David A. Halon

Usefulness of 64-Slice Cardiac Computed Tomographic Angiography for Diagnosing Acute Coronary Syndromes and Predicting Clinical Outcome in Emergency Department Patients With Chest Pain of Uncertain Origin

Background— Multidetector computed tomography (MDCT) has high diagnostic value for detecting or excluding coronary artery stenosis. We examined performance characteristics of MDCT for diagnosing or excluding an acute coronary syndrome in patients presenting to the emergency department (ED) with possible ischemic chest pain and examined relation to clinical outcome during a 15-month follow-up period. Methods and Results— We prospectively studied 58 patients (56±10 years of age, 36% female) with chest pain possibly ischemic in origin and no new ECG changes or elevated biomarkers. The patients underwent 64-slice contrast-enhanced MDCT, which showed normal coronary vessels (no or trivial atheroma) in 15 patients, nonobstructive plaque in 20 (MDCT-negative patients), and obstructive coronary disease (≥50% luminal narrowing) in 23 (MDCT-positive group). By further investigation (new elevation of cardiac biomarkers, abnormal myocardial perfusion scintigraphy and/or invasive angiography), acute coronary syndrome was diagnosed in 20 of the 23 MDCT-positive patients (ED MDCT sensitivity 100% [20/20], specificity 92% [35/38], positive predictive value 87% [20/23], negative predictive value 100% [35/35]). During a 15-month follow-up period, no deaths or myocardial infarctions occurred in the 35 patients discharged from the ED after initial triage and MDCT findings. One patient underwent late percutaneous coronary intervention (late major adverse cardiovascular events rate, 2.8%). Overall, ED MDCT sensitivity for predicting major adverse cardiovascular events (death, myocardial infarction, or revascularization) during hospitalization and follow-up was 92% (12/13), specificity was 76% (34/45), positive predictive value was 52% (12/23), and negative predictive value was 97% (34/35). Conclusions— We found that 64-slice cardiac MDCT is a potentially valuable diagnostic tool in ED patients with chest pain of uncertain origin, providing early direct noninvasive visualization of coronary anatomy. ED MDCT had high positive predictive value for diagnosing acute coronary syndrome, whereas a negative MDCT study predicted a low rate of major adverse cardiovascular events and favorable outcome during follow-up.

The long-term multicenter observational study of dabigatran treatment in patients with atrial fibrillation (RELY-ABLE) study

Background— During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results— Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE–eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69–1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04–1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80–1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions— During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00808067.

Localization of lesions in the coronary circulation.

The location of coronary artery narrowings in coronary disease (CAD) is of considerable importance in assessing the mass of myocardium at risk as well as patient prognosis. The detailed distribution of coronary lesions was mapped in 302 patients with CAD who had coronary angiography for chest pain. All identifiable coronary lesions were measured manually and the site and degree of narrowing were stored in a computer-based multisegmental model of the coronary tree. A high prevalence of CAD was found in proximal vessels and especially at, or adjacent to, proximal points of branching. In the left anterior descending coronary artery, the lesions were most prevalent immediately after the first diagonal branch and at the origin of this branch. In the right coronary artery, there was a high prevalence of narrowing between the infundibular and acute marginal branches and specifically around the origin of the right ventricular branch. In the left circumflex coronary artery, there was a predilection for narrowing in and around the origin of the first marginal branch. When a ramus intermedius was present, its origin was frequently the site of narrowing.

Predicting late restenosis after coronary angioplasty by very early (12 to 24 h) thallium-201 scintigraphy: Implications with regard to mechanisms of late coronary restenosis

To examine whether late coronary restenosis may be predicted by abnormalities of myocardial perfusion in the early hours after successful percutaneous transluminal coronary angioplasty and to study in greater detail the mechanisms involved in the development of late coronary restenosis after angioplasty, a prospective study was undertaken in 90 consecutive patients. Thallium-201 scintigrams were recorded at rest and during the stress of atrial pacing, 12 to 24 h after angioplasty, and the results were related to the findings at angiography in 70 patients undergoing late cardiac catheterization. A reversible thallium-201 perfusion defect was found in 39 (38%) of 104 myocardial regions supplied by the dilated coronary vessel and identified a subset of patients at high risk of late (6 to 12 months) angiographic restenosis (sensitivity 77%, specificity 67%). In contrast, late coronary restenosis developed in only 7 (11%) of 65 vessels and in 5 (14%) of 37 patients with a nonischemic thallium-201 scintigram on day 1 (p less than 0.005). Multivariate logistic regression analysis of 14 possible preangioplasty and periangioplasty clinical and angiographic variables selected reversible perfusion defect on the thallium-201 scintigram on day 1 (p = 0.016) and immediate postangioplasty residual coronary narrowing (p = 0.004) as significant independent predictors of late restenosis, with younger patient age as an additional less powerful predictor (p less than 0.05). The findings have important implications regarding the pathogenesis of late coronary restenosis in patients undergoing successful angioplasty and they imply that in the majority of these patients pathophysiologic events in the early minutes and hours after angioplasty may determine the development of late restenosis.

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

The use of calcium with verapamil in the management of supraventricular tachyarrhythmias

Verapamil, a calcium channel blocking drug, terminates supraventricular arrhythmias but may have a negative inotropic effect and produce peripheral vasodilatation and hypotension. We studied the efficacy of intravenous calcium gluconate in reversing or preventing the hypotensive effect of verapamil in 31 patients with atrial tachyarrhythmias. In 21 instances, verapamil was given first, and in 13 calcium was used as pretreatment before the administration of verapamil. Calcium gluconate, when given as pretreatment, prevented the fall in blood pressure induced by verapamil, and when given after verapamil restored blood pressure to control values. The administration of calcium did not alter the antiarrhythmic effect of verapamil.

Left ventricular function in β-thalassemia and the effect of multiple transfusions

Left ventricular performance was studied in 23 young patients with severe chronic anemia due to beta-thalassemia major and intermedia. The patients were divided into three groups according to the number of blood transfusions they had received. The left ventricle (LV) was enlarged in patients who had not received blood and larger still in patients who had received multiple transfusions. Echocardiography and systolic time interval measurements showed that systolic function of the LV was good in all the patients and that there was no statistical difference in systolic function in patients who had and those who had not received multiple transfusions. Heart rate was increased in the latter group. Stroke index and cardiac index were high, especially in patients in Group 3. The diastolic closure rate (EF slope) of the anterior mitral leaflet and its amplitude of movement were increased, but less so in Group 3; this may reflect an alteration in diastolic LV distensibility. The results indicate that despite the presence of cardiomegaly and severe clinical congestive heart failure, LV performance is well preserved in patients with beta-thalassemia, even in those who have received repeated blood transfusions. Clinical cardiac failure is the consequence of volume overload and abnormal chamber compliance. There was no evidence in this of a congestive cardiomyopathy.

Identifying patients at high risk for restenosis after percutaneous transluminal coronary angioplasty for unstable angina pectoris

To study the determinants of late restenosis after percutaneous transluminal coronary angioplasty (PTCA) performed in patients with unstable angina pectoris, a prospective study was undertaken in 90 patients. Primary PTCA success was achieved in 84 (93%) patients, dilating 116 of 118 coronary narrowings (1.4/patient), while major complications during PTCA occurred in only 1 patient (1 death). Eighty-two patients (114 dilated arteries) were followed for 25 +/- 11 months: 68 (83%) were in New York Heart Association functional class I or II, 11 (13%) in class III, and there were 3 deaths. Late restenosis was found in 16 (25%) of 65 lesions (29% of 49 patients) studied by angiography 9 +/- 7 months after PTCA. Restenosis was more frequent in left anterior descending coronary artery lesions (p = 0.07) and in those which at the time of PTCA had multiple irregularities (67 vs 14%, odds ratio 12.5, p = 0.002), decreased coronary perfusion (Thrombolysis in Myocardial Infarction grade less than 3) (50 vs 15%, odds ratio 5.7, p = 0.02) or intraluminal thrombus (67 vs 19%, odds ratio 8.7, difference not significant). Multiple irregularities (p = 0.003) and decreased flow (p = 0.02) remained independent predictors of restenosis (goodness of fit 0.88) after adjustment for 12 pre- and peri-PTCA clinical and angiographic variables by logistic regression analysis. These data underline the feasibility of early revascularization by PTCA in patients with unstable angina pectoris. Careful follow-up should be instituted in patients with multiple irregular lesions, decreased coronary perfusion or intraluminal thrombus at the time of PTCA. In such patients, late restenosis may be the rule rather than the exception.

The prevention of cardiac arrhythmias produced in an animal model by the topical application of a phenol preparation in common use for face peeling.

We have shown in an animal model that complex ventricular arrhythmias produced by topical application of a phenol preparation that is used in face peeling can be prevented by a brisk diuresis at the time of application or by gradual application of the phenol preparation. We recommend that continuous cardiac monitoring and recording be performed in patients having topical phenol applications in order to determine the true incidence of cardiac arrhythmias and to ascertain if they are prevented by a forced diuresis, by the gradual application of the preparation, or by a combination of both.

Cardiac computed tomographic angiography for risk stratification and prediction of late cardiovascular outcome events in patients with a chest pain syndrome

BACKGROUND Contrast-enhanced multidetector cardiac computed tomographic angiography (CCTA) has high sensitivity and specificity for diagnosing anatomic coronary stenoses, but its role in predicting late clinical outcome events has not been well studied. METHODS We examined predictive value of CCTA for late major adverse cardiovascular (CV) outcome events (MACE)(CV death, myocardial infarction, myocardial revascularization) (follow-up 18.2+/-6.3, range 9-30 months) in 545 consecutive symptomatic patients (368 (68%) men, 177 (32%) women) with clinical suspicion, but without previously diagnosed, coronary artery disease (CAD) who underwent 40- or 64-channel CCTA. RESULTS MACE occurred in 53/545 (9.7%) patients (early 30 day CCTA-driven events excluded): CV death/myocardial infarction in 3/327 (0.9%) patients with no coronary luminal narrowing >25% (group 1), in 3/127 (2.4%) with >or=1 luminal narrowing(s) of 26-69% (group 2) and in 9/91 (9.9%) with >or=1 coronary luminal narrowing(s) of >or=70% (group 3) (p<0.0001). CV death/myocardial infarction/revascularization occurred in 5/327 (1.5%) group 1 patients, 19/127 (14.9%) group 2 and 29/91 (31.9%) group 3 (p<0.0001). Multivariate analysis (adjusting for age, gender, coronary risk factors and coronary calcium score) identified CCTA stenosis (>25%) as a powerful independent predictor of MACE (HR 10.9, 95%CI 4.1-29.0, p<0.0001). CONCLUSIONS CCTA was useful to predict late clinical outcome events in patients undergoing evaluation of a chest pain syndrome.