Aviv Mager

Methylenetetrahydrofolate Reductase Genotypes and Early-Onset Coronary Artery Disease

BACKGROUNDnHomozygosity for the common (677C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with hyperhomocysteinemia, but there is uncertainty as to the association between this mutation and coronary artery disease (CAD). This study examined the association between MTHFR genotypes and age at onset of CAD.nnnMETHODS AND RESULTSnPatients (n=169) with documented myocardial infarction or angiographically documented CAD who were aged < or = 55 years at onset of CAD symptoms and DNA samples from control subjects (n=313) were studied. The prevalence of homozygosity among patients with early CAD onset (aged < or = 45 years) was 28%, which was significantly higher than that in patients with later onset (13%) and in control subjects (14%) (odds ratio 2.4, 95% CI 1.24 to 4.69, P=0.006, and odds ratio 2.7, 95% CI 1.15 to 6.42, P=0.01, respectively). Plasma folate was lower in TT homozygotes who had early CAD onset than in those with later onset (P=0.005). Among patients with plasma folate in the lowest quintile (< or = 12.6 nmol/L), 31% were homozygotes, as were 45% of those with low plasma folate and early CAD onset. There was no difference in the prevalence of traditional risk factors among genotypes. The frequency of homozygosity in patients with < or = 1 risk factor was higher than in those with > or = 2 risk factors (30% versus 12%, P<0.05). In multiple regression analysis, TT homozygosity and plasma folate were independently associated with CAD, but the impact of folate was small.nnnCONCLUSIONSnHomozygosity for the 677C-->T mutation of MTHFR is common and is associated with an increased risk of premature CAD in this population.

Terminal QRS distortion on admission is better than ST-segment measurements in predicting final infarct size and assessing the potential effect of thrombolytic therapy in anterior wall acute myocardial infarction

We assessed predicting final infarct size (using predischarge Selvester score) by 3 electrocardiographic variables in 267 patients with first anterior wall acute myocardial infarction (AMI) undergoing (n = 86) or not undergoing (n = 181) thrombolysis. Patients with previous AMI or inverted T waves in leads with ST elevation were excluded. The sum (sigma) of ST elevation, the number of leads with ST elevation, and the initial electrocardiographic pattern were determined on the admission electrocardiogram (absence (QRS-) or presence (QRS+) of distortion of the terminal portion of the QRS in > or =2 leads (J point > or =0.5 of the R-wave amplitude in leads I, aVL, V4 to V6, or presence of ST elevation without S waves in leads V1 to V3). There was no association between sigmaST elevation and final infarct size in patients who did or did not receive thrombolytic therapy. Analysis of covariance showed that the number of leads with ST elevation (F = 19.6), thrombolysis (F = 25.2), and QRS+ initial pattern (F = 19.5) were all associated with final infarct size (p <0.0001 for all). Among patients who did not receive thrombolytic therapy, the average Selvester score was 19.7+/-9.9 for the QRS- patients and 26.1+/-10.4 for the QRS+ patients (p = 0.02). Among patients who received thrombolytic therapy, the average Selvester score was 11.7+/-9.8 for the QRS- patients and 24.2+/-10.1 for the QRS+ patients (p <0.0001). Thrombolysis reduced final Selvester score only in the QRS- group (p <0.00001), but not in the QRS+ group (p = 0.45). It is concluded that (1) final Selvester score in anterior wall AMI can be predicted by the number of leads with ST elevation, the initial electrocardiographic pattern, and thrombolysis, and (2) thrombolysis reduces final Selvester score only in patients with QRS- pattern.

The ratio of contrast volume to glomerular filtration rate predicts outcomes after percutaneous coronary intervention for ST-segment elevation acute myocardial infarction†

Objective: To assess the value of the ratio between contrast medium volume and glomerular filtration rate (CMGFRr) for prediction of development of contrast‐induced nephropathy (CIN) and mortality in patients with ST‐segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Background: Renal function is a strong predictor of outcome in patients with STEMI. CIN may complicate the course of primary PCI in these patients. Methods: The study population included all 871 consecutive patients with STEMI without cardiogenic shock who underwent primary PCI at our center from January 1, 2001, to October 30, 2006. CIN was defined as an absolute increase in serum creatinine > 0.5 mg/dL or a relative increase >25% within 48 hr after PCI. Results: In‐hospital CIN developed in 72 (8.3%) patients. On linear regression analysis, the following variables were independently associated with CIN: male sex (odds ratio [OR] = 0.42, 95% confidence interval [CI], 0.18–0.97, P = 0.04), GFR < 60 (OR = 3.6, 95% CI, 2.79–4.78, P < 0.0001), multivessel coronary artery disease (OR = 1.67, 95% CI, 1.08–2.58, P = 0.02), CMGFRr (OR = 1.53, 95% CI, 1.01–2.31, P = 0.04, for upper tertile vs. lower two tertiles), and Killip class > 1 (OR = 1.35, 95% CI, 1.03–1.76, P = 0.03). CMGFRr > 3.7 was a strong independent predictor of CIN (OR = 3.87, 95% CI, 1.72–8.68, P = 0.001). Twenty‐six (2.9%) patients died at 1 month after PCI. The following variables were independently predictive of 1‐month mortality: CMGFRr > 3.7 (OR = 3.3, 95% CI, 1.22–9.04, P = 0.018) and multivessel coronary artery disease (OR = 2.3, 95% CI, 1.28–4.07, P = 0.005). Conclusion: The contrast medium‐to‐GFR ratio is a strong predictor of CIN and of 1‐month mortality in patients undergoing primary PCI for STEMI.

Impaired fasting glucose and outcomes of ST-elevation acute coronary syndrome treated with primary percutaneous intervention among patients without previously known diabetes mellitus

BACKGROUNDnFasting blood glucose levels (FG) are related to adverse outcomes in all patients with acute myocardial infarction (AMI), probably more so than admission glucose (AG) levels. We sought to examine this correlation among patients with ST-elevation AMI treated with primary percutaneous coronary interventions (PPCI).nnnMETHODSnOur cohort included 570 consecutive patients without previously known diabetes mellitus who were treated with PPCI for ST-elevation AMI. The cohort was divided according to FG levels measured on days 2 to 4 of hospitalization, while the patients were clinically stable: FG < or = 100 mg/dL, normal range; FG 100-110 mg/dL, mildly impaired FG; FG 110-126 mg/dL, significantly impaired FG; FG > or = 126 mg/dL, diabetic range.nnnRESULTSnOne third of the cohort had impaired FG, of whom 20% had FG levels in the diabetic range. There was a weak correlation between AG and FG levels (r = 0.38, P = .000). In the multivariate analysis, adjusted for AG quartiles, patients with FG > or = 110 mg/dL were more likely to die within 30 days (odds ratio 1.7, 95% CI 1.03-2.70, P = .04). Admission glucose levels did not independently impact on 30-day mortality (odds ratio 0.99, 95% CI 0.50-1.90, P = .96).nnnCONCLUSIONSnFasting blood glucose levels may be routinely assessed among patients with ST-elevation AMI undergoing PPCI, possibly aiding in risk prognostication and the tailoring of therapy.

Use of intravenous morphine for acute decompensated heart failure in patients with and without acute coronary syndromes

Background: Current guidelines regarding the use of intravenous morphine (IM) in the management of patients with acute decompensated heart failure (ADHF) are discordant; whereas the American guidelines reserve IM for terminal patients, the European guidelines recommend its use in the early stage of treatment. Our aim was to determine the impact of IM on outcomes of ADHF patients. Methods: Stepwise logistic regression and propensity score analysis of ADHF patients with and without use of IM was performed in a national heart failure survey. Results: Of the 4102 enrolled patients, we identified 2336 ADHF patients, of whom 218 (9.3%) received IM. IM patients were more likely to have acute coronary syndromes, acute rather than exacerbation of chronic heart failure, and diabetes mellitus and dyslipidemia. They had higher heart rate, were less likely to receive diuretics and more likely to receive aspirin and statins. Unadjusted in-hospital mortality rates were 11.5% versus 5.0% for patients who did or did not receive IM, and the adjusted odds ratio (OR) for in-hospital death was: 2.0 (1.1–3.5, P = 0.02). Using propensity analysis, we identified 218 matched pairs of patients who did or did not receive IM. In multivariable analysis accounting for the propensity score (c-statistic 0.82), IM was not associated with increased in-hospital death (OR: 1.2 (0.6–2.4), P = 0.55). Conclusion: IM was used sparingly in our ADHF cohort, and was independently associated with increased in-hospital death in multivariable analysis, but not in propensity score analysis. Thus, IM may be used in ADHF, but with caution. Further randomized trials are warranted.

Relation between evolutionary ST segment and T-wave direction and electrocardiographic prediction of mycardial infarct size and left ventricular function among patients with anterior wall q-wave acute myocardial infarction who received reperfusion therapy

In the prethrombolytic era it was found that infarct size and left ventricular ejection fraction could be predicted using the Selvester QRS score. We evaluated whether infarct size and left ventricular ejection fraction could be predicted by the predischarge QRS score in patients who had received reperfusion therapy and whether considering the configuration of the ST segments and T waves would increase the accuracy of these predictions. We evaluated 51 patients with first anterior wall myocardial infarction who had received reperfusion therapy and predischarge resting technetium-99m-sestamibi scan. The electrocardiograms recorded on the same day of the scan were analyzed for the QRS score and were divided into 3 groups: A, isoelectric ST and negative T waves; B, ST elevation (> or =0.1 mV) and negative T waves; and C, ST elevation (> or =0.1 mV) and positive T waves. Groups A, B, and C included 12, 23, and 16 patients, respectively. The myocardial perfusion defect extent increased from groups A to C (median 21%, 37%, and 43.5% in groups A, B, and C, respectively; p = 0.023). Similarly, left ventricular ejection fraction decreased (44%, 38%, and 34%, respectively; p = 0.042) from groups A to C. Overall, the correlation between the QRS score and the myocardial perfusion defect extent (rho 0.249; p = 0.08) and ejection fraction (rho -0.229; p = 0.11) was poor. A statistically significant correlation between myocardial perfusion defect size and QRS score was found only in group A (rho 0.599, p = 0.04). Among patients with anterior myocardial infarction who received reperfusion therapy, the predischarge QRS score was predictive of infarct size only in those in whom ST elevation resolved completely. In patients with residual ST elevation there was no correlation between QRS score and infarct size.

Impact of homocysteine-lowering vitamin therapy on long-term outcome of patients with coronary artery disease.

Elevated homocysteine levels are associated with increased risk for mortality in patients with coronary artery disease (CAD). However, the benefit of homocysteine-lowering therapy remains controversial. The aim of this study was to examine the impact of homocysteine-lowering therapy on the long-term outcomes of patients with CAD and its interaction with the methylenetetrahydrofolate reductase genotype. The study sample included 492 patients with early-onset CAD who were genotyped for the C677T mutation in the methylenetetrahydrofolate reductase gene or screened for elevated homocysteine from January 1997 to December 2002. Folic acid > or =400 microg/day with or without additional B vitamins was administered at the attending physicians discretion. There was no difference between treated (n = 140) and untreated patients in age, gender, or prevalence of coronary risk factors. Forty-six patients (9%) died during a median follow-up period of 115 months. Treatment was associated with significantly lower all-cause mortality in patients with homocysteine levels >15 micromol/L (4% vs 32%, p <0.001) but not in patients with lower levels (5% vs 7%, p >0.05). On Cox regression analysis, the following factors were independently associated with all-cause mortality: vitamin therapy (hazard ratio 0.33, 95% confidence interval 0.11 to 0.98, p = 0.046), elevated homocysteine level (hazard ratio 3.5, 95% confidence interval 1.31 to 9.43, p = 0.013), and older age (hazard ratio 1.1, 95% confidence interval 1.04 to 1.14, p <0.0001 for an increment of 5 years). The methylenetetrahydrofolate reductase genotype was not associated with outcomes. In conclusion, long-term folate-based vitamin therapy was independently associated with lower all-cause mortality in patients with CAD and elevated homocysteine levels. This association was not observed in patients with lower homocysteine levels.

Outcome of emergency percutaneous coronary intervention for acute ST-elevation myocardial infarction complicated by cardiac arrest.

BackgroundThe poor prognosis of primary percutaneous coronary intervention (PCI) in patients resuscitated from cardiac arrest complicating acute ST-segment elevation myocardial infarction (STEMI) may at least partly be explained by the common presence of cardiogenic shock. This study examined the impact of emergency primary PCI on outcome in patients with STEMI not complicated by cardiogenic shock who were resuscitated from cardiac arrest. Methods and resultsThe study group included 948 consecutive patients without cardiogenic shock who underwent emergency primary PCI from 2001 to 2006 for STEMI. Twenty-one of them were resuscitated from cardiac arrest before the intervention. Data on background, clinical characteristics, and outcome were prospectively collected. There were no differences between the resuscitated and nonresuscitated patients in age, sex, infarct location, or left ventricular function. The total one-month mortality rate was higher in the resuscitated patients (14.3 vs. 3.4%, P=0.033), but noncardiac mortality accounted for the entire difference (14.3 vs. 1.2%, P=0.001), whereas cardiac mortality was similarly low in the two groups (0 vs. 2.0%, P=NS). Predictors of poor outcome in the resuscitated patients were older age (r=0.47, P=0.032), unwitnessed sudden death (r=0.44, P=0.04), longer interval between onset of cardiac arrest and arrival of a mobile unit (r=0.67, P=0.001) or to spontaneous circulation (r=0.65, P=0.001), low glomerular filtration rate (r=−0.50, P=0.02), and the initial thrombolysis in myocardial infarction grade of flow (r=−0.51, P=0.017). ConclusionEmergency PCI for STEMI not associated with cardiogenic shock exerts a similar effect on cardiac mortality in patients who were resuscitated from cardiac arrest and in those without this complication. The higher all-cause mortality rate among resuscitated patients is explained by noncardiac complications.

Long-term outcome of patients with antiphospholipid syndrome who undergo percutaneous coronary intervention.

Objectives: Patients with antiphospholipid antibody syndrome (APS) have an increased risk of atherothrombotic complications. There are limited data regarding the outcome of patients with APS who undergo percutaneous coronary intervention (PCI). Accordingly, we aimed to assess the long-term outcomes of these patients. Methods: Nineteen APS patients who underwent PCI between the years 2003 and 2008 were compared to 380 patients who had undergone PCI during the same period (PCI group) and were matched by age (±5 years), gender, diabetes and hypertension. In addition, APS patients were compared to 1,458 patients with ST segment elevation myocardial infarction (MI) who were treated with PCI during the same period. Six-month to 4-year clinical outcomes were evaluated. Results: The indication for PCI in the APS group was acute coronary syndrome in 52.6% of patients. After 1 year of follow-up, patients with APS had higher rates of target vessel revascularization than the other two groups, which translated to higher rates of major adverse cardiac events. There were no differences in MI or mortality rates between the groups. Conclusions: Patients with APS who undergo PCI have worse long-term clinical outcomes, driven by higher rates of revascularization, than other patients undergoing PCI. Further study is warranted to examine the mechanisms underlying these findings.

Effect of Narcotic Treatment on Outcomes of Acute Coronary Syndromes

Current guidelines have recommended intravenous narcotics (IVNs) for patients with ST-segment elevation acute coronary syndromes (STEACS) and patients with non-STEACS (NSTEACS), although the safety of IVNs has been challenged. We performed a retrospective analysis of the 30-day outcomes stratified by IVN use among patients enrolled in a national survey, using logistic regression and propensity score analysis. Of the 765 patients with STEACS and 993 patients with NSTEACS, 261 (34.1%) and 97 (9.8%) had received IVNs, respectively. The patients with STEACS who received IVNs were more likely to undergo reperfusion (79.7% vs 55.2%, p <0.0001), received it more rapidly (median 59 minutes vs 70 minutes, p = 0.02), and were more likely to undergo coronary angiography and revascularization. No difference was found in hemodynamic status. The patients with NSTEACS who received IVNs were more likely to present with Killip class II-IV (39.2% vs 10.0%, p <0.001) and to have left ventricular systolic dysfunction (39.0% vs 17.0%, p <0.001). No difference was found in the use of invasive procedures. Using propensity score analysis, of 249 matched STEACS pairs, the rate of 30-day death was lower in the group that had received IVNs (2.4% vs 6.2%, p = 0.04), and this trend persisted after logistic regression analysis (odds ratio 0.40, 95% confidence interval 0.14 to 1.14, p = 0.09). Using propensity score analysis, of 95 matched NSTEACS pairs, no difference was found in the 30-day death rate (2.2% for patients receiving IVNs vs 6.3%, p = 0.16), even after logistic regression analysis (odds ratio 0.56, 95% confidence interval 0.14 to 2.33, p = 0.43). In conclusion, IVNs were commonly used in different scenarios-patients with STEACS were more likely to receive IVNs in the context of prompt reperfusion, and patients with NSTEACS were more likely to receive IVNs in the context of heart failure. In both scenarios, IVN use did not adversely affect the outcomes.