation despite successful restoration of vessel patency and by angiography as thrombolysis in myocardial infarction (TIMI) blush grade<2. Results: IR injury was present in 31% of patients according to ECG criteria and in 28% of patients according to angiographic criteria. The median adiponectin level was 6.8 µg/ml in patients with ECG signs of IR injury and 6.5 µg/ml in patients without ECG signs of IR (p=0.26). When the angiographic criteria of IR were used, the median adiponectin level was 6.9 µg/ml for patients with IR versus 6.3 µg/ml for patients without IR (p=0.06). MACE occurred in 27% of the patients. Median adiponectin levels were similar in patients with MACE and in those without MACE: 6.3 vs. 6.4 µg/ml (p=0.24). In a multivariate model, no significant relation between circulating adiponectin levels and IR injury or MACE was evident. Conclusion: In the current era of pPCI, IR injury still occurs in almost one third of STEMI patients. Our findings do not support a major protective role of adiponectin in the prevention or attenuation of IR injury in these patients.

Clinical relevance of clopidogrel unresponsiveness during elective coronary stenting: Experience with the point-of-care Platelet Function Assay–100 C/ADP

BACKGROUND Early identification of nonresponders to clopidogrel may be important in identifying subgroups of patients that might be at risk for future thrombotic events. METHODS We prospectively assessed postclopidogrel platelet reactivity in 250 consecutive patients scheduled for elective percutaneous coronary intervention (PCI). All patients received dual antiplatelet therapy with 160 mg aspirin and a 300 mg loading dose of clopidogrel >12 hours before PCI. A platelet aggregation test was performed at the time of the intervention using a point-of-care assay, the Platelet Function Assay (PFA-100C/ADP; Dade-Behring, Deerfield, IL). Nonresponders were defined as having a PFA closure time of <71 seconds under dual oral antiplatelet therapy, reflecting normal platelet reactivity. Myonecrosis post-PCI constituted the primary end point and was defined as the release of creatine kinase-MB >1x the upper limit of normal on a sample taken 12 to 24 hours after intervention. The secondary end point was a composite end point of major adverse cardiac events including death, myocardial infarction, and stent thrombosis after 6 months. RESULTS The PFA closure time was available in 242 patients and ranged from 31 to 300 seconds with a mean value of 147 seconds. Nonresponders represented 7% (17/242) of the cases. Myonecrosis post-PCI occurred in 29 patients (12%) and was more common in nonresponders than in normal responders (29% vs 11%, respectively; P = .03 on multivariate analysis). Major adverse cardiac events at 6 months occurred in 13 patients (1 sudden death possibly related to stent thrombosis and 12 post-PCI myocardial infarctions) and were more common in the nonresponder group (12% vs 5%, respectively; P = .06 on multivariate analysis). CONCLUSIONS Unresponsiveness to clopidogrel as assessed by the point-of-care test PFA-100C/ADP is an independent major risk factor for thrombotic complications after coronary intervention.

Levels of Circulating CD34+/KDR+ Cells Do Not Predict Coronary In-Stent Restenosis

BACKGROUND Angiographic and clinical parameters are poor predictors of in-stent restenosis. Bone marrow-derived CD34(+) cells that coexpress a receptor for vascular endothelial growth factor (kinase insert domain receptor [KDR]) are committed to endothelial lineage. Mobilization and infusion of CD34(+)/KDR(+) cells accelerates re-endothelialization and reduces neointimal thickness in vascular injury models. Bioengineered stents capturing CD34(+) cells also show expedited re-endothelialization. We examined whether circulating CD34(+)/KDR(+) cell counts can be used to predict restenosis in a bare-metal stent (BMS). METHODS CD34(+)/KDR(+) cells were counted by flow cytometry in 124 nondiabetic patients before BMS implantation and the relation to in-stent late luminal loss (LLL) was examined by angiography at 6 months (primary end point). Neointima was also quantified as the maximum percentage area stenosis (M%AS) and percentage volume intima hyperplasia (%VIH) on intravascular ultrasonography (secondary end points). RESULTS Multiple linear regression analysis, taking into account implanted stent length and diameter, revealed no relation between CD34(+)/KDR(+) cell counts and LLL (partial regression coefficient b = 0.11; 95% confidence interval [CI], -0.19-0.42; P = 0.46). Similarly, no relation between CD34(+)/KDR(+) cell counts and M%AS or %VIH could be demonstrated. Moreover, the increase in CD34(+)/KDR(+) cell counts over 6 months was unrelated to LLL (b = -0.15; 95% CI, -0.42-0.12; P = 0.28), M%AS, and %VIH. CONCLUSIONS Although our study does not exclude a pathophysiologic role for CD34(+)/KDR(+) cells in the formation of neointima, cell counts before percutaneous coronary intervention proved to be unrelated to LLL or intravascular ultrasonographically derived restenosis parameters in coronary BMSs at 6 months.

Prospective study of tricuspid valve regurgitation associated with permanent leads in patients undergoing cardiac rhythm device implantation: Background, rationale, and design

Given the increasing numbers of cardiac device implantations worldwide, it is important to determine whether permanent endocardial leads across the tricuspid valve can promote tricuspid regurgitation (TR). Virtually all current data is retrospective, and indicates a signal of TR being increased after permanent lead implantation. However, the precise incidence of moderate or greater TR post-procedure, the exact mechanisms (mechanical, traumatic, functional), and the hemodynamic burden and clinical effects of this putative increase in TR, remain uncertain. We have therefore designed a multicenter, international, prospective study of 300 consecutive patients (recruitment completed, baseline data presented) who will undergo echocardiography and clinical assessment prior to, and at 1-year post device insertion. This prospective study will help determine whether cardiac device-associated TR is real, what are its potential mechanisms, and whether it has an important clinical impact on cardiac device patients.

Gastroenteritis with severe consequences: a case of sotalol-induced torsades de pointes

We present a case of sotalol-induced prolongation of the QT-interval with torsades de pointes in an octogenarian who was hospitalized because of gastroenteritis causing prerenal acute renal failure. Subsequent accumulation of sotalol caused a severe prolongation of the QT-interval on the surface ECG and ultimately torsades de pointes with loss of consciousness. The patient was successfully treated with temporary cardiac pacing, intravenous magnesium sulfate and definitive withdrawal of sotalol.The electrophysiological basis of the pro-arrhythmic properties of sotalol is reviewed in brief, additional risk factors are identified and treatment is outlined.