Steven A. Fein

Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: A multicenter study

Milrinone is a new bipyridine inotrope that has shown promise in initial clinical testing when administered intravenously or orally. The present multicenter study was designed to evaluate the clinical effectiveness and safety of sustained (48 hour) intravenous infusions of different doses of milrinone, as would be used clinically, in a controlled fashion using invasive hemodynamic monitoring. Entry was limited to adult patients with chronic heart failure of functional class III or IV, with a cardiac index less than or equal to 2.5 liters/min per m2 or a pulmonary capillary wedge pressure greater than or equal to 15 mm Hg, or both. After stable baseline hemodynamic recordings were obtained, milrinone was given as loading (microgram/kg per 10 min) and maintenance infusions (microgram/kg per min) to 189 patients in one of four loading/maintenance dosage regimens: 37.5/0.375 (low dose, n = 26), 50/0.50 (intermediate dose, n = 95), 75/0.75 (high dose, n = 15) and 50/0.25 (lowest dose, n = 53). The lowest dose was shown to be ineffective for maintenance therapy. Effective individual patient responses were defined as greater than or equal to 20% increase in cardiac index or decrease in pulmonary capillary wedge pressure, or both. During early therapy (less than or equal to 3 hour), 99% of patients showed an effective maximal response, and 90% an effective mean response. An effective mean response was observed during days 1 and 2 in 80% of patients, with a positive dose-response trend (69% response, low dose; 80%, intermediate dose; 93%, high dose; day 1). Each loading regimen was effective, with maximal mean response occurring at 15 minutes. Cardiac index initially increased by an average of 24 to 42% for all patients in the three groups, whereas pulmonary capillary wedge pressure decreased by 24 to 33%. Initial decreases in systemic vascular resistance averaged 15 to 31%. Initial changes in heart rate (+4 to +13%) and mean arterial pressure (-2 to -13%) were modest. Significant mean hemodynamic responses were maintained over the 48 hours. Increases in cardiac index for days 1 and 2 averaged 38 and 39% for those completing constant low dose drug, 34 and 37% for intermediate dose and 73 and 44% for high dose. Decreases in pulmonary capillary wedge pressure for all patients averaged 18 to 32% on days 1 and 2, with little dose response. Heart rate changes were modest and variable, averaging -9 to 9%.(ABSTRACT TRUNCATED AT 400 WORDS)

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine☆

OBJECTIVES The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. BACKGROUND Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. METHODS Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. RESULTS In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. CONCLUSIONS We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.

Myocardial Performance Index Correlates with Right Ventricular Ejection Fraction Measured by Nuclear Ventriculography

Background: Assessment of right ventricular (RV) ejection fraction (EF) by two‐dimensional echocardiography (2D ECHO) is practical but limited because of complex geometry of the RV. Techniques used for accurate measurement of RV EF are invasive or costly. However, derivation of 2D ECHO Doppler parameters to estimate RV function could be useful and inexpensive. Methods: RV EF measured by nuclear ventriculography was compared with 2D ECHO estimates of myocardial performance index (MPI) and peak tricuspid annular systolic velocity (PTASV). Linear regression analysis and sensitivity analysis were used to analyze the data. Results: RV EF measured by nuclear ventriculography correlated with MPI significantly (r =–0.55, P = 0.005) but not with PTASV (r = 0.09, P = 0.69). Using abnormal RV EF <45% measured by nuclear ventriculography, the sensitivity and specificity for MPI > 0.50 were 45.4% and 100%, respectively. The sensitivity and specificity of PTASV ≤ 17.25 cm/sec in detecting abnormal RV EF were 100% and 35.4%. Conclusion: MPI greater than 0.50 indicates that RV function is abnormal and a value of PTASV > 17.25 cm/sec indicates normal RV function.

African Americans With LVH Demonstrate Depressed Sensitivity of the Coronary Microcirculation to Stimulated Relaxation

Abstract—Excess coronary heart disease morbidity and mortality among African Americans remains an important yet unexplained public health problem. We hypothesized that adverse outcome is in part due to intrinsic or acquired abnormalities in coronary endothelial function and vasoreactivity. We compared dose-response curves relating changes in coronary blood flow and epicardial diameter to graded infusions of acetylcholine in 50 African American and 65 white subjects with hypertensive left ventricular hypertrophy (LVH) and normal coronary arteries. These groups were similar for age, body mass index, mean arterial pressure, and indexed left ventricular mass. The same protocol was conducted in 24 normotensive African American and 56 similar white subjects. We found significant depression in the coronary blood flow dose-response curve relation among African Americans when compared with white subjects with similar LVH (P <0.03). Racial differences were observed at all doses of acetylcholine but were less precisely estimated at the highest dose. The same testing among normotensive subjects revealed similar dose-response curves with no significant effect of race. Qualitatively similar results were found with respect to coronary diameter. Adenosine responses, a measure of endothelium-independent function, were similar after partitioning by LVH. Our study demonstrates that there are racial differences in sensitivity of coronary arteries to acetylcholine-stimulated relaxation among those with LVH. These results provide a mechanism whereby racial differences in coronary vasoreactivity might contribute to adverse coronary heart disease outcome among African Americans, a group in whom LVH is prevalent.

β-Adrenergic Blockade and Calcium Channel Blockade in Myocardial Infarction

Because of their hemodynamic and antiarrhythmic actions, beta-adrenergic blockers and calcium-entry blockers have been suggested for use in patients with myocardial infarction (MI) for reducing infarct size, preventing ventricular ectopy, and for prolonging life in survivors of acute MI. Experimental studies have suggested their usefulness in these areas. Clinical studies have demonstrated a role for beta-blockers in the hyperacute phase of MI, and in longterm treatment of infarct survivors. Calcium channel blockers appear to have somewhat less utility in patients with Q wave MIs, but may have an important role in therapy of the non-Q wave infarct.

Home heparin therapy used in a pregnant patient with a mechanical heart valve prosthesis

The optimal anticoagulation therapy for pregnant patients with a mechanical valve prosthesis is uncertain, but teratogenic effects and the high incidence of fetal loss associated with dicumarol derivatives limit the use of these agents as anticoagulants in this setting. A patient with a mechanical valve prosthesis, in the first trimester of pregnancy, stopped taking her warfarin because of personal fears about teratogenicity. Prosthetic valve thrombosis developed, and she required redo mitral valve replacement. Another mechanical prosthesis was inserted without maternal or fetal injury. The patient was maintained on continuous home, intravenous, high-dose heparin therapy for the remainder of her pregnancy. This therapy resulted in a successful pregnancy and delivery without valve thrombosis, hemorrhagic events, or maternal or fetal compromise.

Transesophageal Echocardiographic Diagnosis of Cardiac Rupture

Cardiac rupture is a difficult pre-mortem diagnosis to make and is equally difficult to manage. Transesophageal echocardiography may be useful in expediting the diagnosis and in the management of cardiac rupture related to myocardial infarction.

Effect of Comorbidities and Medications on Left Ventricular Mass Regression After Bariatric Surgery

J Clin Hypertens (Greenwich). 2010;12:223–227. ©2010 Wiley Periodicals, Inc.

Disseminated Intravascular Coagulation with Congestive Heart Failure and Left Ventricular Thrombus: A Case Report with Literature Review of 7 Cases

Patient: Male, 55 Final Diagnosis: Disseminated intravascular coagulation Symptoms: Leg pain • short of breath • swelling legs Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Coagulation abnormalities can accompany acute congestive heart failure (CHF). However, disseminated intravascular coagulation (DIC) is rarely documented in such patients. DIC is characterized by generalized excessive activation of coagulation pathways followed by their depletion with secondary activation of anticoagulation and fibrinolysis. Treatment of the cause is an integral part of management of DIC; thus, recognition of the cause is critical. Case Report: A 55-year-old previously healthy man presented with breathlessness, swelling of both legs, and left leg pain. His physical exam result was consistent with decompensated heart failure. Further testing revealed multiple deep venous thrombi in the upper and lower extremities, arterial occlusion in the left popliteal artery, and an unusual cyst-like left ventricular thrombus. His laboratory evaluation was consistent with severe acute DIC. The patient was managed aggressively with diuretics, transfusions of platelets, and cryoprecipitate and was subsequently anticoagulated. His platelet count and coagulation parameters normalized and coronary angiography did not reveal any obstructive lesions. On day 22, an echocardiogram revealed and MRI confirmed that the intracardiac thrombus had disappeared. He underwent revascularization of the left leg and was successfully discharged from the hospital. Conclusions: Severe biventricular non-ischemic cardiac dysfunction with intra-cardiac thrombi should be considered in patients presenting with DIC. In addition to anticoagulation, treatment of underlying heart failure is critical in such cases.

Factors associated with adverse long-term outcomes in ischemic stroke: development of a prediction model and its validation

We sought to develop and validate the long-term outcomes in ischemic stroke based on demographic, clinical, and echocardiographic variables. Univariable and multivariable logistic regression modeling was performed in 325 consecutive ischemic stroke subjects (initial cohort). Prediction rules were developed and applied in similar 1305 patients (validation cohort). Only age, renal failure, and aortic root sclerosis were associated with increased all-cause mortality on multivariable logistic regression analyses. Based on the hazard ratios, 2 points were given for each decade of age over 40 years old, 6 for renal failure, and 3 for aortic root sclerosis. Long-term mortality was compared between three groups: low risk (0–5 points), moderate risk (6–10 points), and high risk (more than 11 points). In the initial cohort, Kaplan–Meier mean survival estimates were 59·8 ± 1·4 months in low risk and 37·4 ± 3·3 months highrisk groups (P < 0·001). In the validation cohort, Kaplan–Meier mean survival estimates were 53 ± 0·8 months in low risk and 33·1 ± 2·1 months high-risk groups (P < 0·001) (Fig. 1). A high prevalence of stroke along with the heterogeneity in its clinical outcome has generated interest in correctly identifying poor prognostic factors and in the development of prognostic models. Accurate early prediction of long-term prognosis may enable healthcare providers optimize rehabilitation process, secondary prevention care, and potentially improve resource allocation (1). Predictors have been previously identified to have a univariable relationship with the adverse outcome. However when multivariable analysis were employed the relationship of these predictors to the adverse outcomes have not been well established (2). Our study was aimed at developing a simple, accurate prediction model, incorporating only readily available variables, which retained predictive power in a multivariable logistic regression analysis. We conclude that during the index admission, a simple predictive score, which includes age, aortic root sclerosis, and renal function, can easily distinguish the patients with poor prognosis. Prospective validation has confirmed this finding. Acknowledgements