Closing the Digitalis Divide: Back to the Basics of Randomized Controlled Trials.

PURPOSE: Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions. METHODS: To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject. RESULTS: The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization. CONCLUSION: As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.

Why Not Dipyridamole: a Review of Current Guidelines and Re-evaluation of Utility in the Modern Era.

Dipyridamole is an old anti-platelet and coronary vasodilator agent that inhibits platelet phosphodiesterase and increases interstitial adenosine levels. Its use in coronary artery disease (CAD) has fallen out of practice in the modern era with the advent of new anti-platelet agents, and most modern guidelines on the management of CAD either neglect to comment on its utility or outright recommend against it. The majority of the studies used in these guidelines are outdated and took place in an era when high doses of aspirin were used and statins were not widely utilized. There is growing evidence in rat models of dipyridamole's synergy with statins through adenosine modulation resulting in significant myocardial protection against ischemia-reperfusion injury and limitation of infract size. The data in human studies are limited but show a similar potential synergy between dipyridamole and statins. It would thus be prudent to reconsider the recommendations against the use of dipyridamole in CAD and to re-evaluate its possible role and potential benefits through well-designed randomized trials combining it with statins, low-dose aspirin, and/or other anti-platelet agents.

Why complicate an important task? An orderly display of the limb leads in the 12-lead electrocardiogram and its implications for recognition of acute coronary syndrome.

BACKGROUND: In the standard ECG display, limb leads are presented in a non-anatomical sequence: I, II, III, aVR, aVL, aVF. The Cabrera system is a display format which instead presents the limb leads in a cranial/left-to-caudal/right sequence, i.e. in an anatomically sequential order. Lead aVR is replaced in the Cabrera display by its inverted version, -aVR, which is presented in its logical place between lead I and lead II. MAIN TEXT: In this debate article possible implications of using the Cabrera display, instead of the standard, non-contiguous lead display, are presented, focusing on its use in patients with possible acute coronary syndrome. The importance of appreciating reciprocal limb-lead ECG changes and the diagnostic and prognostic value of including aVR or lead -aVR in ECG interpretation in acute coronary syndrome is covered. Illustrative cases and ECGs are presented with both the standard and contiguous limb lead display for each ECG. A contiguous lead display is useful when diagnosing acute coronary syndrome in at least 3 ways: 1) when contiguous leads are present adjacent to each other, identification of ST elevation in two contiguous leads is simple; 2) a contiguous lead display facilitates understanding of lead relationships as well as reciprocal changes; 3) it makes the common neglect of lead aVR unlikely. CONLUSIONS: It is logical to display the limb leads in their sequential anatomical order and it may have advantages both in diagnostics and ECG learning.

Resolvin E1 protects the rat heart against reperfusion injury.

The purpose of the present study was to assess whether resolvin E1 (RvE1), an anti-inflammatory mediator derived from eicosapentaenoic acid, would limit myocardial infarct size in the rat. The H9c2 cell line was used to assess whether RvE1 has direct protective effects on cardiomyocytes. In in vivo experiments, Male Sprague-Dawley rats underwent 30 min of ischemia/4 h of reperfusion. Before reperfusion, rats received intravenous RvE1 (0, 0.03, 0.1, or 0.3mg/kg). In in vitro experiments, H9c2 cells were incubated with RvE1 (0, 1, 10, 100, or 1000 nM). Cells were subjected to 18 h of incubation under normoxic conditions, 16 h of hypoxia, or 16 h of hypoxia and 2 h of reoxygenation. In vivo, RvE1 dose dependently reduced infarct size (30.7 +/- 1.7% of the area at risk in the control group and 29.1 +/- 1.6%, 14.7 +/- 1.3%, and 9.0 +/- 0.6% in the 0.03, 0.1, and 0.3 mg/kg groups, respectively, P < 0.001). In vitro, RvE1 increased viability and decreased apoptosis in a dose-dependent fashion in cells exposed to hypoxia or hypoxia/reoxygenation. A maximal effect was achieved at a concentration of 100 nM. RvE1 augmented phosphoinositide 3-kinase activity, attenuated caspase-3 activity, and augmented calcium-dependent nitric oxide synthase activity in cells exposed to hypoxia or hypoxia/reoxygenation. RvE1 increased Akt, ERK1/2, and endothelial nitric oxide synthase phosphorylation and attenuated the levels of activated caspase-3 and phosphorylated p38 levels. AG-1478, an EGF receptor tyrosine kinase inhibitor, blocked the protective effect of RvE1 both in vivo and in vitro and attenuated the RvE1-induced increase in Akt and ERK1/2 phosphorylation. In conclusion, RvE1, an anti-inflammatory mediator derived from eicosapentaenoic acid, has a direct protective effect on cardiomyocytes against ischemia-reperfusion injury and limits infarct size when administered intravenously before reperfusion.

Use of cardiopulmonary pump support during coronary artery bypass grafting in the high-risk: a meta-analysis.

BACKGROUND: Data from randomized trials evaluating the efficacy of on- versus off-pump coronary artery bypass grafting remain inconclusive, particularly in high-risk populations. AIMS: The aim of this study is to compare the outcomes associated with on- versus off-pump coronary artery bypass grafting among high-risk patients. METHODS: We performed a meta-analysis of randomized control trials comparing on- versus off-pump coronary artery bypass grafting, focusing on high-risk populations. Studies focusing on "high-risk" features: European System of Cardiac Operative Risk Evaluation (EuroSCORE) ≥ 5, age > 70 years, preexisting renal insufficiency, history of stroke(s), and the presence of left ventricular dysfunction were included. MEDLINE, Scopus, and Embase were searched for all publications between January 1, 2000 and August 1, 2016, using the following terms: on-pump, off-pump, coronary artery bypass, high-risk, left ventricular dysfunction, elderly, aged, and renal insufficiency. Endpoints included cardiovascular and all-cause mortality, non-fatal myocardial infarction, stroke, need for revascularization, renal failure, and length of hospital stay. RESULTS: Nine studies incorporating 11,374 patients with a mean age of 70 years were selected. There was no statistical difference in cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction, and renal failure between the two groups. There was a decrease in further revascularization at 1 year with on-pump (OR 0.67 (0.50-0.89)). However, there was an increase in length of hospital stay by 2.24 days (p = 0.03) among the on-pump group with no difference in stroke (OR 1.34 (1.00-1.80)). CONCLUSIONS: On-pump is associated with a decreased risk of additional revascularization by 1 year. However, this appears to be a cost of longer hospitalization.

Methylenetetrahydrofolate reductase genotypes and early-onset coronary artery disease.

BACKGROUND: Homozygosity 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. METHODS AND RESULTS: Patients (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. CONCLUSIONS: Homozygosity for the 677C-->T mutation of MTHFR is common and is associated with an increased risk of premature CAD in this population.

Treatment of reinfarction after thrombolytic therapy for acute myocardial infarction: an analysis of outcome and treatment choices in the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (gusto I) and assessment of the safety of a new thrombolytic (assent 2) studies.

BACKGROUND: Early reinfarction after thrombolytic therapy is associated with adverse outcomes and increased mortality. Among patients with reinfarction in the 1992 Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and the 1998 Assessment of the Safety of a New Thrombolytic (ASSENT 2) trials, we investigated temporal and regional differences in the use of repeat thrombolysis, revascularization (angioplasty and/or bypass surgery), or conservative measures and the outcomes of each management strategy. METHODS AND RESULTS: Data from the 4% of patients (n=2301) who experienced reinfarction after thrombolytic therapy were studied. Baseline characteristics, 30-day mortality, and incidence of total and hemorrhagic strokes were compared among the 3 treatment groups. The 30-day mortality did not differ between the repeat thrombolysis and revascularization groups (P=0.72), and it was significantly lower among patients treated by these 2 strategies than in those treated conservatively (11% and 11% versus 28%, respectively; P<0.001). Stroke rates did not differ significantly between the 3 treatment strategies (P=0.49). From 1992 to 1998, the percentage of reinfarction patients treated with repeat thrombolysis decreased from 29.3% to 18.5% in US centers and from 51.4% to 41.9% in all other centers (P<0.001). In contrast, use of revascularization procedures increased from 33.5% to 47.9% in US centers and from 8.1% to 23.0% in all other centers (P<0.001). CONCLUSIONS: Repeat thrombolysis and revascularization are associated with significantly lower mortality among reinfarction patients. Randomized trials are necessary to assess the exact risks and benefits of rethrombolysis versus interventional revascularization in this subset of high-risk patients presenting with reinfarction after thrombolytic therapy.

Noninvasive, transthoracic, low-frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction.

BACKGROUND: Limitations of coronary thrombolysis include the time to reperfusion, patency rate, and bleeding. We evaluated the use of noninvasive transcutaneous ultrasound to augment coronary thrombolysis. METHODS AND RESULTS: In 24 dogs, a thrombotic occlusion of the left anterior descending coronary artery was induced and documented by 12-lead ECG and coronary angiography. After >/=60 minutes of occlusion, tissue-type plasminogen activator (t-PA; 1.42 mg/kg) was given intravenously over 90 minutes. A total of 12 of the 24 dogs had concomitant transcutaneous application of low-frequency ultrasound (27 kHz) over the chest. At 90 minutes, the mean TIMI grade flow in the t-PA alone group was 0.92+/-1.4 compared with 2. 42+/-1.9 in the t-PA plus ultrasound group (P=0.006). TIMI 2 to 3 flow was present in 4 of 12 cases receiving t-PA alone compared with 10 of 12 cases receiving t-PA plus ultrasound (P=0.003). At 180 minutes, mean TIMI grade flow was 0.75+/-1.4 in the t-PA alone group versus 2.58+/-0.9 in the t-PA plus ultrasound group (P=0.001). Pathological examination confirmed the angiographic patency rate and did not reveal injury secondary to ultrasound in the skin, soft tissues, heart, or lungs. CONCLUSIONS: In vivo, the noninvasive transthoracic application of low-frequency ultrasound (1) greatly augments the efficacy of t-PA-mediated thrombolysis, (2) seems safe, and (3) has substantial potential as a noninvasive adjunct to improve coronary patency without increasing the risk of bleeding.

Regional remodeling of atherosclerotic arteries: a major determinant of clinical manifestations of disease.

In this review we present the current data on remodeling, based on in vivo ultrasound imaging or postmortem histologic analysis of native peripheral and coronary arteries from animal models and studies in patients (coronary artery saphenous vein bypass grafts, lesions of restenosis after balloon angioplasty and other catheter-based interventions). Histologic and ultrasound imaging studies of arteries with atherosclerosis and after vascular injury reveal that arterial remodeling is common and that the cross-sectional area of the vessel is not constant. Compensatory enlargement, inadequate compensatory enlargement and shrinkage at the site of atherosclerotic lesions occurs in coronary and peripheral arteries. Current studies demonstrate that arterial remodeling is a major determinant of vessel lumen size.

Prognostic significance of precordial ST segment depression on admission electrocardiogram in patients with inferior wall myocardial infarction.

OBJECTIVES: This study assessed retrospectively the correlation between the pattern of precordial ST segment depression on the admission electrocardiogram (ECG) and hospital mortality in patients with an inferior myocardial infarction treated with intravenous thrombolytic therapy. BACKGROUND: Previous studies have shown that in acute inferior myocardial infarction, ST segment depression in the precordial leads is associated with increased hospital mortality. However, the significance of the different patterns of precordial ST segment depression has been evaluated in only two previous studies. METHODS: The study included 1,321 patients (1,020 men) who enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial in Israel and received intravenous thrombolytic therapy. Patients with an ST segment elevation > or = 0.1 mV in at least two of the inferior leads were included. Patients were classified into four groups on the basis of their admission ECG: group I = patients with no precordial ST segment depression (n = 346); group II = those for whom the sum of ST segment depression in leads V1 to V3 was greater than that in leads V4 to V6 (n = 700); group III = those for whom the sum of ST depression in leads V1 to V3 was equal to that in leads V4 to V6 (n = 162); group IV = those with maximal ST depression in leads V4 to V6 (n = 113). RESULTS: The overall hospital mortality rate was 3.6% (48 patients): for groups I, II, III and IV it was 2.9%, 2.8%, 4.3% and 9.7%, respectively. Multivariable logistic regression analysis confirmed that hospital mortality was independently associated with the pattern of precordial ST segment depression. The odd ratios in group IV relative to group I was 2.78 (95% confidence interval 1.26 to 6.13, p = 0.007). CONCLUSIONS: The risk of mortality is higher in patients with an inferior myocardial infarction and maximal ST segment depression in precordial leads V4 to V6 versus precordial leads V1 to V3 on the admission ECG.

Prognostic significance of the admission electrocardiogram in acute myocardial infarction.

OBJECTIONS: We sought to access the ST segment and the terminal portion of the QRS complex in the initial electrocardiogram (ECG) as tools to predict outcome in patients with acute myocardial infarction given thrombolytic therapy. BACKGROUND: Previous studies assessing early risk stratification of patients with acute myocardial infarction by ECG criteria have focused on the number of leads with ST segment elevation or the absolute magnitude of ST deviation. A new classification independent of the absolute values of ST deviation was pursued. METHODS: Patients with ST elevation and positive T waves in at least two adjacent leads who received thrombolytic therapy were classified into two groups based on the absence (1,232 patients) or presence (1,371 patients) of distortion of the terminal portion of the QRS complex on the admission ECG. RESULTS: There were no differences between groups in the prevalence of previous angina, hypertension, current smoking, anterior infarction, time from onset of symptoms to therapy of type of thrombolytic regimen. Patients with QRS distortion were less likely to have had a previous infarction (12.0% vs. 18.4%, p = 0.02) or diabetes mellitus (16.9% vs. 21.4%, p = 0.003). They had higher peak creatine kinase levels (1,617 +/- 1,670 vs. 1,080 +/- 1,343 IU, p = 0.00001). Hospital mortality for those with and without QRS distortion was 6.8% and 3.8%, respectively (p = 0.0008). Multivariable logistic regression analysis confirmed that hospital mortality was independently associated with distortion of terminal portion of the QRS complex (odds ratio 1.78, 95% confidence interval 1.19 to 2.68, p = 0.004). CONCLUSIONS: Distortion of the terminal portion of the QRS complex on the admission ECG is independently associated with a higher hospital mortality rate in patients with acute myocardial infarction given thrombolytic therapy.

Importance of the conal branch of the right coronary artery in patients with acute anterior wall myocardial infarction: electrocardiographic and angiographic correlation.

OBJECTIVES: This study assessed prospectively the correlation between the conal branch of the right coronary artery and the pattern of ST segment elevation in leads V1 and V3R during anterior wall acute myocardial infarction (AMI). BACKGROUND: The traditional electrocardiographic (ECG) definition of anteroseptal AMI-ST segment elevation in leads V1 to V3-has recently been challenged. The significance of ST segment elevation in lead V1 during anterior wall AMI is unclear. METHODS: The admission 12-lead ECG with additional lead V3R and the coronary angiograms performed within 10 days of hospital admission were evaluated in 28 consecutive patients (mean age +/- SD 62 +/- 9 years) admitted to the coronary care unit with anterior wall AMI. Patients were classified into two groups according to the magnitude of ST segment elevation in lead V1: group A (elevation > or = 1.5 mm, n = 12) and group B (elevation < 1.5 mm, n = 16). Two types of conal branch were identified: small (not reaching the interventricular septum [IVS]) and large (reaching the IVS). RESULTS: ST segment elevation in lead V3R was found in 11 (92%) and 6 (37%) patients from group A and group B, respectively (p < 0.001); a small conal branch was seen in 10 (83%) and 3 (19%) patients, respectively (p < 0.001). Ten patients (all from group B) had a large conal branch. CONCLUSIONS: ST segment elevation in lead V1 in the admission ECG of patients with anterior wall AMI is strongly related to ST segment elevation in lead V3R and is associated with a small conal branch. Our findings suggest that lead V1 reflects the right paraseptal area supplied by the septal branches of the left anterior descending coronary artery (LAD), alone or together with the conal branch. The absence of ST segment elevation in lead V1 during anterior AMI suggests that the IVS is protected by a large conal branch in addition to the septal branches of the LAD (double circulation).

Thrombolysis is an effective and safe therapy in stuck bileaflet mitral valves in the absence of high-risk thrombi.

OBJECTIVES: We sought to evaluate the effectiveness and safety of thrombolytic therapy in stuck mitral bileaflet heart valves in the absence of high-risk thrombi. BACKGROUND: Current recommendations for the thrombolytic treatment of stuck prosthetic mitral valves are partially based on older valve models and inclusion of patients in whom high-risk thrombi were either ignored or not sought for. The feasibility and safety of thrombolysis in bileaflet models may be affected by the predilection of thrombi to catch the leaflet hinge. METHODS: We studied 12 consecutive patients (men/women = 5/7, age 58.8 +/- 14.9 years) who experienced one or more episodes of stuck bileaflet mitral valve over a 33-month period and received thrombolytic therapy with streptokinase, urokinase or tissue-type plasminogen activator. Transesophageal echocardiography was performed in all patients. Patients with mobile or large (>5 mm) thrombi were excluded. Functional class at initial episode was I-II in 4 patients (33.3%) and III-IV in 8 patients (66.6%). RESULTS: Patients receiving thrombolytic therapy achieved an overall 83.3% freedom from a repeat operation or major complications (95% confidence interval 51.6-97.9%). Minor bleeding occurred in three patients (25%) and allergic reaction in one (8.3%). Transient vague neurologic complaints, without subjective findings, occurred in four patients (33.3%). Three patients had one or more relapses within 5.2 +/- 3.1 months from the previous episode, and readministration of thrombolytics was successful. CONCLUSIONS: In clinically stable patients with stuck bileaflet mitral valves and no high-risk thrombi, thrombolysis is highly successful and safe, both in the primary episode and in recurrence. The best thrombolytic regimen is yet to be established.

Persistent ST segment depression in precordial leads V5-V6 after Q-wave anterior wall myocardial infarction is associated with restrictive physiology of the left ventricle.

OBJECTIVES: To examine the relationship between the persistence of ST segment depression in leads V5-V6 after Q-wave anterior wall myocardial infarction (MI) and the filling pattern of the left ventricle (LV). BACKGROUND: Precordial ST segment depression predominantly in leads V5-V6 is associated with increased in-hospital morbidity and mortality after acute myocardial ischemia, perhaps due to reduced diastolic distensibility of the LV. METHODS: We prospectively studied 19 patients after Q-wave anterior wall MI (>6 months). All patients underwent 12-lead ECG recording, symptom-limited treadmill exercise testing with single photon emission computed tomography thallium-201 imaging, transthoracic Doppler echocardiography, cardiac catheterization and measurement of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels. Patients were classified based on the presence of ST segment depression in leads V5-V6: Group I = ST segment depression <0.1 mV (n = 10); Group II = ST segment depression > or =0.1 mV (n = 9). RESULTS: Patients in Group II had greater LV end diastolic pressures (32.4 +/- 6.5 mm Hg vs. 14.8 +/- 6.1 mm Hg; p = 0.0001), higher plasma ANP (44.4 +/- 47.1 pg/ml vs. 10.7 +/- 14 pg/ml; p = 0.04) and BNP levels (89.4 +/- 62.7 pg/ml vs. 23.6 +/- 33.1 pg/ml; p = 0.01), greater left atrium area (20.6 +/- 3.1 cm2 vs. 17.8 +/- 2.4 cm2; p = 0.05), lower peak atrial (A), higher early (E) mitral inflow velocities, a higher E/A ratio and a lower deceleration time (167 +/- 44 ms vs. 220 +/- 40 ms; p = 0.05). Lung thallium uptake during exercise was more common in Group II (78% vs. 10%, p = 0.04). CONCLUSIONS: Persistent ST segment depression in leads V5-V6 in survivors of Q-wave anterior wall MI is associated with increased LV filling pressure and a restrictive LV filling pattern.

The effect of coenzyme Q10 on infarct size in a rabbit model of ischemia/reperfusion.

OBJECTIVE: Coenzyme Q10 has been found to enhance recovery of function after reperfusion in numerous experimental acute ischemia-reperfusion models. We assessed whether coenzyme Q10, administered intravenously either during or 1 h before ischemia, can limit infarct size in the rabbit. METHODS: Anesthetized open-chest rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. In Protocol 1, 12 min after beginning of ischemia rabbits were randomized to intravenous infusion of 30 mg coenzyme Q10 (Eisai Co., Japan) (n = 10) or vehicle (n = 10). In Protocol 2, rabbits were randomized to 30 mg coenzyme Q10 (n = 6) or vehicle (n = 6) treatment 60 min before ischemia. Ischemic zone at risk (IZ) was assessed by blue dye and necrotic zone (NZ) by tetrazolium staining. RESULTS: In both protocols, coenzyme Q10 did not alter heart rate, mean blood pressure, or regional myocardial blood flows in either the ischemic or non-ischemic zones during ischemia or reperfusion. No difference was found in IZ (as fraction of LV weight) (Protocol 1: 0.24 +/- 0.02 vs. 0.25 +/- 0.02; Protocol 2: 0.28 +/- 0.02 vs. 0.28 +/- 0.03, in the control vs. coenzyme Q10 groups, respectively). The NZ/IZ ratio was comparable between the groups in both protocols (Protocol 1: 0.22 +/- 0.04 vs. 0.26 +/- 0.04; Protocol 2: 0.21 +/- 0.06 vs. 0.30 +/- 0.06, in the control vs. coenzyme Q10 groups, respectively). CONCLUSIONS: Coenzyme Q10, administered acutely either during or 60 min before myocardial ischemia, does not attenuate infarct size in the rabbit.

A small animal model of non-ischemic cardiomyopathy and its evaluation by transthoracic echocardiography.

BACKGROUND: Costs for large animal studies have escalated. Therefore there is a need to develop small animal models of non-ischemic cardiac failure and accurate non-invasive techniques that will allow serial quantitation of left ventricular function. OBJECTIVES: The purpose of our study was to determine the efficacy and reliability of adriamycin for inducing cardiomyopathy in rats. We hypothesized that high frequency transthoracic 2-dimensional and M-mode echocardiography would allow for serial testing of cardiac function in this small animal model. METHODS: Adriamycin was administered at a dose of 2.5 mg/kg intravenously once a week for 10 weeks in 54 rats. Transthoracic echocardiography by use of a 7.5 MHz transducer was performed in 19 rats at baseline and additionally at 12 weeks after beginning of adriamycin therapy to measure left ventricular dimensions and calculate fractional shortening. RESULTS: The mortality rate during the treatment period was 11%, but increased to 52% at 13 weeks. Transthoracic echocardiography provided adequate visualization of left ventricular dimensions and cardiac function in a parasternal short axis view. In follow-up echocardiography, pericardial effusion was detected in 8/19 rats (42%). Compared to baseline, end-diastolic diameters increased from 0.56 +/- 0.06 to 0.64 +/- 0.08 mm (p < 0.001), end-systolic diameters increased from 0.27 +/- 0.03 to 0.42 +/- 0.08 mm (p < 0.001), and fractional shortening decreased from 52.8 +/- 4.0 to 34.3 +/- 7.1% (p < 0.001) at 12 weeks. Electron microscopy in a subset of rats revealed cardiomyocyte degeneration, mitochondrial and sarcoplasmatic reticular edema, numerous intracellular vacuoles and 'onion-ring' shaped mitochondrial cristae, characteristic for adriamycin cardiotoxicity in human patients. CONCLUSION: Adriamycin at an intravenous dose of 2.5 mg/kg over 10 weeks can be used to create a reliable model of non-ischemic dilated cardiomyopathy with a high success rate. For in-vivo diagnostic purposes, transthoracic echocardiography provides a reliable technique to non-invasively assess cardiac function quantitatively and qualitatively in follow-up studies in rat cardiomyopathy. This small animal model can easily be used for testing new therapeutic strategies in cardiac failure.

Atherosclerotic cardiovascular mortality during the 1992 riots in Los Angeles.

During the 3-day period of the Los Angeles riots in 1992, there was a significant increase in the total number of deaths investigated by the Coroner's office and deaths attributed to violence and trauma, but not to atherosclerotic cardiovascular mortality. However, there was a significant decrease in cardiovascular mortality in the period following the riots, compared with the period of the riots or the preceding period.

Prognostic significance of maximal precordial ST-segment depression in right (V1 to V3) versus left (V4 to V6) leads in patients with inferior wall acute myocardial infarction.

This study examines whether patients with inferior wall acute myocardial infarction (AMI) and maximal ST-segment depression in left precordial leads are at higher risk for in-hospital mortality. The charts of patients (n = 213) with inferior wall AMI and an initial electrocardiogram that displayed peaked, tall T waves or ST-segment elevation with upright T waves in inferior leads were reviewed, after excluding patients with inverted T waves in inferior leads (n = 75). ST-segment deviation from baseline was measured for all leads. Patients were classified into 3 types: I = no precordial ST-segment depression; II = sum of ST-segment depression in leads V1 to V3 equal to or more than the sum of ST-segment depression in leads V4 to V6; and III = maximal precordial ST-segment depression in leads V4 to V6. Thirty-six patients (17%) died in the hospital. In-hospital mortality rates for patients with types I and II were 12% and 10%, respectively, compared with 41% for those with type III (p < 0.0001). Mortality rates in surviving patients were similar for all types up to 1 year after infarction. Multivariate logistic regression models for in-hospital mortality by ST-segment depression type adjusted for age, previous AMI, diabetes mellitus, and thrombolytic therapy revealed that type III pattern was a strong predictive factor for in-hospital mortality (odds ratio = 4.9, p = 0.0008, 95% confidence interval 1.93 to 12.26). Thus, patients with inferior wall AMI and maximal precordial ST-segment depression in leads V4 to V6 are at high risk for in-hospital mortality.

Clinical significance and predisposing factors to symptomatic bradycardia and hypotension after percutaneous transluminal coronary angioplasty.

Of 180 consecutive patients who underwent uneventful percutaneous transluminal coronary angioplasty (PTCA), 25 (13.9%) had at least 1 episode of symptomatic bradycardia and hypotension during the early postprocedure period. Symptomatic bradycardia and hypotension occurred 1 to 10 hours (mean 4 +/- 2) after PTCA. A higher incidence of symptomatic bradycardia and hypotension was found in patients receiving regular treatment with beta blockers (26% vs 10% in patients without beta blockers in their regimen, p < 0.01), diltiazem or verapamil (20% vs 9%, p < 0.025), or both a beta blocker and diltiazem or verapamil (64% vs 11%, p < 0.001). A higher incidence was also associated with angioplasty of the left anterior descending coronary artery compared with angioplasty of the other coronary arteries (22% vs 8%, p < 0.01). It is concluded that symptomatic bradycardia and hypotension is a common occurrence after PTCA. The incidence is higher after PTCA to the left anterior descending coronary artery and in patients receiving diltiazem, verapamil, and beta-blocking agents; it is particularly high in patients receiving a combination of a beta-blocking agent and either diltiazem or verapamil.

Dissection of the ascending aorta induced by coronary angiography.

We present a 75-year-old woman with an iatrogenic dissection of the ascendin aorta, induced by stenting of the right coronary artery. Coronary angiographic and transesophageal echocardiographic imaging and histology are presented.