Diabetes mellitus in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to examine the role of diabetes mellitus in cardiogenic shock (CS) complicating acute myocardial infarction (AMI) in the SHOCK Trial Registry. BACKGROUND: The characteristics, outcomes and optimal treatment of diabetic patients with CS complicating AMI have not been well described. METHODS: Baseline characteristics, clinical and hemodynamic measures, treatment variables, shock etiologies and comorbid conditions were compared for 379 diabetic and 784 nondiabetic patients. Logistic regression was used to examine the association between diabetes and in-hospital mortality, after adjustment for baseline differences. RESULTS: Diabetics were less likely than nondiabetics to undergo thrombolysis (28% vs. 37%; p = 0.002) or attempted revascularization (40% vs. 49%; p = 0.008). The survival benefit for diabetics selected for percutaneous or surgical revascularization (55% vs. 19% without revascularization) was similar to that for nondiabetics (59% vs. 25%). Overall unadjusted in-hospital mortality was significantly higher for diabetics (67% vs. 58%; p = 0.007), but diabetes was only a borderline predictor of mortality after adjustment for baseline and treatment differences (odds ratio for death, 1.36; 95% confidence interval, 1.00 to 1.84; p = 0.051). CONCLUSIONS: Diabetics with CS complicating AMI have a higher-risk profile at baseline, but after adjustment, diabetics have an in-hospital survival rate that is only marginally lower than that of nondiabetics. Diabetics who undergo revascularization derive a survival benefit similar to that of nondiabetics.

Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy. Studies of Left Ventricular Dysfunction.

OBJECTIVES: To assess the relation of left ventricular (LV) and left atrial (LA) dimensions, ejection fraction (EF) and LV mass to subsequent clinical outcome of patients with LV dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry and Trials. BACKGROUND: Data are lacking on the relation of LV mass to prognosis in patients with LV dysfunction and on the interaction of LV mass with other measurements of LV size and function as they relate to clinical outcome. METHODS: A cohort of 1,172 patients enrolled in the SOLVD Trials (n = 577) and Registry (n = 595) had baseline echocardiographic measurements and follow-up for 1 year. RESULTS: After adjusting for age, New York Heart Association (NYHA) functional class, Trial vs. Registry and ischemic etiology, a 1-SD difference in EF was inversely associated with an increased risk of death (risk ratio, 1.62; p = 0.0008) and cardiovascular (CV) hospitalization (risk ratio, 1.59; p = 0.0001). Consequently, the other echo parameters were adjusted for EF in addition to age, NYHA functional class, Trial vs. Registry and ischemic etiology. A 1-SD difference in LV mass was associated with increased risk of death (risk ratio of 1.3, p = 0.012) and CV hospitalization (risk ratio of 1.17, p = 0.018). Similar results were observed with the LA dimension (mortality risk ratio, 1.32; p < 0.02; CV hospitalizations risk ratio, 1.18; p < 0.04). Likewise, LV mass > or =298 g and LA dimension > or =4.17 cm were associated with increased risk of death and CV hospitalization. An end-systolic dimension >5.0 cm was associated with increased mortality only. A protective effect of EF was noted in patients with LV mass > or =298 g (those in the group with EF >35% had lower mortality) but not in the group with LV mass <298 g. CONCLUSIONS: In patients with LV dysfunction enrolled in the SOLVD Registry and Trials, increasing levels of hypertrophy are associated with adverse events. A protective effect of EF was noted in patients with LV mass > or =298 g (those in the group with EF >35% fared better) but not in the group with LV mass <298 g. These data support the development and use of drugs that can inhibit hypertrophy or alter its characteristics.

Mural left atrial thrombus: a hidden danger accompanying cardiac surgery.

OBJECTIVE: To emphasize a potentially lethal condition that is virtually impossible to diagnose preoperatively. DESIGN: Case report with review of the literature. SETTING: University Hospital. PARTICIPANT: The patient requiring urgent surgery for heart failure related to severe aortic stenosis and mild mitral stenosis with poor ventricular function. The patient was elderly and suffered from atrial fibrillation. INTERVENTIONS: Preoperative transesophageal echocardiography followed by mitral valve repair and aortic valve replacement. MEASUREMENTS: Clinical outcome and pathological results. RESULTS: Although preoperative TEE demonstrated no left atrial appendage abnormality. After cardiac manipulation prior to the institution of cardiopulmonary bypass a large left atrial mural thrombus was mobilized from the atrial wall and was free floating in the left atrium. CONCLUSIONS: For high risk patients TEE should be applied intraoperatively to avoid undiagnosed left atrial clot dislodgement.

The utility of dobutamine echocardiography in preoperative evaluation for elective aortic surgery.

BACKGROUND: Preoperative cardiac evaluations have been advocated prior to major vascular procedures to reduce the incidence of postoperative cardiac complications. This study was undertaken to evaluate the efficacy and predictive value of routine dobutamine echocardiography (DE) in the screening of patients undergoing elective aortic surgery. METHODS: Dobutamine echocardiography was performed preoperatively on all patients having elective aortic procedures by our university surgical group from June 1995 to August 1996. The cardiac morbidity and mortality from this group were compared with that of a similar group undergoing elective aortic procedures from June 1993 to May 1995 with no dobutamine echocardiography (NDE). RESULTS: Although there was no statistically significant difference in either overall mortality (4.4% in NDE vs. 2.3% in DE) or cardiac mortality (2.9% in NDE vs. 0% in DE) between the two groups, cardiac events occurred only in those patients with previous coronary artery disease. In addition, dobutamine echocardiography had a negative predictive value of 97% CONCLUSIONS: Although routine screening is not necessary, selective screening of patients using dobutamine stress echocardiography is justified because of its high negative predictive value.

A pharmacokinetic-pharmacodynamic model of d-sotalol Q-Tc prolongation during intravenous administration to healthy subjects.

The objective of this study was to assess the pharmacokinetics and pharmacodynamics of the dextro (d-) isomer of sotalol, a class III antiarrhythmic agent, in healthy young men and women after a single intravenous bolus dose. The design was open-label, randomized, parallel group. Each group (4 men and 4 women) received either 0.5, 1.5, or 3.0 mg/kg d-sotalol as an intravenous infusion for 2 minutes. Serial measurements of the d-sotalol plasma concentration and the Q-Tc interval data were recorded before, during, and for 72 hours after drug administration. The pharmacokinetics of d-sotalol were found to be well described by a three-compartment model with linear elimination clearance from the central compartment. There were no significant differences in the elimination clearance or volume of the central compartment between dose levels or between men and women. However, women were found to have a lower steady-state volume of distribution than men (1.20 L/Kg versus 1.43 L/Kg). The Q-Tc versus d-sotalol plasma concentration data were fitted to a model that assumed a distinct "effect compartment" and sigmoidal Emax response. The baseline Q-Tc, determined from the fittings, was found to be significantly higher in women (0.40 versus 0.38 seconds). The effect compartment clearance was found to be highly variable, with a median of 12.3 (range, 0.2-671,300) L/h. There were statistically significant differences in the effect compartment clearance by dose among men and by gender at a dose of 1.5 mg/kg. There were no significant differences detected between dose groups or genders for the d-sotalol effect site concentration at one half the maximum Q-Tc prolongation from baseline (EC50), EMAX, (the maximum Q-Tc prolongation from baseline) or the Hill coefficient. In conclusion, the pharmacokinetics of d-sotalol after intravenous administration are independent of dose and gender, because the difference between men and women in volume of distribution at steady-state is not clinically significant. The pharmacodynamics of Q-Tc prolongation produced by d-sotalol appear to be independent of dose and gender; however, there is considerable variability in the time course of effects on Q-Tc between individuals.

Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry.

Diabetes is an independent predictor of morbidity and mortality in patients with symptomatic heart failure, patients with asymptomatic left ventricular dysfunction (defined as an ejection fraction of 35% or less), and in a broader registry population with less stringent entry criteria. Although the SOLVD Trials made a major clinical contribution by proving the value of enalapril, diabetes remains a significant predictor of outcome even after adjusting for treatment with enalapril.

Relation of ventricular size and function to heart failure status and ventricular dysrhythmia in patients with severe left ventricular dysfunction.

Patients with severe left ventricular (LV) dysfunction may or may not have overt heart failure and ventricular dysrhythmia. To study factors behind this variability, we examined a subset of 311 patients from the Studies of Left Ventricular Dysfunction-95 with a history of moderate heart failure (treatment trial) and 216 with no failure (prevention trial), all with ejection fractions <0.35. Echocardiographic variables were compared between trials and also correlated with dysrhythmia in 258 patients, and with neurohormones in 199 patients. Compared with prevention patients, treatment patients had larger LV end-diastolic diameter, end-systolic volume, sphericity index, and ratio of early to late diastolic filling velocity by Doppler (E/A ratio), lower LV ejection fraction and atrial contribution to ventricular filling, and similar LV mass, end-diastolic volume, and estimates of systolic wall stress. With prevention and treatment patients combined, the prevalence of abnormally elevated atrial natriuretic peptide was 92% in the highest tertile of E/A ratio compared with 55% in the lower tertiles (p=0.006). Across tertiles of LV end-diastolic volume, there was an increase in the prevalence of nonsustained ventricular tachycardia (24%, 45%, and 45%; p=0.007) and premature ventricular complexes >10/hour (48%, 62%, and 80%; p<0.001). Thus, in severe LV dysfunction, ventricular filling indexes suggestive of high filling pressures, along with larger and more spherical ventricles, are particularly common in patients with overt heart failure, thus suggesting that diastolic properties and the degree of ventricular remodeling affect clinical status. Once ejection fraction is significantly reduced, the prevalence of ventricular dysrhythmia correlates with LV size rather than systolic function. This observation lends support to previous experimental findings on the role of myocardial stretch and scar in the genesis of dysrhythmia.

Traumatic tricuspid regurgitation with cyanosis: diagnosis by transesophageal echocardiography.

This case report demonstrates the utility of transesophageal echocardiography in the rapid diagnosis of cardiac injury from blunt thoracic trauma. Initial transesophageal echocardiography identified a flail tricuspid valve leaflet and regurgitation in a patient with jugular venous distention and hemodynamic instability. Progressive hypoxemia prompted repeat transesophageal echocardiography with contrast enhancement, which revealed opening of the foramen ovale and a right-to-left interatrial shunt. Operative repair of the lesion was lifesaving.

Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: a statewide study. Myocardial Infarction Data Acquisition System Study Group.

We studied the effect of diabetes mellitus (DM) on mortality rate in 42,595 patients in the statewide Myocardial Infarction Data Acquisition System (MIDAS), which included patients with myocardial infarction from 90 nonfederal hospitals in New Jersey during the years 1986 and 1987. Of these patients 9695 (22.8%) had DM. DM was more prevalent among female, black, and older patients. DM was associated with higher mortality rates, both in-hospital (21.5% vs 19.2%, p < 0.001) and during 3-year follow-up (46.7% vs 37.8%, p < 0.001). This relation persisted in both men and women, blacks and whites, and all age groups. DM was an independent predictor of mortality by multivariate Cox proportional hazards regression analysis after adjustments were made for gender, race, age, hypertension, left ventricular dysfunction, chronic pulmonary disease, chronic liver disease, and anemia. This effect of DM was most pronounced in the younger age groups. Relative risk was 1.87 for age group 30 to 49, 1.36 for 50 to 69, and 1.17 for 70 to 89 years (p < 0.0001).

Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy.

BACKGROUND: Studies of Left Ventricular Dysfunction (SOLVD) demonstrated that enalapril therapy significantly improved the clinical course of patients with left ventricular (LV) dysfunction. The goals of this substudy were to evaluate changes in LV structure and function in SOLVD patients and to test the hypothesis that enalapril inhibits remodeling in patients with LV dysfunction. METHODS AND RESULTS: Patients entering both the prevention and treatment arms of SOLVD from 5 of the 23 clinical centers were recruited for this substudy. The 301 patients who participated underwent Doppler-echocardiographic evaluation according to standard protocol before randomization to either enalapril or placebo and again after 4 and 12 months of therapy. Recorded data were analyzed in a blinded fashion at a central core laboratory. Analysis of baseline clinical characteristics showed that patients enrolled in the substudy were generally representative of the SOLVD population, although prevention arm patients were slightly overrepresented in the substudy group (69.8% compared with 61.9% of remaining SOLVD patients). The enalapril group demonstrated significant reductions in the mitral annular E-wave-to-A-wave velocity ratio (due predominantly to a reduction in E-wave velocity), and this response was different from that seen in the placebo group (P = .030). Changes in the E-to-A ratio in the enalapril group correlated significantly with changes in plasma atrial natriuretic peptide (r = .56; P < or = .01). LV end-diastolic and end-systolic volumes increased in placebo but not enalapril-treated patients, and the differences in response between the treatment groups were significant (P = .025 and .019, respectively). LV mass tended to increase in placebo patients and to be reduced in enalapril-treated patients, and the difference in response between the groups was highly significant (P < or = .001). CONCLUSIONS: These data demonstrate that enalapril attenuates progressive increases in LV dilatation and hypertrophy in patients with LV dysfunction. The results support the possibility that the favorable effects of enalapril reported in the SOLVD trials were related to inhibition of LV remodeling.

Nonpharmacologic therapy improves functional and emotional status in congestive heart failure.

PURPOSE: To compare the effects of a multimodal nonpharmacologic intervention to digoxin and to placebo in patients with congestive heart failure receiving background therapy with angiotensin-converting enzyme inhibitors. DESIGN: Randomized, parallel assignment to three treatment groups of 20 patients with congestive heart failure (New York Heart Association Class II and III). INTERVENTION: Nonpharmacologic treatment program included the following: (1) graduated exercise training, three to five times per week; (2) structured cognitive therapy and stress management; and (3) dietary intervention aimed at salt reduction and weight reduction in the overweight. Digoxin was titrated to achieve a blood level between 0.8 and 2.0 ng/ml. Placebo and digoxin were administered in a randomized, double-blind fashion. RESULTS: Echocardiographic ejection fraction improved (p < 0.05) in the digitalis group (change = +4.4 +/- 6.5) compared with both placebo (change = -3.2 +/- 3.9) and nonpharmacologic therapy (change = -3.2 +/- 3.9). The nonpharmacologic treatment program was well tolerated by all patients and resulted in significant improvement (p < 0.05) in exercise tolerance (digoxin = +51 +/- 50 s, placebo = +91 +/- 76, nonpharmacologic therapy = +182 +/- 139), as well as Beck Depression Inventory score (digoxin = +1.2 +/- 4.4, placebo = +2.0 +/- 4.2, nonpharmacologic therapy = -5.0 +/- 4.2), Hamilton Scale scores of anxiety (digoxin = +3.0 +/- 6.8, placebo = +6.0 +/- 2.6, nondrug therapy = -5.2 +/- 5.4), and depression (digoxin = +1.0 +/- 4.9, placebo = +5.0 +/- 5.0, nonpharmacologic therapy = -6.6 +/- 10.1). In addition, weight loss was significantly greater with nonpharmacologic therapy (digoxin = +0.32 +/- 1.76 kg; placebo = -1.35 +/- 1.44 kg; nonpharmacologic therapy = -4.37 +/- 4.50 kg) compared with both digoxin and placebo. CONCLUSIONS: Nonpharmacologic therapy improved functional capacity, body weight, and mood state in patients with congestive heart failure. In contrast, digoxin improved ejection fraction without corresponding changes in exercise tolerance or quality of life.

Differential exercise effects of captopril and nadolol in patients with essential hypertension.

In a crossover study, 12 patients with mild to moderate hypertension were given placebo, captopril (12.5 to 50 mg three times a day), and nadolol (20 to 160 mg once a day) to control the resting diastolic blood pressure to a nearly identical degree (p less than 0.0001) (106.1 +/- 4 placebo, 89.6 +/- 8 captopril, 89.8 +/- 7 nadolol). Both drugs lowered (p less than 0.0004) systolic and diastolic blood pressure at rest and during exercise. However, systolic blood pressure lowering during exercise was more pronounced (p less than 0.05) with nadolol than with captopril (difference of 6 mmHg, 16 mmHg, and 21 mmHg at 5.0, 7.0, and 9.0 metabolic equivalents (METS) respectively). Heart rate was lower (p less than 0.05) at rest and during exercise with nadolol as compared with placebo and with captopril. These data imply different mechanisms of action of the two drugs at rest and during exercise and may help in selection of drug therapy in special patient subsets.

Recurrent nontraumatic aortic tears resulting in valvular avulsion and aortic insufficiency.

A case of aortic insufficiency due to avulsion of two of three semilunar valves was remarkable because of the intimal and medial tears which caused it. The tears were in different stages of repair, suggesting repetitive injury. Antemortem steroid therapy and bouts of violent coughing may explain these unusual findings.

A computerized tube leukocyte adherence inhibition assay in the diagnosis of human lung cancer.

A computerized tube LAI assay was used to determine the antitumor immune response in lung cancer patients. A standardized assay was established by the use of tumor antigen recovered from the spent medium of lung and colon adenocarcinoma cell lines. Furthermore, modulation of the assay by prostaglandin E2 (PGE2) was used to increase its sensitivity. Of 65 patients with epidermoid lung cancer, 34 (52.3%) had a positive nonadherence index (NAI). The NAI was inversely related to tumor burden, with 31 of 44 (70.6%) patients with lung cancer stages I and II and only 3 of 21 (14%.2%) patients with stage III having positive assays (greater than 30%). Addition of PGE2 to the as say increased the overall sensitivity so that a positive NAI was obtained in 88.6% of patients with lung cancer stages I and II, and 88.6% with stage III, respectively. Of 174 individuals from the control group, positive NAI was found in only 9 and 3.8% of patients with chronic obstructive pulmonary disease and normal controls, respectively. These results support previous observations on the specificity and sensitivity of the LAI assay in the diagnosis and study of human cancer.

Failure of the aortic valve to open during inspiration in cardiac tamponade.

A new echocardiographic sign, failure of the aortic valve to open during inspiration, is described in a 35-year-old man with cardiac tamponade. There was disappearance of the radial pulse and blood pressure during inspiration and the usual clinical and echocardiographic signs.