Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT).

OBJECTIVES: This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo. BACKGROUND: Ibopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects. Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors, both drugs might be expected to have a favorable long-term effect. METHODS: We studied 161 patients with mild to moderate chronic heart failure (80% in New York Heart Association functional class II and 20% in class III), who were treated with ibopamine (n = 53), digoxin (n = 55) or placebo (n = 53) for 6 months. Background therapy consisted of furosemide (0 to 80 mg); all other drugs for heart failure were excluded. Clinical assessments were made at baseline and after 1, 3 and 6 months. RESULTS: Of the 161 patients, 128 (80%) completed the study. Compared with placebo, digoxin but not ibopamine significantly increased exercise time after 6 months (p = 0.008 by intention to treat analysis). Ibopamine was only effective in patients with relatively preserved left ventricular function, as it significantly increased exercise time in this subgroup (for patients with a left ventricular ejection fraction > 0.30; p = 0.018 vs. placebo). No patient receiving digoxin withdrew from the study because of progression of heart failure, compared with six patients receiving ibopamine and two receiving placebo. At 6 months, plasma norepinephrine was decreased with digoxin and ibopamine therapy (-106 and -13 pg/ml, respectively) but increased with placebo administration (+62 pg/ml) (both p < 0.05 vs. placebo). Plasma aldosterone was unaffected, but renin was decreased by both agents after 6 months (p < 0.05 vs. placebo). Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs. CONCLUSIONS: Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure. However, the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction.

Papillary fibroelastoma of the aortic valve in a patient with an acute myocardial infarction.

We describe a patient with a myocardial infarction in whom a tumor near the aortic valve was identified by routine transthoracic echocardiography. Transesophageal echocardiography proved to be particularly useful in identifying the attachment of the tumor to the aortic valve and enabled a surgical approach through the ascending aorta. On microscopic examination, the tumor appeared to be a papillary fibroelastoma.

Acquired ventricular septal defect and mitral insufficiency without pericardial effusion after stab wound to the chest.

Echocardiography has a role in the management of acute complications of penetrating cardiac trauma. We report the case of a 30-year-old man who sustained a stab wound to the chest. In this case a traumatic perforation of the ventricular septum and the anterior leaflet of the mitral valve caused by a knife occurred without pericardial effusion. The diagnosis was made by transthoracic echocardiography. The ability of transesophageal echocardiography to delineate the intracardiac injuries more precisely helped to guide the surgical procedure.

Nifedipine gastrointestinal therapeutic system versus atenolol in stable angina pectoris. The Netherlands Working Group on Cardiovascular Research (WCN).

The gastrointestinal therapeutic system formulation of nifedipine enables a once-daily dosing resulting in predictable, relatively constant plasma concentrations. To evaluate the efficacy and safety of this formulation and to compare this with the beta-blocker atenolol, we conducted a double-blind, randomised, multi-centre study in 129 male patients with documented exercise induced angina pectoris. After 4 weeks' treatment, nifedipine (60 mg), improved time to onset of 0.1 mV ST-segment depression from 536 s by 72 +/- 117s, time to onset of pain from 619 s by 56 +/- 120 s, and total exercise time from 685 s by 40 +/- 88 s. Atenolol 100 mg, had a comparable effect, time to onset of 0.1 mV ST-segment depression improved from 496 s by 53 +/- 129 s, time to onset of pain from 572 s by 57 +/- 118 s, and total exercise time from 653 s by 33 +/- 99 s. Between group analysis revealed no statistically significant differences for these exercise parameters. Atenolol, but not nifedipine, significantly reduced heart rate and systolic blood pressure at rest and during exercise (P < 0.001 between groups), indicating different modes of action of the drugs. With regard to safety, both drugs were generally well tolerated. There were significantly (P = 0.01) more vasodilation related side effects with nifedipine. These data demonstrate that gastrointestinal therapeutic system formulation of nifedipine and atenolol as once-daily monotherapy are equally effective and safe, but with different effects on exercise parameters.

Echocardiographic diagnosis in carcinoid heart disease.

In this case report the typical echocardiographic features of carcinoid heart disease are presented. Newer treatments such as the use of a somatostatin analogue, interferon and hepatic de-arterialisation have improved the prognosis in patients with carcinoid syndrome. Nevertheless this syndrome portends a poor prognosis in patients with cardiac involvement. Cardiac lesions are mainly located in the right side of the heart. Regurgitation and stenosis of the tricuspid and pulmonary valve, leading to right heart failure, are the most common cardiac manifestations of the disease. Elevated levels of serotonin are probably responsible for the development of these cardiac lesions. Despite treatment resulting in significant reductions of urinary levels of 5-HIAA, regression of the cardiac manifestations in carcinoid syndrome has not been observed. Two-dimensional and Doppler echocardiography are the main tools to establish the diagnosis and severity of carcinoid heart disease. Cardiac surgery for carcinoid heart disease might improve symptoms and longevity, but the scarce data report on early mortality of over 35%.

False aneurysm of the right internal mammary artery.

False aneurysms of the internal mammary artery are extremely rare. A case of false aneurysm of a branch of the right internal mammary artery after median sternotomy is reported. A large right-sided mediastinal mass was seen on the thoracic radiogram. A false aneurysm was suspected on CT-scan and confirmed by angiography. In the same setting percutaneous embolization was performed.

[Atrial septal aneurysm and brain infarct: a causal connection?]. / Atriumseptum-aneurysma en herseninfarct: een causaal verband?

In four patients, 2 women aged 24 and 35 and 2 men aged 37 and 47 years, an ischaemic stroke was observed and an atrial septal aneurysm was found as a possible cardiac source of embolism to the brain. Atrial septal aneurysm is a bulging of the fossa ovalis region, that can be visualised by (preferably transoesophageal) echocardiography. In the four patients there were only few other risk factors for ischaemic stroke (migraine, smoking, oral contraceptives). Cerebral angiography was normal in all cases. Recent literature suggests that a causal relationship exists between atrial septal aneurysm and ischaemic stroke. It is still uncertain what treatment is best.

[Acute right heart failure due to aortic aneurysm: 2 patients with an aortocaval shunt]. / Acute rechtsdecompensatie bij een aneurysma aortae door een links-rechtsshunt.

Two patients, a 72-year-old man and a 34-year-old woman, presented with severe pain in the lower back and abdomen, respectively, accompanied by acute dyspnoea. One patient presented additionally with a palpable pulsatile abdominal mass and a continuous harsh bruit. He subsequently developed massive haemoptysis and went into deep shock. The second patient presented with peripheral cyanosis and a loud systolic heart murmur. She developed increasing respiratory distress and was maximally supported in the intensive care unit. Further investigation revealed acute left-to-right shunting based on rupture of an aortic aneurysm into the venous system in both patients; in the first this was into the V. cava inferior and in the second this was into the right atrium. In both patients, high-output heart failure was present. Acute right heart failure due to a fistula between the aorta and the venous system is a life-threatening and rapidly worsening haemodynamic disturbance. The diagnosis is not difficult but the condition is rare. In some cases, the patient's survival can be achieved by prompt diagnosis followed by operative closure of the fistula.

Left atrial compression caused by hiatus hernia: a rare cause of syncope.

Symptomatic left atrial compression is a rare clinical condition presenting with heart failure, syncope or shock. A Med-line search with the term "left atrial compression" showed only 271 hits. Only 17 cases, of which 11 with hiatus hernia, of left atrial compression due to structures of the gastrointestinal tract were found. We describe a 86-year-old man suffering from repeating syncope due to left atrial compression by a hiatus hernia. This prompted us to review the few cases of atrial compression caused by gastro-intestinal structures.

Transesophageal echocardiography in patients with cryptogenic stroke: does it alter their management? A 3-year retrospective study in a single non-referral centre.

BACKGROUND: Cardiac embolism is estimated to be the aetiology of ischemic cerebral-vascular insults (CVI) in 25% of cases. Transesophageal echocardiography (TEE) is a reliable and widely used examination in the diagnosticwork-up of stroke. TEE is superior to transthoracic echocardiography (TTE) in the search of minor sources of cardiac embolism but it is time consuming and has its inherent risks. AIM: The aim of this study was to determine whether in patients younger than 65 years of age with CVI our TEE-findings would alter their management. Only patients in whom nor the medical record, nor TTE, nor Carotid Ultrasonography could establish an aetiology, were included. METHODS: A 3-year retrospective study was done in patients admitted to the stroke unit of a regional medical centre covering 110,000 inhabitants. The TEE-database was reviewed and all TEE's performed in eligible patients were selected. Minor and major sources of cardiac embolism were listed. The impact of TEE-findings on the management of CVI was evaluated. RESULTS: Fifty-four patients fulfilled the criteria for this study. The mean age was 52 years (range 18 - 65). A major source of cardiac embolism was seen in 6 cases (11.1%). Four patients (7.4%) had infective endocarditis (IE) with vegetations. A small apical thrombosis in a patient with isolated left ventricular non-compaction was noted and in 1 patient dysfunction of a mechanical prosthetic valve was documented. The most frequently encountered minor source of cardiac embolism was a patent foramen ovale (PFO) or small atrial septal defect (ASD) with documented right-to-left shunt during Valsalva manoeuvre (15 patients, 27.8%). Of these 15 patients, an atrial septum aneurysm(ASA) was seen in 7 patients (13%). Our TEE-findings altered the management of CVI substantially in 21 cases (38.9%). The 4 patients with IE and the patient with mechanical valve dysfunction had cardiac surgery. Twelve patients (22.2%) were referred for percutaneous closure of the PFO/ASD. Three patients with PFO/ASD and the patient with IVNC were treated with maintenance therapy of oral anticoagulation. CONCLUSION: In 1 out of 3 patients, younger than 65 years, suffering from CVI in whom nor medical history, nor TTE, nor Carotid Ultrasound could reveal the cause of the CVI our TEE-findings altered their management.

Effects of ibopamine on renal haemodynamics in patients with severe congestive heart failure.

The effects of a single dose of ibopamine on renal haemodynamics, sodium excretion, blood pressure (BP) and heart rate (HR) were investigated in 10 patients (aged 52-82 years) with severe congestive heart failure (CHF) who were in NYHA class IV. All patients used ACE inhibitors, digoxin and diuretics. After determining baseline values, ibopamine 100 mg was administered. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously using radio pharmaceuticals. An increase in GFR and ERPF was observed during 3 and 2 h, with a maximum of 15 and 11%, respectively. The ratio GFR/ERPF representing the filtration fraction (FF) was markedly elevated at baseline, 34%, and remained unchanged. No clinically significant increase of sodium excretion was found. No changes in blood pressure, heart rate, plasma renin activity (PRA) and aldosterone or norepinephrine were observed. We conclude that ibopamine increases both ERPF and GFR in patients with severe CHF, possibly as a consequence of both inotropic cardiac and specific renal effects with equal preglomerular and postglomerular vasodilation. The lack of the presumed fall in FF may be the consequence of the expected DA1-induced renal vasodilation, partially reversed by the alpha adrenergic properties of ibopamine for this dose. Ibopamine caused no clinically significant natriuresis in these salt-depleted patients. No changes in PRA, aldosterone and catecholamines were found.