Transition from Intravenous Epoprostenol to Treprostinil Due to Intolerable Side Effects in Patients With Pulmonary Arterial Hypertension.

Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension (PAH); however, it has side effects. Reviewing the side effects associated with epoprostenol and treprostinil is essential for improving the long-term treatment strategies for PAH. This retrospective review included patients with PAH who transitioned from intravenous epoprostenol to intravenous treprostinil owing to intolerable side effects, including high cardiac output symptoms, ascites, and thrombocytopenia. Of the 85 patients who received epoprostenol at our hospital between 2013 and 2021, 16 (11 women), with a median age of 33 (range 26 to 40) years (including 12 with idiopathic PAH, 3 with hereditary PAH, and 1 with connective tissue disease pulmonary hypertension), had to switch from intravenous epoprostenol to treprostinil owing to the side effects. After transitioning, epoprostenol-associated intolerable side effects, such as high cardiac output symptoms, ascites, and thrombocytopenia, were ameliorated. In conclusion, for patients with PAH who have intolerable side effects from epoprostenol and have difficulty in continuing treatment, switching from epoprostenol to treprostinil may be an option. Switching treatment leads to better adherence and improved long-term prostacyclin therapy.

Systemic Artery Vasoconstrictor Therapy in Fontan Patients with High Cardiac Output-Heart Failure: A Single-Center Experience.

Failed Fontan Patients with high cardiac output (CO) heart failure (HF) might have vasodilatory syndrome and markedly high mortality rates. The aim of this study was to review the clinical effects of vasoconstrictor therapy (VCT) for failed Fontan hemodynamics. We retrospectively reviewed 10 consecutive patients with Fontan failure (median age, 33 years) and high CO-HF who had received VCT. The hemodynamics were characterized by high central venous pressure (CVP: median, 16 mm Hg), low systolic blood pressure (median, 83 mm Hg), low systemic vascular resistance (median, 8.8 U·m2), high cardiac index (median, 4.6 L/min/m2), and low arterial oxygen saturation (median, 89%). VCT included intravenous noradrenaline infusion for five unstable patients, oral midodrine administration for nine stable patients, and both for four patients. After VCT introduction with a median interval of 1.7 months, the median systolic blood pressure (102 mm Hg, p = 0.004), arterial oxygen saturation (90%, p = 0.03), and systemic vascular resistance (12.1 U·m2, p = 0.13) increased without significant changes in CVP or cardiac index. After a median follow-up of 21 months, the number of readmissions per year decreased from 4 (1-11) to 1 (0-9) (p = 0.25), and there were no VCT-related complications; however, five patients (50%) developed hepatic encephalopathy, and six patients (60%) eventually died. VCT was safely introduced and could prevent the rapidly deteriorating Fontan hemodynamics. VCT could be an effective therapeutic strategy for failed Fontan patients with high CO-HF.

Preliminary study of the effects of furosemide on blood pressure during late-onset pre-eclampsia in patients with high cardiac output.

OBJECTIVE: To examine the effect of furosemide on hypertension and edema in patients with pre-eclampsia experiencing high cardiac output. METHODS: The present cohort study enrolled patients with pre-eclampsia who were admitted to the pregnancy pathology unit of the Department of Obstetrics and Gynecology, University of Pécs, Hungary, between January 1 and December 31, 2015. Eligible patients had singleton pregnancies with no fetal anomalies, high blood volume, visible edema, and a hematocrit concentration below 37 L/L. Blood pressure was measured and impedance cardiography was used to determine cardiac output for all patients before they received a 40-mg dose of furosemide; after 60 minutes blood pressure and cardiac output were measured again. RESULTS: The study enrolled 14 patients. Lower cardiac output (P=0.002), systolic blood pressure (P=0.002), and diastolic blood pressure (P=0.002) were recorded after furosemide administration, with patient heart rates remaining stable. CONCLUSION: The heart-rate stability suggests that the change of cardiac output was due to a decrease in blood volume. These data suggest that diuretics could be useful in the management of late-onset pre-eclampsia, indicating that an increase in water retention could play a role in the development of late-onset pre-eclampsia.

Vasoplegic syndrome during liver transplantation.

A 56-yr-old woman with chronic hepatitis B and decompensated hepatic cirrhosis was treated with liver transplantation. At the beginning of the neohepatic phase, her arterial blood pressure remained at 60/40 mm Hg for approximately 40 min and did not respond to vasoconstrictive drugs. Her other clinical and laboratory values remained normal, apart from a high cardiac output and low systemic vascular resistance. This patient was diagnosed with vasoplegic syndrome and was treated with i.v. infusion of methylene blue (0.5 mg/kg) and norepinephrine. This report has potential significance to treatment in patients who undergo orthotopic liver transplantation.

Hemodynamically-directed atenolol therapy is associated with a blunted rise in maternal sFLT-1 levels during pregnancy.

OBJECTIVE: Cardiac output and sFlt-1 are elevated prior to clinical evidence of preeclampsia. Early treatment of high cardiac output with atenolol decreases the risk for preeclampsia. We hypothesized that atenolol would impact circulating sFlt-1. METHODS: Cardiac output and plasma sFlt-1 were measured

High output heart failure.

The symptoms and signs of heart failure can occur in the setting of an increased cardiac output and has been termed 'high output heart failure'. An elevated cardiac output with clinical heart failure is associated with several diseases including chronic anaemia, systemic arterio-venous fistulae, sepsis, hypercapnia and hyperthyroidism. The underlying primary physiological problem is of reduced systemic vascular resistance either due to arterio-venous shunting or peripheral vasodilatation. Both scenarios can lead to a fall in systemic arterial blood pressure and neurohormonal activation leading to overt clinical heart failure. In contrast to low output heart failure, clinical trial data in this area are lacking. The use of conventional therapies for heart failure, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and certain beta-blockers with vasodilatory properties, is likely to further reduce systemic vascular resistance resulting in deterioration. The condition, although uncommon, is often associated with a potentially correctable aetiology. In the absence of a remediable cause, therapeutic options are very limited but include dietary restriction of salt and water combined with judicious use of diuretics. Vasodilators and beta-adrenoceptor positive inotropes are not recommended.

Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by mucocutaneous and visceral telangiectasia. Hepatic involvement with vascular malformations may lead to portal hypertension, biliary ischemia, and high-output cardiac failure. Liver transplantation is indicated for life-threatening disease but carries significant risk from surgery and chronic immunosuppression. We report a case of a 47-year-old woman with HHT successfully treated with the vascular endothelial growth factor (VEGF) antibody bevacizumab. The patient was referred for consideration of liver transplantation because of hepatic HHT leading to high-output cardiac failure, diuretic resistant ascites, cholestasis, and malnutrition. As she was considered a high-risk candidate for transplantation, she underwent 6 courses of bevacizumab (5 mg/kg) over 12 weeks. A dramatic improvement in her clinical state was observed after 3 months with reversal of cholestasis, resolution of cardiac failure and ascites, and improvement in nutritional status with a 10% dry weight increase. Treatment induced a marked reduction in liver vascularity and halving of her liver volume from 4807 to 2269 mL over 6 months. This was associated with normalization of her cardiac output from 10.2 to 5.1 L/minute. Correspondingly, she ceased diuretic medications, returned to full-time work, and was delisted as a transplant candidate. She remains well 6 months after completing treatment. In conclusion, antagonism of VEGF receptors led to a dramatic regression of hepatic vascular malformations and reversal of high-output cardiac failure and complications of portal hypertension in this patient with HHT. Bevacizumab may potentially alleviate the need for liver transplantation in this group of patients.

Prenatal diagnosis and therapy of upper extremity vascular malformation causing high cardiac output and Kasabach-Merritt sequence: a report of two cases.

We present two cases of upper extremity vascular malformation causing a high output state in the prenatal period. One fetus responded well to transplacental digitalis treatment. Both newborns had a Kasabach-Meritt sequence including anemia and thrombocytopenia. Postpartum treatment included successful interventional occlusion of the main feeding arteries and subsequent surgical removal of the tumor.

The use of the novel calcium sensitizer levosimendan in critically ill patients.

Levosimendan, a novel calcium sensitizer, enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilation. In this prospective observational study the haemodynamic effects of levosimendan in postoperative critically ill patients are reported. Twelve patients with the need for inotropic support were studied. One dose of levosimendan (12.5 mg) was administered at a rate of 0.1-0.2 microg kg(-1).min(-1), either alone or in addition to pre-existing inotropic therapy. Haemodynamic measurements were obtained at baseline, and at 3 h, 6 h, 12 h, and 24 h after the start of the levosimendan infusion. Levosimendan significantly increased cardiac output from (mean+/-SD) 4.3+/-0.91.min(-1) to 5.2+/-1.51 min(-1) after 24h (P=0.013), by increases in stroke volume (baseline 47+/-15 ml, after 24h 57+/-25 ml, P=0.05), as heart rate remained unchanged. Systemic vascular resistance decreased from 1239+/-430 dyn.sec.cm(-5) at baseline to 963+/-322 dyn.sec. cm(-5) at 24h (P<0.001). Pre-existing inotropic therapy present in ten patients remained unchanged or was reduced. In postoperative critically ill patients, infusion of levosimendan exerted favourable haemodynamic responses. Levosimendan increased cardiac output by increasing stroke volume, which might be attributed primarily to its inotropic properties. Due to its cyclic adenosine monophosphate independent positive inotropic effects, levosimendan may be of value as adjunctive therapy to other inotropic drugs in critically ill patients.

Vasoplegic syndrome after off-pump coronary artery bypass surgery: an unusual complication.

We report the case of a 65-year-old man who developed norepinephrine-resistant vasoplegic syndrome after elective off-pump coronary artery bypass surgery (OPCAB). The failure of norepinephrine to improve the patient's hemodynamics prompted us to start treatment with vasopressin; within 30 minutes, the hemodynamics began to improve. After 12 hours, the patient was stable enough to be weaned from the vasopressin. He was discharged from the hospital on the 10th postoperative day. To our knowledge, ours is the 1st report of vasopressin use for vasodilatory shock after OPCAB in the English-language medical literature. Herein, we discuss the pathophysiology and management of vasoplegic syndrome--which is controversial--with special emphasis on the use of vasopressin in this situation.

[Catastrophic antiphospholipid syndrome and acute heart failure. Report of a case]. / Síndrome antifosfolípido catastrófico y falla cardíaca aguda. Caso clínico.

A 33 years old woman was admitted to the hospital after four days with cough, dyspnea, orthopnea and hemoptysis. Blood pressure was 170/90 mmHg, pulse was 112 and temperature was normal. She had cyanosis and a left ventricular gallop, without heart murmurs. A chest radiograph revealed pulmonary edema and echocardiogram showed a global left ventricular systolic disfunction. Oxygen and furosemide were started, but cardiopulmonary collapse ensued. The patient was supported with mechanical ventilation and treated with inotropic drugs. A right sided cardiac catheterization showed pulmonary wedge pressure of 18 mmHg and a cardiac index of 3 l/min/m2. The levels of creatinine and urea nitrogen were elevated and a urine protein was 97 mg/dl. Coagulation tests were normal except by a positive lupic anticoagulant. Markers of connective tissue diseases or vasculitis were negatives. The clinical evolution suggested that a catastrophic antiphospholipid syndrome was ongoing. Intravenous corticoids, gammaglobulin and cyclophosphamide were administered with transient improvement. On her fourth day of treatment, the patient presented sudden pulmonary bleeding and embolism. A plasmapheresis was performed with improvement of renal, cardiac and pulmonary function. After this episode, the patient has been treated with prednisone and oral anticoagulants treatment for the last two years, without further clinical events.

Síndrome antifosfolípido catastrófico y falla cardíaca aguda. Caso clínico / Catastrophic antiphospholipid syndrome and acute heart failure. Report of a case

A 33 years old woman was admitted to the hospital after four days with cough, dyspnea, orthopnea and hemoptysis. Blood pressure was 170/90 mmHg, pulse was 112 and temperature was normal. She had cyanosis and a left ventricular gallop, without heart murmurs. A chest radiograph revealed pulmonary edema and echocardiogram showed a global left ventricular systolic disfunction. Oxygen and furosemide were started, but cardiopulmonary collapse ensued. The patient was supported with mechanical ventilation and treated with inotropic drugs. A right sided cardiac catheterization showed pulmonary wedge pressure of 18 mmHg and a cardiac index of 3 l/min/m2. The levels of creatinine and urea nitrogen were elevated and a urine protein was 97 mg/dl. Coagulation tests were normal except by a positive lupic anticoagulant. Markers of connective tissue diseases or vasculitis were negatives. The clinical evolution suggested that a catastrophic antiphospholipid syndrome was ongoing. Intravenous corticoids, gammaglobulin and cyclophosphamide were administered with transient improvement. On her fourth day of treatment, the patient presented sudden pulmonary bleeding and embolism. A plasmapheresis was performed with improvement of renal, cardiac and pulmonary function. After this episode, the patient has been treated with prednisone and oral anticoagulants treatment for the last two years, without further clinical events.

[Acute cardiovascular beriberi (shoshin-beriberi)]. / Beriberi cardiovascular agudo (shoshin-beriberi).

Beriberi (BB), thiamine deficiency, has been described in the Asian literature in the 17th century and is characterized by peripheral neuropathy and muscle weakness, also called "dry" beriberi (BB) to differentiate it from "wet" BB, with essentially cardiovascular manifestations. Wet can be either "classic" wet BB in which signs and symptoms of right-sided heart failure with normal or high cardiac output are the presenting features or the "shoshin" BB variant with severe biventricular failure and metabolic acidosis, which must be treated early to prevent the rapid development of low cardiac output failure and sudden death. In this case, we report a 58 year old alcoholic woman who developed dyspnea, oliguria, edema, cardiac failure with high output, metabolic acidosis, renal tubular dysfunction and serum lactate level of 5.6 mEq/L. Neurological examination revealed peripheral neuropathy in the lower legs and cognitive alteration. She was treated with a loading dose of 100 mg of intravenous thyamine and responded with a marked increase in urine output, correction of acidosis, reduction in pulmonary-capillary wedge pressure and a change of the hemodynamic pattern. We conclude that shoshin-BB is uncommonly encountered but not widely recognized. In lactic acidosis and/or hyperdynamic circulation without any other apparent etiology in patients with possible vitamin B1 deficiency, the diagnosis of BB must be considered and thiamine should be administered.

Beriberi cardiovascular agudo (shoshin-beriberi) / Acute cardiovascular beriberi (shoshin-beriberi)

Beriberi (BB), thiamine deficiency, has been described in the Asian literature in the 17th century and is characterized by peripheral neuropathy and muscle weakness, also called "dry" beriberi (BB) to differentiate it from "wet" BB, with essentially cardiovascular manifestations. Wet can be either "classic" wet BB in which signs and symptoms of right-sided heart failure with normal or high cardiac output are the presenting features or the "shoshin" BB variant with severe biventricular failure and metabolic acidosis, which must be treated early to prevent the rapid development of low cardiac output failure and sudden death. In this case, we report a 58 year old alcoholic woman who developed dyspnea, oliguria, edema, cardiac failure with high output, metabolic acidosis, renal tubular dysfunction and serum lactate level of 5.6 mEq/L. Neurological examination revealed peripheral neuropathy in the lower legs and cognitive alteration. She was treated with a loading dose of 100 mg of intravenous thyamine and responded with a marked increase in urine output, correction of acidosis, reduction in pulmonary-capillary wedge pressure and a change of the hemodynamic pattern. We conclude that shoshin-BB is uncommonly encountered but not widely recognized. In lactic acidosis and/or hyperdynamic circulation without any other apparent etiology in patients with possible vitamin B1 deficiency, the diagnosis of BB must be considered and thiamine should be administered (AU)