Risk Of Cardiac Ischemic Events Research Articles

Exercise ECG and myocardial perfusion SPECT show high prognostic value up to four years after examination

Abstract Background Abnormal results of myocardial perfusion SPECT (MPS) or exercise ECG (Ex-ECG) is known to be associated with increased risk of ischemic cardiac events. The predictive value of stress testing however, is influenced by underlying risk factors as well as follow up duration and may vary considerably over time. With traditional Cox proportional hazards analysis the time-varying effects are not sufficiently accounted for. Purpose To evaluate the prognostic longevity of MPS and Ex-ECG using statistical methods that allow hazard ratio changes over time. Methods 908 patients (age 63 years, 49% male, 45% prior ischemic heart disease (IHD)) referred for MPS were prospectively included. Ex-ECG was performed in conjunction with MPS. Registry data were used for follow up. The outcome was a composite of acute myocardial infarction, unstable angina, unplanned revascularization, and cardiovascular death. Cox proportional hazard analysis and smoothed hazard functions with splines were used for risk assessment during follow up. Results Ex-ECG or MPS were abnormal in 198 (22%) or 148 (16%) of patients respectively. The mean follow up time was 8.2±2.6 years and the composite end point was reached in 189 patients (21%). The Kaplan-Meier curves suggest an interaction with time with the risk of event for subjects with abnormal test results being highest in the 2-3 of years after which the curves are approximately parallel (Figure 1). In multivariable models the best fit (lowest Akaike information criterion (AIC) value) was obtained with a logarithmic interaction term for time. With this approach and controlling for known risk factors the hazard ratio (HR) drops to 1 after approximately four years for both Ex-ECG and MPS (Figure 2). Age (HR=1.04, p<0.001), sex (HR=2.0, p<0.001), IHD (HR=1.7, p<0.001) and reduced exercise capacity (HR=0.99, p<0.001) were independent significant predictors of risk. Conclusions The high risk associated with abnormal MPS and Ex-ECG results decrease rapidly over time and after approximately 4 years the predictive value is lost. Thus, the long-term impact on prognosis of stress testing appear questionable. The time-varying effects on risk are substantial and warrant statistical considerations when designing clinical follow up studies of chronic coronary syndrome.

Direct Oral Anticoagulants Versus Vitamin-K Antagonist After PCIs in Patients With AF: A Meta-analysis of Cardiac Ischemic Events.

Clinical trials have assessed the effect of direct oral antagonists (DOACs) in patients with atrial fibrillation (AF) after percutaneous coronary interventions (PCI). Studies were designed to test the effect on bleeding incidence, but concerns related to safety on ischemic events remain. We performed a meta-analysis with currently available studies involving DOACs versus Vitamin-K antagonist (VKA) in patients with AF after PCI. The primary endpoint was the incidence of cardiac ischemic events, including myocardial infarction and stent thrombosis. Secondary endpoints were the incidence of stroke, all-cause mortality, and major bleeding. Eleven thousand twenty-three patients were included in the analysis: 5510 receiving DOACs and 5513 VKA. A total of 190 cases of myocardial infarction were registered in patients treated with DOACs and 177 in patients on VKA, and no statistical difference was noted [relative risk (RR): 1.07 95% confidence interval (CI) 0.88-1.31]. The incidence of stent thrombosis was very low with no differences between both treatment strategies (RR: 1.14 95% CI 0.76-1.71). The incidence of cardiac ischemic events was the same in patients receiving DOACs or VKA (HR 1.09 95% CI 0.91-1.30). No differences were observed in the incidence of stroke (RR: 0.86 95% CI 0.61-1.23) or mortality (RR: 1.09, 95% CI 0.90-1.31). Treatment with DOACs was associated with 34% reduction in major bleeding (RR: 0.66, 95% CI 0.54-0.81). Treatment with DOACs in patients with AF after a PCI do not increase the risk of cardiac ischemic events, stroke, or death and reduce the incidence of major bleeding by 34% as compared with VKA.

Prognostic Value of the Residual SYNTAX Score on In-Hospital and Follow-Up Clinical Outcomes in ST Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Interventions.

Aims We investigated the prognostic significance of residual SYNTAX score (RSS) in patients undergoing PCI due to STEMI and relationship between RSS and in-hospital and long-term ischemic cardiac events. Methods Between June 2015 and December 2018, 538 patients who underwent primary PCI were evaluated for in-hospital events and 478 patients were evaluated for clinical events during follow-up. Primary and secondary endpoints for both in-hospital and follow-up periods were cardiac death and major adverse cardiac events (MACE). Results 538 patients were included the study. RSS values of 131 patients were 0, and RSS values of 407 patients were >0. The median value of the RSS > 0 group was 7. According to this value, the RSS > 0 group was divided into 2 groups as R-ICR (RSS < 7, N = 188) and ICR (RSS ≥ 7, n = 219). In the RSS ≥ 7 group, during in-hospital and follow-up period, both mortality and MACE rates were higher than the other two groups. Area under the curve (AUC) for RSS for in-hospital death was found to be higher than SS (p=0.035) but similar to Grace Score (GS) (p=0.651). For MACE, RSS was higher than SS (p=0.025) and higher than the GS (p=0.041). For follow-up cardiac mortality, the AUC of the RSS was found to be higher than SS (0.870/0.763, p=0.02) and GS (0.870/0.733, p=0.001). For MACE, the AUC of RSS was higher than SS (p=0.03) and GS (p=0.004). Conclusions High RSS values in STEMI patients are associated with increased risk of ischemic cardiac events. RSS may help determine revascularization and level of additional PCI to improve prognosis by reducing the risk of ischemic cardiac events after P-PCI.

Aldosterone impairs coronary adenosine-mediated vasodilation via reduced functional expression of Ca2+-activated K+ channels

Elevated plasma aldosterone (Aldo) levels are associated with greater risk of cardiac ischemic events and cardiovascular mortality. Adenosine-mediated coronary vasodilation is a critical cardioprotective mechanism during ischemia; however, whether this response is impaired by increased Aldo is unclear. We hypothesized that chronic Aldo impairs coronary adenosine-mediated vasodilation via downregulation of vascular K+ channels. Male C57BL/6J mice were treated with vehicle (Con) or subpressor Aldo for 4 wk. Coronary artery function, assessed by wire myography, revealed Aldo-induced reductions in vasodilation to adenosine and the endothelium-dependent vasodilator acetylcholine but not to the nitric oxide donor sodium nitroprusside. Coronary vasoconstriction to endothelin-1 and the thromboxane A2 mimetic U-46619 was unchanged by Aldo. Additional mechanistic studies revealed impaired adenosine A2A, not A2B, receptor-dependent vasodilation by Aldo with a tendency for Aldo-induced reduction of coronary A2A gene expression. Adenylate cyclase inhibition attenuated coronary adenosine dilation but did not eliminate group differences, and adenosine-stimulated vascular cAMP production was similar between Con and Aldo mice. Similarly, blockade of inward rectifier K+ channels reduced but did not eliminate group differences in adenosine dilation whereas group differences were eliminated by blockade of Ca2+-activated K+ (KCa) channels that blunted and abrogated adenosine and A2A-dependent dilation, respectively. Gene expression of several coronary KCa channels was reduced by Aldo. Together, these data demonstrate Aldo-induced impairment of adenosine-mediated coronary vasodilation involving blunted A2A-KCa-dependent vasodilation, independent of blood pressure, providing important insights into the link between plasma Aldo and cardiac mortality and rationale for aldosterone antagonist use to preserve coronary microvascular function.NEW & NOTEWORTHY Increased plasma aldosterone levels are associated with worsened cardiac outcomes in diverse patient groups by unclear mechanisms. We identified that, in male mice, elevated aldosterone impairs coronary adenosine-mediated vasodilation, an important cardioprotective mechanism. This aldosterone-induced impairment involves reduced adenosine A2A, not A2B, receptor-dependent vasodilation associated with downregulation of coronary KCa channels and does not involve altered adenylate cyclase/cAMP signaling. Importantly, this effect of aldosterone occurred independent of changes in coronary vasoconstrictor responsiveness and blood pressure.

Bloqueio perioperatório do plexo lombar e isquemia cardíaca em pacientes com fratura de quadril: ensaio clínico randomizado

BackgroundPerioperative myocardial ischemia is common among patients undergoing hip fracture surgery. Our aim is to evaluate the efficacy of perioperative continuous lumbar plexus block in reducing the risk of cardiac ischemic events of elderly patients undergoing surgery for hip fractures, expressed as a reduction of ischemic events per subject. MethodsPatients older than 60 years, ASA II–III, with risk factors for or known coronary artery disease were enrolled in this randomized controlled study. Patients were randomized to conventional analgesia using opioid intravenous patient‐controlled analgesia or continuous lumbar plexus block analgesia, both started preoperatively and maintained until postoperative day three. Continuous electrocardiogram monitoring with ST segment analysis was recorded. Serial cardiac enzymes and pain scores were registered during the entire period. We measured the incidence of ischemic events per subject registered by a continuous ST‐segment Holter monitoring. ResultsThirty‐one patients (intravenous patient‐controlled analgesia 14, lumbar plexus 17) were enrolled. There were no major cardiac events during the observation period. The number of ischemic events recorded by subject during the observation period was 6 in the lumbar plexus group and 3 in the intravenous patient‐controlled analgesia group. This difference was not statistically significant (p=0.618). There were no statistically significant differences in the number of cases with increased perioperative troponin values (3 cases in the lumbar plexus group and 1 case in the intravenous patient‐controlled analgesia group) or in terms of pain scores. ConclusionsUsing continuous perineural analgesia, compared with conventional systemic analgesia, does not modify the incidence of perioperative cardiac ischemic events of elderly patients with hip fracture.

Randomized Comparisons of Double-Dose Clopidogrel or Adjunctive Cilostazol Versus Standard Dual Antiplatelet in Patients With High Posttreatment Platelet Reactivity: Results of the CREATIVE Trial.

Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs. Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events. The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE]) and conventional strategy (STANDARD) in patients after percutaneous coronary intervention. In this single-center, randomized, controlled trial, we used thromboelastography, a platelet function test, to select 1078 patients undergoing percutaneous coronary intervention at high thrombotic risk and compared the intensified antiplatelet therapies with standard antiplatelet therapy. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events at 18 months after percutaneous coronary intervention, defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, or stroke. Bleeding Academic Research Consortium defined bleeding complications (types 1, 2, 3, or 5) were the safety end points. The primary end point occurred in 52 patients (14.4%) in the STANDARD group, 38 patients (10.6%) in the DOUBLE group, and 30 patients (8.5%) in the TRIPLE group (hazard ratio, 0.720; 95% confidence interval, 0.474-1.094, DOUBLE versus STANDARD; hazard ratio, 0.550; 95% confidence interval, 0.349-0.866, TRIPLE versus STANDARD). No significant difference in the rates of major bleeding (Bleeding Academic Research Consortium grade≥3) was found in the DOUBLE group (3.34% versus 1.93% in STANDARD, P=0.133) and the TRIPLE group (2.53% versus 1.93% in STANDARD, P=0.240). The rate of Bleeding Academic Research Consortium-defined minor bleeding increased in the DOUBLE group (27.4% versus 20.3% in STANDARD, P=0.031), but not in the TRIPLE group (23.6% versus 20.3% in STANDARD, P=0.146). In patients with low responsiveness to clopidogrel, as measured by thromboelastography, the intensified antiplatelet strategies with adjunctive use of cilostazol significantly improved the clinical outcomes without increasing the risk of major bleeding. Decreased trend of negative outcomes could be observed in patients with double dosage of clopidogrel, but the difference was not significant. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01779401.

Perioperative lumbar plexus block and cardiac ischemia in patients with hip fracture: randomized clinical trial

BackgroundPerioperative myocardial ischemia is common among patients undergoing hip fracture surgery. Our aim is to evaluate the efficacy of perioperative continuous lumbar plexus block in reducing the risk of cardiac ischemic events of elderly patients undergoing surgery for hip fractures, expressed as a reduction of ischemic events per subject. MethodsPatients older than 60 years, ASA II–III, with risk factors for or known coronary artery disease were enrolled in this randomized controlled study. Patients were randomized to conventional analgesia using opioid intravenous patient-controlled analgesia or continuous lumbar plexus block analgesia, both started preoperatively and maintained until postoperative day three. Continuous electrocardiogram monitoring with ST segment analysis was recorded. Serial cardiac enzymes and pain scores were registered during the entire period. We measured the incidence of ischemic events per subject registered by a continuous ST-segment Holter monitoring. ResultsThirty-one patients (intravenous patient-controlled analgesia 14, lumbar plexus 17) were enrolled. There were no major cardiac events during the observation period. The number of ischemic events recorded by subject during the observation period was 6 in the lumbar plexus group and 3 in the intravenous patient-controlled analgesia group. This difference was not statistically significant (p=0.618). There were no statistically significant differences in the number of cases with increased perioperative troponin values (3 cases in the lumbar plexus group and 1 case in the intravenous patient-controlled analgesia group) or in terms of pain scores. ConclusionsUsing continuous perineural analgesia, compared with conventional systemic analgesia, does not modify the incidence of perioperative cardiac ischemic events of elderly patients with hip fracture.

High-fat diet induces metabolic changes and reduces oxidative stress in female mouse hearts

After an acute myocardial infarction, obese patients generally have a better prognosis than their leaner counterparts, known as the “obesity paradox”. In addition, female sex is associated with a lower risk of cardiac ischemic events and smaller infarct size compared to males. The objective of the present work was to study the metabolic phenotype and mitochondrial function associated to female sex and short-term high-fat diet. 1H NMR spectra of mice heart extracts were analysed by mRMR variable selection and linear discriminant analysis was used to evaluate metabolic changes. In separate experiments, O2 consumption and H2O2 production were measured from isolated mitochondria as well as serum oxidation susceptibility. Fingerprinting showed that male hearts contained more myo-inositol, taurine and glutamate than female hearts. HFD reduced the levels of creatine, taurine citrate and acetate. Profiling showed increased alanine and fumarate in HFD suggesting altered glycolitic and Krebs cycle pathways. Female mice contained less glucose than males. Female sex nor HFD altered mitochondria oxygen consumption but both conditions reduced the amount of H2O2 produced in an additive manner. Serum of females had lower oxidation susceptibility than serum from males but there were no differences associated with HFD. In conclusion, female sex and short-term HFD have an effect on the myocardial metabolic pattern and reduce the amount of H2O2 produced by mitochondria in an additive manner suggesting different mechanisms of action. This could explain, at least in part, the protection afforded by female sex and the “obesity paradox”.

Ischemic cardiac outcomes and hospitalizations according to prior macrovascular disease status in patients with type 2 diabetes and recent acute coronary syndrome from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care trial

Concerns raised regarding adverse cardiovascular (CV) outcomes with new therapies for type 2 diabetes mellitus (T2DM) have led to several large-scale CV outcome trials. The EXAMINE trial confirmed noninferiority of the dipeptidyl dipeptidase 4 inhibitor alogliptin to placebo on major adverse cardiac event rates in a post-acute coronary syndrome (ACS) T2DM population. We present data on additional ischemic cardiac events and CV hospitalizations in EXAMINE. Patients with T2DM and an ACS event in the previous 15 to 90 days were randomly assigned to alogliptin or placebo on a background of standard treatment for diabetes. The incident rates of a 5-component composite end point of CV death, stroke, myocardial infarction, unstable angina, and coronary revascularization as well as CV hospitalization were calculated in all participants and according to macrovascular disease at baseline. There were no significant differences between alogliptin (n = 2,701) and placebo (n = 2,679) in the event rate of the 5-component composite endpoint with median follow-up 533 days (21.0% vs 21.5%, hazard ratio [HR] 0.98 [0.87-1.10], P = .72). No differences were observed in terms of CV hospitalization (25.0% vs 25.4%, HR 0.98 [0.88-1.09], P = .70) or coronary revascularization (10.6% vs 10.2%, HR 1.05 [0.88-1.09], P = .60). No interactions were observed for treatment and prior macrovascular disease. EXAMINE demonstrates that there was no increase in the risk of cardiac ischemic events and CV hospitalizations with alogliptin in a high-risk post-ACS patient population. Because these are major driver of overall health care costs, these data suggest that there would be no adverse impact on health care resource utilization.

194 - Mesna (Sodium-2-Mercaptoethane Sulfonate) Modulates the Catalytic Activity of Lactoperoxidase

Increasing numbers of total joint arthroplasty (TJA) patients have a history, or an active diagnosis, of cancer. We aimed to evaluate the risk of early postoperative complications in these patients. In our series, a history of malignancy was associated with an elevated risk of ischemic cardiac events and postoperative deep vein thrombosis (DVT), while active malignancy was associated with increased respiratory and renal complications, hematoma/seroma formation and early postoperative mortality. Both groups presented increased rates of overall in-hospital complications. Patients with bone metastasis to the hip demonstrated increased DVT and 90-day mortality rates. Cancer patients have increased morbidity and mortality after TJA and should undergo comprehensive medical optimization and adapted thromboprophylaxis.

Abstract P1-15-01: Association between ischemic cardiac events and targeting of the internal mammary nodal region with adjuvant radiation for breast cancer

Abstract Background: Cardiac toxicity has been well documented following adjuvant breast cancer radiation therapy (RT) using outdated treatment methods. Limited information exists, however, regarding cardiac outcomes following contemporary RT fields and techniques. Inclusion of the internal mammary nodal (IMN) field for appropriately selected patients with breast cancer coincided with our department’s transition to computed-tomography (CT) based planning. The objectives of this study, therefore, were to assess the risk of ischemic cardiac events following IMN irradiation and to assess the risks following CT-based versus two-dimensional (2D) planning. Methods: All patients treated with adjuvant RT for breast cancer and without history of additional chest RT from January 1, 1984 – December 31, 2007 in our department were assessed. CT planning for breast cancer began for select patients in 1997 and was used for all patients as of 2001. The inclusion of the IMN region was determined by review of our clinical database. Ischemic cardiac endpoints were defined as myocardial infarction, coronary artery bypass grafting procedure, angioplasty/stent placement, and/or diagnosis of coronary artery disease. A text-based and diagnosis code-based search was used to flag possible endpoints which were then confirmed by manual chart review. Hypertension (HTN), diabetes (DM), hyperlipidemia (HLD), and anthracycline use were identified by a diagnosis code-based search. Results: We identified 2,126 patients who received adjuvant RT. Median follow-up was 9.6 years. 311 (14.6%) patients had IMNs targeted and 1,813 (85.3%) did not (data not available for 2 patients). RT to the IMNs was not associated with a higher risk of ischemic cardiac events (HR: 0.88, P = 0.731). 1,072 (50.4%) patients had CT planning, 1,003 (47.2%) had 2D planning, and no information was available for 51 (2.4%) patients. Overall, there were 56 (5.6%) ischemic events in the 2D cohort and 27 (2.5%) in the CT cohort. After truncating follow-up to 10 years to account for differential potential follow-up, there were 28 (2.8%) and 23 (2.2%) ischemic cardiac events, respectively. The table lists the association of patient and treatment characteristics and risk of ischemic cardiac events. HTN, HLD, and DM were each associated with a significantly increased risk of ischemic cardiac events. Conclusions: After reviewing all patients treated in our department for breast cancer from 1984 – 2007, we were unable to find an association between IMN irradiation and ischemic cardiac events. CT-based planning has been shown to allow accurate targeting of the IMNs. These data suggest that even with inclusion of the IMNs, CT-based planning minimizes dose to the heart and coronary arteries thereby decreasing the risk of ischemic cardiac toxicity. These results will be followed with time. Association between characteristics and ischemic cardiac eventsCharacteristicHazard Ratio95% Confidence IntervalP-valueRT to the IMNs0.880.42-1.830.7312D vs. CT planning1.140.68-1.910.613Left vs. right1.210.79-1.850.372Anthracycline use0.750.44-1.260.270HTN5.612.06-15.300.001HLD1.901.25-2.900.003DM3.111.99-4.86&amp;lt;0.001 Citation Format: Adam L Liss, Kent A Griffith, Reshma Jagsi, Jean M Moran, Robin B Marsh, Todd M Koelling, Lori J Pierce. Association between ischemic cardiac events and targeting of the internal mammary nodal region with adjuvant radiation for breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-01.

Total joint arthroplasty in cancer patients

Increasing numbers of total joint arthroplasty (TJA) patients have a history, or an active diagnosis, of cancer. We aimed to evaluate the risk of early postoperative complications in these patients. In our series, a history of malignancy was associated with an elevated risk of ischemic cardiac events and postoperative deep vein thrombosis (DVT), while active malignancy was associated with increased respiratory and renal complications, hematoma/seroma formation and early postoperative mortality. Both groups presented increased rates of overall in-hospital complications. Patients with bone metastasis to the hip demonstrated increased DVT and 90-day mortality rates. Cancer patients have increased morbidity and mortality after TJA and should undergo comprehensive medical optimization and adapted thromboprophylaxis.

ATRIAL FIBRILLATION IN STEMI PATIENTS: CONTEMPORARY MANAGEMENT AND ONE YEAR OUTCOMES

abetics, 19% Killip 4, and 77% undergoing primary PCI. The proportions taking 4/4 medication classes at discharge were 73.6% and 75.5% in intervention and control arms, respectively. At 12 months, proportions were 58.4% and 58.9% in the intervention and control group, respectively, (model-based OR 1.1, 95% CI 0.83-1.45). The process evaluation indicates that 51% of patients remembered receiving the intervention, and of these 52% took it for discussion with their health care provider. Patients reported that discontinuation of medication was most commonly at the direction of the internist/cardiologist (64%), and due to medication-related side-effects (62%). Discussion: DERLA-STEMI demonstrates the feasibility of recruiting and randomizing all eligible STEMI patients in a provincial health region. Preliminary results suggest low persistence to all 4 cardiac medication classes at 12-months. There was no significant difference in the use of guidelinerecommended medications post-STEMI in patients (and their family physicians) receiving delayed and repeated reminders as compared to usual care. HHS

Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers.

In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane).

Aortic Valve Replacement and Concomitant Coronary Artery Bypass Grafting in a Patient with Infective Endocarditis and Anomalous Origin of the Right Coronary Artery from the Opposite Sinus of Valsalva

A 69-yrs-old woman with anomalous origin of the right coronary artery from the opposite sinus of Valsalva (ACAOS) was diagnosed as having infective endocarditis affecting the aortic valve. Transthoracic echocardiography showed severe aortic stenosis and vegetations on the cusp of the aortic valve, which necessitated aortic valve replacement. Before the operation, computed tomography showed a right-ACAOS, with the artery running an interarterial course between the aorta and pulmonary artery. ACAOS running an interarterial course has been reported to be associated with an increased risk of ischemic cardiac events and sudden death. The patient was treated successfully by the aortic valve replacement with concurrent coronary artery bypass grafting using a saphenous vein graft for the right coronary artery.

Viability Tested with Dobutamine Stress Echocardiography and Prognosis Early after Acute Myocardial Infarction: A Meta-Analysis

In non-high risk patients treated without primary PCI for acute myocardial infarction (AMI), the updated American Heart Association/American College of Cardiology guidelines recommend a selective pharmacoinvasive strategy (IIb, level C). Early risk assessment is essential to select patients with an increased risk for ischemic events or cardiac death. A potential prognostic value has been ascribed to viability in the infarct region. Viability-testing with Low Dose Dobutamine echocardiography (LDDE) can safely be performed in the early phase after AMI. Since the prognostic value of viability after acute myocardial infarction remains unclear and is still debated, we performed a meta-analysis of post-infarction studies to elucidate the importance and prognostic value of viability early after AMI. The literature was scanned by formal searches of electronic databases from 1966 to June 2010. We used the following selection criteria for inclusion in this meta-analysis: a) viability testing with LDDE within 14 days after Acute Myocardial Infarction (AMI), b) preserved left ventricular function (ejection fraction(EF) ≥40% or wall motion score index (WMSI) ≤1.9), c) prognosis scored by clinical endpoints (death, AMI or unstable angina (UA)). Eight observational studies were included in the meta-analysis (2301 patients). Results: The presence of viability was strongly associated with an increase in ischemic cardiac events [OR 5.0 (1.53 - 16.36), p=0.008]. No predictive value was found for mortality [OR 0.91 (0.38 - 2.18), p=0.84]. In conclusion, patients with preserved left ventricular function and proven viability early after AMI are at risk for ischemic cardiac events, without any difference in mortality (Metaanalysis, acute myocardial infarction, viability, echocardiography).

The association between migraine and cardiovascular events in women is modified by baseline vascular risk status

Introduction: Migraine has been associated with increased risk of ischemic stroke, particularly in women [1–4]. This association is more evident for migraine with aura (MA) than for migraine without aura (MO) [1,5]. Neuroimaging studies have found higher prevalence of silent cerebellar infarcts in migraineurs compared with controls, and an increased number of white matter lesions in women with migraine [6]. Migraine also has been associated with an increased risk of cardiac ischemic events in both women and men [7,8]. Several mechanisms for these associations have been proposed, including vasospasm, endothelial dysfunction, and increased platelet aggregation [9,10]. In a large population-based study, migraine patients—in particular those with MA—were more likely to have unfavorable cardiovascular risk profi les compared with controls [11]. Patent foramen ovale, which is associated with increased risk of stroke in young adults, is twice as common in MA as in nonmigraine controls [12]. In this study, Kurth and colleagues examined whether the association between MA and cardiovascular events in women is modifi ed by the patient’s vascular risk status.

Relation of Dyspnea in Patients Unable to Perform Exercise Stress Testing to Outcome and Myocardial Ischemia

Limited information exists regarding the significance of dyspnea in patients who are unable to exercise and the contribution of myocardial ischemia to this symptom. To assess this, we evaluated results of dobutamine stress echocardiography (DSE) and long-term outcome of patients with dyspnea referred for DSE. We studied 6,376 consecutive patients who were unable to perform an exercise test and were referred for DSE. Patients were classified according to presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac ischemic events (myocardial infarction or revascularization), hospitalization for heart failure (HF), and death. Dobutamine stress echocardiogram was positive for ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate analysis, risk of death was increased in dyspneic patients versus asymptomatic patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR 1.20, p <0.001). Hospitalization for HF occurred more often in patients with dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain), especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain). Risk of cardiac ischemic events in patients with dyspnea was similar versus asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE, dyspnea was associated with a poor outcome. This increased hazard seems not to be linked to myocardial ischemia, but instead to HF and death.

Effect of exercise on platelet activation during aspirin or clopidogrel intake in healthy men

Sudden strenuous exercise increases the risk of ischemic cardiac events in patients with coronary artery disease. The exact mechanism behind this observation is unknown, but platelet activation induced by exercise may be of importance. We hypothesized that brief strenuous exercise would activate platelets in healthy men, assessed by the Platelet Function Analyzer 100 and light transmittance aggregometry. Nearly all participants exhibited increased platelet reactivity after exercise measured by the Platelet Function Analyzer 100, whereas only minor changes were detected by light transmittance aggregometry. A significant increase in plasma von Willebrand Factor was also found in response to exercise. In conclusion, platelet activation occurs during exercise in healthy individuals. This activation is not prevented by use of aspirin or clopidogrel, and may partly be explained by an increase in plasma von Willebrand Factor.

Sodium-Hydrogen Exchange Inhibition by Cariporide to Reduce the Risk of Ischemic Cardiac Events in Patients Undergoing Coronary Artery Bypass Grafting: Results of the EXPEDITION Study

The EXPEDITION study addressed the efficacy and safety of inhibiting the sodium hydrogen exchanger isoform-1 (NHE-1) by cariporide in the prevention of death or myocardial infarction (MI) in patients undergoing coronary artery bypass graft surgery. The premise was that inhibition of NHE-1 limits intracellcular Na accumulation and thereby limits Na/Ca-exchanger-mediated calcium overload to reduce infarct size. High-risk coronary artery bypass graft surgery patients (n = 5,761) were randomly allocated to receive either intravenous cariporide (180 mg in a 1-hour preoperative loading dose, then 40 mg per hour over 24 hours and 20 mg per hour over the subsequent 24 hours) or placebo. The primary composite endpoint of death or MI was assessed at 5 days, and patients were followed for as long as 6 months. At 5 days, the incidence of death or MI was reduced from 20.3% in the placebo group to 16.6% in the treatment group (p = 0.0002). Paradoxically, MI alone declined from 18.9% in the placebo group to 14.4% in the treatment group (p = 0.000005), while mortality alone increased from 1.5% in the placebo group to 2.2% with cariporide (p = 0.02). The increase in mortality was associated with an increase in cerebrovascular events. Unlike the salutary effects that were maintained at 6 months, the difference in mortality at 6 months was not significant. The EXPEDITION study is the first phase III myocardial protection trial in which the primary endpoint was achieved and proof of concept demonstrated. As a result of increased mortality associated with an increase in cerebrovascular events, it is unlikely that cariporide will be used clinically. The findings suggest that sodium hydrogen exchanger isoform-1 inhibition holds promise for a new class of drugs that could significantly reduce myocardial injury associated with ischemia-reperfusion injury.