Arginine vasopressin (AVP) regulation was studied in 42 patients with severe heart failure (CHF) and 10 patients without CHF during cardiac catheterization. Plasma AVP levels were elevated in CHF compared with non-CHF patients (2.98 +/- 2.48 vs. 1.01 +/- 0.44 pg/ml, P less than 0.01). In non-CHF patients, osmotic loading with angiographic contrast caused increases in plasma osmolality (283 +/- 4 to 290 +/- 5 mosmol/l, P less than 0.05) and AVP (1.01 +/- 0.44 to 1.79 +/- 0.20 pg/ml, P less than 0.001). In 10 CHF patients, similar osmotic loading produced an increase in plasma osmolality (275 +/- 13 to 288 +/- 17 mosmol/l, P less than 0.05) and an exaggerated rise in plasma AVP (3.61 +/- 3.17 to 16.30 +/- 12.17 pg/ml, P less than 0.001). The increase in plasma AVP per unit increase in osmolality was greater (P less than 0.01) in the CHF patients (1.36 +/- 1.25 pg . mosmol-1 . 1(-1)) than in non-CHF patients (0.18 +/- 0.17). To determine whether improved cardiac performance would lower AVP levels, 18 CHF patients received the experimental agent MDL 17,043, with improved cardiac index (1.9 +/- 0.4 to 3.3 +/- 0.7 1 . min-1 . m-2, P less than 0.001). Plasma AVP levels did not change significantly (1.99 +/- 0.74 to 2.81 +/- 2.06 pg/ml), but significant inverse correlations were found between changes in plasma AVP and changes in mean (r = -0.53) and systolic (r = -0.65) arterial pressure after MDL 17,043 infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARY MDL 17,043 administered intravenously or orally exerts positive inotropic and vasodilator actions in experimental animal preparations. We studied its acute hemodynamic effects in 15 patients with severe congestive heart failure by right-heart catheterization. Intravenous MDL 17,043 at 10 minutes increased cardiac index (3.4 0.8 vs 1.9 0.4 1/min/m2), narrowed arteriovenous oxygen content difference (4.6 ± 0.8 vs 7.8 2.0 vol%), increased heart rate (98 ± 14 vs 89 ± 18 beats/min), and decreased systemic arterial (67 10 vs 83 ± 11 mm Hg), pulmonary capillary wedge (12 ± 5 vs 24 ± 5 mm Hg) and right atrial (6 ± 5 vs 12 ± 7 mm Hg) mean pressures significantly (p < 0.001). In 11 patients, hemodynamics were monitored hourly for 6 hours. Compared with baseline, the cardiac index and heart rate were higher and mean systemic arterial pressure was lower for 6 hours; pulmonary capillary and right atrial mean pressures were significantly lower for 5 hours. No serious arrhythmias or side effects occurred. These data suggest that MDL 17,043 may be useful for treating congestive heart failure.THE CONCEPT that contractile strength, even of the end-stage myopathic ventricle, can be increased by enhancing the inotropic state of the myocardium has led to the search for a safer, more effective agent than digitalis for treating chronic congestive heart failure. One such prospect is MDL 17,043 fig. 1), which has been shown to possess significant inotropism in animal studies using isolated cardiac muscle strips, normal intact animal preparations, and a model of propranolol-induced heart failure.'-' MDL 17,043 also causes significant peripheral arterial vasodilation in the dog' and is effective both intravenously and orally.' Moreover, acute and chronic therapy with MDL 17,043 in various animal species has shown a remarkable lack of toxicity. For all these reasons, this agent holds hope for more effective oral therapy of heart failure.In this study, we report the acute hemodynamic effects of i.v. MDL 17,043 in 15 patients. Materials and MethodsUsing a protocol approved by the Human Use Committee at our institution, we studied 15 patients with severe congestive heart failure uncontrolled by digitalis and diuretic therapy (table 1). All patients had cardiomegaly (cardiothoracic ratio > 50%) on chest x-ray. The causes of heart failure, documented by cardiac catheterization, were ischemic heart disease in five patients and corrected mitral regurgitation with residual left ventricular dysfunction in two; heart failure was idiopathic in four patients. Of the four remain- ing patients, three (nos. 9, 12 and 14) were in normal sinus rhythm, and radionuclide angiography revealed severe global hypokinesis. Patient 13 was in atrial fibrillation and the ejection fraction by radionuclide angiography was 39%.The average age of the patients was 55 years. There were 11 men and four women. Nine patients had received various vasodilators, but the results were unsatisfactory and the patients were referred for study. In the six other patients, relat...

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MDL 17,043, an agent with both inotropic and vasodilator properties, was evaluated in the treatment of chronic severe heart failure. The early and late hemodynamic, hormonal, pharmacokinetic and clinical responses to oral MDL 17,043 were studied in 20 patients. MDL 17,043 acutely increased cardiac output from 3.6 +/- 0.9 to 4.6 +/- 1.0 liters/min (+28%, p less than 0.001) and decreased mean pulmonary artery wedge pressure from 24 +/- 8 to 13 +/- 8 mm Hg (-46%, p less than 0.001), mean right atrial pressure from 10 +/- 5 to 4 +/- 4 mm Hg (-60%, p less than 0.001) and mean arterial pressure from 78 +/- 9 to 70 +/- 11 mm Hg (-10%, p less than 0.001). Hemodynamic improvement was sustained for 8 hours. Plasma renin activity tended to increase (0.10 less than p greater than 0.05), plasma norepinephrine tended to decrease (0.10 less than p greater than 0.05) and arginine vasopressin did not show any directional change. Elimination half-life for MDL 17,043 was approximately 20 hours. Hemodynamic responsiveness was maintained in six patients undergoing restudy at 4 weeks. Initial subjective improvement in the 20 patients occurred in 90%, was present at 4 weeks in 50% and continued longer than 3 months in 25%. Side effects occurred in 75% and required cessation of treatment in 10%. Thirteen (93%) of 14 patients on long-term therapy died (median time after start of MDL 17,043 therapy 39 days). Deaths were sudden in 69%. It is concluded that oral MDL 17,043 produces early and late hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

L isteria monocytogenes, a foodborne intracellular pathogen, is known to cause infections among neonates, the elderly, immunosuppressed individuals, and pregnant women. This pathogen is a cause of invasive central nervous system involvement such as cerebritis, meningoencephalitis, and abscesses of the spine and brain, and it can cause a flulike syndrome in pregnant patients that can result in fetal infection or death. Very few cases of listerial endocarditis have been reported, and myocardial involvement is almost unheard of. It is unclear how listeria seeds the myocardium, and investigation is necessary to identify particular strains that might exhibit tissue tropism for the myocardium. Strong suspicion and rapid diagnosis of listerial myocarditis are essential to avoiding a fatal outcome.We present an unusual case of listerial myocarditis, note its treatment with antibi otics, and highlight the value of gadoliniumenhanced cardiac magnetic resonance (CMR) in the diagnosis and monitoring of this rare condition. Case ReportIn January 2012, a 47yearold man presented with diaphoresis, progressively wors ening shortness of breath, and generalized weakness, a nonproductive cough, and a lowgrade fever of 4 weeks' duration. He had been unable to get out of bed and called emergency medical services. The responders found him to have a widecomplex, monomorphic ventricular tachycardia (heart rate, 252 beats/min) (Fig. 1A). Immedi ate electrical cardioversion promptly restored sinus rhythm. A 12lead electrocardio gram (ECG) revealed STsegment elevations in leads V 1 and V 2 (Fig. 1B). The patient's cardiac troponin level was mildly elevated at 0.97 ng/mL. Laboratory results included a white blood cell count of 18.4 mm 3 , a normal creatinine kinase level, and normal liver and renal functions. Emergency coronary angiograms revealed no significant stenosis. A left ventricular (LV) angiogram showed hypokinesis of the diaphragmatic and anterobasal segments (estimated ejection fraction, 0.35). After the angiography, the patient's course was stable. A transthoracic echocardiogram (TTE) showed asym metric LV hypertrophy with marked hypertrophy of the basal interventricular septum ( Fig. 2A). Moderate hypokinesis of the basal septum and anterior wall was seen. The TTE findings were consistent with nonobstructive hypertrophic cardiomyopathy.The patient underwent contrastenhanced CMR for further evaluation. The im ages showed a large but poorly defined complex mass compatible with an abscess,