Levosimendan is superior to enoximone in refractory cardiogenic shock complicating acute myocardial infarction.

OBJECTIVE: Cardiogenic shock is the leading cause of death in patients hospitalized for acute myocardial infarction. The objectives were to investigate the effects of levosimendan, a novel inodilator, compared with the phosphodiesterase-III inhibitor enoximone in refractory cardiogenic shock complicating acute myocardial infarction, on top of current therapy. DESIGN: Prospective, randomized, controlled single-center clinical trial. SETTING: Medical and coronary intensive care unit in a university hospital. PATIENTS: Thirty-two patients with refractory cardiogenic shock for at least 2 hrs requiring additional therapy. INTERVENTIONS: Infusion of either levosimendan (12 microg/kg over 10 min, followed by 0.1 microg/kg/min over 50 min, and of 0.2 microg/kg/min for the next 23 hrs) or enoximone (fractional loading dose of 0.5 mg/kg, followed by 2-10 microg/kg/min continuously) after initiation of current therapy, always including revascularization, intra-aortic balloon pump counterpulsation, and inotropes. MEASUREMENTS AND MAIN RESULTS: Survival rate at 30 days was significantly higher in the levosimendan-treated group (69%, 11 of 16) compared with the enoximone group (37%, 6 of 16, p = 0.023). Invasive hemodynamic parameters during the first 48 hrs were comparable in both groups. Levosimendan induced a trend toward higher cardiac index, cardiac power index, left ventricular stroke work index, and mixed venous oxygen saturation. In addition, lower cumulative values for catecholamines at 72 hrs and for clinical signs of inflammation were seen in the levosimendan-treated patients. Multiple organ failure leading to death occurred exclusively in the enoximone group (4 of 16 patients). CONCLUSIONS: In severe and refractory cardiogenic shock complicating acute myocardial infarction, levosimendan, added to current therapy, may contribute to improved survival compared with enoximone.

Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT).

BACKGROUND: The endothelin (ET-1) system is activated in chronic heart failure (CHF). Whether, what type, and what degree of selective ET blockade is clinically beneficial is unknown. We investigated hemodynamic and neurohumoral effects of 3 weeks of treatment with various dosages of the orally available ET(A) antagonist darusentan in addition to modern standard therapy in patients with CHF. METHODS AND RESULTS: A total of 157 patients with CHF (present or recent NYHA class III of at least 3 months duration), pulmonary capillary wedge pressure > or =12 mm Hg, and a cardiac index < or =2.6 L x min(-1) x m(-2) were randomly assigned to double-blind treatment with placebo or darusentan (30, 100, or 300 mg/d) in addition to standard therapy. Short-term administration of darusentan increased the cardiac index, but this did not reach statistical significance compared with placebo. The increase in cardiac index was significantly more pronounced after 3 weeks of treatment (P<0.0001 versus placebo). Pulmonary capillary wedge pressure, pulmonary arterial pressure, pulmonary vascular resistance, and right atrial pressure remained unchanged. Heart rate, mean artery pressure, and plasma catecholamines remained unaltered, but systemic vascular resistance decreased significantly (P=0.0001). Higher dosages were associated with a trend to more adverse events (including death), particularly early exacerbation of CHF without further benefit on hemodynamics compared with moderate dosages. CONCLUSIONS: This study demonstrates for the first time in a large patient population that 3 weeks of selective ET(A) receptor blockade improves cardiac index in patients with CHF. However, long-term studies are needed to determine whether ET(A) blockade is beneficial in CHF.

Restrictive cardiomyopathy in a patient with primary hyperoxaluria type II.

This is the first report of a cardiac manifestation of a primary hyperoxaluria type II (PH II) with the hemodynamic characteristics of a severe restrictive cardiomyopathy. PH II is a rare inherited metabolic disease characterized by a deficiency of D-glycerate dehydrogenase, which has also glyoxylate reductase activity. This defect causes an accumulation of hydroxypyruvate the precursor of oxalate. The renal excretion of oxalate is impaired causing a deposition of oxalate mainly in the kidneys. To date, less than fifty cases have been reported. Systemic oxalosis in PH II is an occasional finding; thus far, myocardial oxalosis due to PH II has never been reported. Described is the case of a 41 year old male with renal failure and severe neuropathy of unknown cause, who underwent endomyocardial biopsy under the suspicion of cardiac amyloidosis. Echocardiography and cardiac catheterization showed a severe restrictive cardiomyopathy; endomyocardial biopsy established the diagnosis of oxalosis. Plasma oxalate levels were markedly increased, therefore a liver biopsy was performed. Immunoreactivity for D-glycerate dehydrogenase/ glyoxylate reductase was absent and activity of the enzyme was < 5% of normal. In summary, these findings established the diagnosis of a restrictive cardiomyopathy due to PH II.

Perforation of aortic root as secondary complication after implantation of patent foramen ovale occlusion device in a 31-year-old woman.

Transesophageal echocardiography (TEE) revealed a 3-mm-large patent foramen ovale (PFO). No other reason for these neurological events could be found and the patient underwent percutaneous closure of the PFO with a CARDIA Star 03/30 device without periprocedural complications. Four weeks later, the patient underwent a routine control of device without any adverse clinical symptoms. Surprisingly, echocardiography revealed a perforation of the aortic root by an umbrella strut with a small shunt from the aortic root to the right atrium. Magnetic resonance imaging (MRI) confirmed the diagnosis of device malposition. Consecutively, the patient underwent minimal invasive surgery. After removal of the single perforating strut, the bleeding lesion was closed. The patient remained free of any additional complications during the postoperative course and up until now has had uneventful follow-ups.