Left ventricular noncompaction cardiomyopathy

Isolated left ventricular noncompaction (ILVNC) is a congenital abnormality in the structure of ventricular tissue due to amorphogenetic defect during embryogenesis. This rare entity can be easily diagnosed by the characteristic appearance of prominent trabeculations and deep inter-trabecular spaces. Clinical manifestations of this disease include benign and malignant ventricular arrhythmia, congestive heart failure signs, cardio-embolic events (stroke), mitral and pulmonary valve incompetence, and reduced global ventricular systolic function. We present the case report of a 58-year-old man with ILVNC.     

Plasma glucose, insulin and free fatty acids in infants with congenital heart disease.

The effect of congestive cardiac failure, hypoxia and hypoglycaemia on glucose tolerance and insulin secretion were studied in selected groups of infants with congenital heart disease. Fasting blood glucose level was significantly decreased in patients with congestive heart failure and in cyanotic infants without congestive heart failure. In the former it seemed to be correlated with the degree of malnutrition, while in cyanotic infants it was independent of the nutritional state. Plasma insulin levels were reduced in infants, with congestive cardiac failure, although their glucose tolerance test and free fatty acid concentrations were normal. It is suggested that the decreased plasma insulin concentration was a consequence of adaptation to reduced requirements. Glucose tolerance and insulin secretion were not affected by hypoxia or hypoglycaemia.     

Dilative cardiomyopathy leading to congestive heart failure in a male squirrel monkey (Saimiri sciureus)

A 17-year-old, 1-kg, colony-housed, male squirrel monkey (Samiri sciureus) developed clinical signs of congestive heart failure. The monkey presented with lethargy, increased heart and respiratory rates, and mild abdominal distention. The clinical history, laboratory analysis, and radiographic findings were consistent with heart failure due to dilative cardiomyopathy. Gross and microscopic examination of the heart confirmed a dilative cardiomyopathy. This is the first report describing congestive heart failure caused by dilative cardiomyopathy in a squirrel monkey. Spontaneous dilative cardiomyopathy may be infrequently observed in the squirrel monkeys because they are not routinely housed in the research environment during their advancing years.     

Congestive cardiomyopathy in the woodchuck, Marmota monax

Congestive cardiomyopathy was diagnosed during post mortem examination in eight of 149 adult woodchucks from New York. The eight woodchucks, four males and four females, died spontaneously without clinical signs of heart failure having been detected. The primary lesion was a grossly enlarged and dilated heart. Histologic lesions consisted of multifocal myocardial degeneration and necrosis. Secondary lesions of congestive heart failure were observed.     

Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure

In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.     

The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome

Anemia is a major problem in patients with chronic kidney insufficiency. The development of recombinant human erythropoietin has enabled physicians to correct this anemia. Although anemia has not been considered to be a common or important contributor to congestive heart failure, anemia of any cause can lead to cardiac damage and eventually congestive heart failure. Our joint renal-cardiac heart failure team found that anemia was indeed very common in congestive heart failure and was associated with severe, medication-resistant cardiac failure. Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized. Subsequent investigations by others have confirmed many of our observations. We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome. Treatment of the anemia in congestive heart failure may prove vital in preventing progression of both the heart failure and the associated renal disease.     

Tangential triangular resection: an option to treat the giant left atrium

A 21-year-old woman presented with congestive heart failure caused by congenital mitral and tricuspid insufficiency, associated with great left atrium enlargement. Transthoracic echocardiogram revealed heart dextroversion associated with mitral and tricuspid severe insufficiency and left atrium enlargement (14 cm), confirmed by magnetic resonance study. The left atrium was reduced by a tangential triangular resection of the posterior wall, between the pulmonary veins, suturing the edges of the left atrium with bovine pericardium strip reinforcement. Mitral and tricuspid valves were repaired. The postoperative course was uneventful, and the patient was discharged in the 15th postoperative day. A control magnetic resonance study revealed a 50% reduction in left atrium size. Evolution of left atrium resection is excellent, with low recurrence of arrhythmias, embolism, or heart failure.     

Localization of the insulin-like growth factor system in a rat model of heart failure induced by myocardial infarction.

Although cardiac effects of growth hormone (GH) and insulin-like growth factor (IGF)-I have been reported in experimental models of heart failure and in human dilated cardiomyopathy, the IGF system has not been comprehensively assessed in the failing heart. We therefore localized the IGF system in the left ventricle during congestive heart failure after myocardial infarction (MI) in the rat. The left anterior descending coronary artery was ligated in adult female Sprague-Dawley rats and hearts were examined after 6 months when congestive heart failure had developed. In situ hybridization histochemistry was used to localize mRNA for the components of the IGF system in the left ventricle of sham and congestive heart failure animals. We were able to detect changes in the spatial distribution of mRNA for IGF-I and IGF binding proteins 3, 4, 5, and 6 in the left ventricle during congestive heart failure after MI. IGF-I and the binding proteins were predominantly increased in the infarct/peri-infarct area of the left ventricle. Other components of the IGF system were indistinguishable from the low to undetectable levels in sham-operated rats. These results demonstrate that the IGF system is altered in the failing heart and suggest that the IGF system plays an important role in the response of the heart to MI and consequent failure.     

SURGICAL MANAGEMENT OF A NEONATE WITH INTERRUPTED AORTIC ARCH, TRANSPOSITION OF THE GREAT ARTERIES, AND TRICUSPID ATRESIA

A critically ill infant presented to our Center with congestive heart failure due to Type A interrupted aortic arch, D-transposition of the great arteries, tricuspid atresia, a large ventricular septal defect, and a closing ductus arteriosus. Partially corrective surgery including aortic arch reconstruction, ductal division, and pulmonary artery banding was successful. Future total correction is planned.     

The value of (NT-pro) BNP in the diagnosis,prognosis and treatment of congestive heart failure

Congestive heart failure constitutes one of the major causes of morbidity and mortality in Western countries. However, it is often misdiagnosed and the validity of the diagnosis is often difficult to establish. The clinical signs are not very sensitive and symptoms are nonspecific. Secretion of natriuretic peptides is increased in situations of cardiac overload. Testing the levels of these peptides, especially BNP and NT-proBNP, appears to offer a significant advance in the diagnosis and treatment of heart failure. In this article we would like to discuss the value of natriuretic peptides in congestive heart failure and give a short review of the literature.     

The diurnal rhythm of plasma aldosterone and plasma renin activity in patients with congestive heart failure

Study on a diurnal rhythm of plasma aldosterone (PA) and plasma renin activity (PRA) was performed in 8 patients with congestive heart failure. All patients had been digitalized and received diuretics under mild sodium restriction. An obvious diurnal rhythm of PA similar to the normal subjects, with the lowest value in the evening and the highest value in the morning, was observed in 7 of 8 cases, while a diurnal rhythm of PRA was obscure except in one case. The PA generally did not run parallel with PRA. Although the reason of the absence of PRA diurnal rhythm in congestive heart failure was not clear, it was considered that reninangiotensin system did not play a significant role for the development of PA diurnal rhythm in congestive heart failure. The determined PA values were entirely within normal range except in 2 cases, although they were administered the potent diuretics chronically. A high PA value was observed only in early morning in one case, while all determined PA values were extremely high in another case with severe congestive heart failure involved in cardiac liver cirrhosis. The PRA values were relatively low in 2 cases, normal in 5 and high in one.     

Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring

Patent arterial duct (PAD) is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area) is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of pulmonary overcirculation secondary to a left-to-right shunt must be excluded. Coronary, systemic and pulmonary arteriovenous fistula, peripheral pulmonary stenosis and ventricular septal defect with aortic regurgitation and collateral vessels must be differentiated from PAD on echocardiogram. In preterm infants with symptomatic heart failure secondary to PAD, treatment may be achieved by surgical ligation or with medical therapy blocking prostaglandin synthesis (indomethacin or ibuprofen). Transcatheter closure of the duct is usually indicated in older children. PAD in preterm and low birth weight infants is associated with significant co-morbidity and mortality due to haemodynamic instability. Asymptomatic patients with a small duct have a normal vital prognosis but have a lifetime risk of endocarditis. Patients with moderate-to-large ducts with significant haemodynamic alterations may develop irreversible changes to pulmonary vascularity and pulmonary hypertension.     

Dilated Cardiomyopathy with Increased SR Ca2+ Loading Preceded by a Hypercontractile State and Diastolic Failure in the α1CTG Mouse

Mice over-expressing the α₁₋subunit (pore) of the L-type Ca²⁺ channel (α_1CTG) by 4months (mo) of age exhibit an enlarged heart, hypertrophied myocytes, increased Ca²⁺ current and Ca²⁺ transient amplitude, but a normal SR Ca²⁺ load. With advancing age (8–11 mo), some mice demonstrate advanced hypertrophy but are not in congestive heart failure (NFTG), while others evolve to frank dilated congestive heart failure (FTG). We demonstrate that older NFTG myocytes exhibit a hypercontractile state over a wide range of stimulation frequencies, but maintain a normal SR Ca²⁺ load compared to age matched non-transgenic (NTG) myocytes. However, at high stimulation rates (2–4 Hz) signs of diastolic contractile failure appear in NFTG cells. The evolution of frank congestive failure in FTG is accompanied by a further increase in heart mass and myocyte size, and phospholamban and ryanodine receptor protein levels and phosphorylation become reduced. In FTG, the SR Ca²⁺ load increases and Ca²⁺ release following excitation, increases further. An enhanced NCX function in FTG, as reflected by an accelerated relaxation of the caffeine-induced Ca²⁺ transient, is insufficient to maintain a normal diastolic Ca²⁺ during high rates of stimulation. Although a high SR Ca²⁺ release following excitation is maintained, the hypercontractile state is not maintained at high rates of stimulation, and signs of both systolic and diastolic contractile failure appear. Thus, the dilated cardiomyopathy that evolves in this mouse model exhibits signs of both systolic and diastolic failure, but not a deficient SR Ca²⁺ loading or release, as occurs in some other cardiomyopathic models.     

Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis

Data from population- and clinic-based epidemiologic studies of rheumatoid arthritis patients suggest that individuals with rheumatoid arthritis are at risk for developing clinically evident congestive heart failure. Many established risk factors for congestive heart failure are over-represented in rheumatoid arthritis and likely account for some of the increased risk observed. In particular, data from animal models of cytokine-induced congestive heart failure have implicated the same inflammatory cytokines produced in abundance by rheumatoid synovium as the driving force behind maladaptive processes in the myocardium leading to congestive heart failure. At present, however, the direct effects of inflammatory cytokines (and rheumatoid arthritis therapies) on the myocardia of rheumatoid arthritis patients are incompletely understood.     

Elevation of taurine in human congestive heart failure

The concentration of taurine in the left ventricle of the heart was doubled in patients who had died of chronic congestive heart failure compared to patients who had died of other causes and had no cardiac pathology. In the absence of congestive heart failure, a similar elevation in taurine level was seen in patients with high blood pressure compared to patients with lower blood pressures. The levels of taurine in heart failure were not affected by digitalis treatment. The concentration of taurine in the aorta was almost the same in patients who had died of congestive heart failure and patients who had died of other causes, suggesting that the increase in concentration of taurine might be specific to the heart.     

Elevated plasma vasopressin in cardiomyopathic hamsters

Hamsters of the BIO 14.6 strain characteristically develop cardiomyopathy as they age, and hamsters of this strain have overt signs of heart failure by 11 months of age. Plasma levels of the posterior pituitary hormone arginine-vasopressin (AVP) were found to be elevated (approximately 2-fold) in 11 month old BIO 14.6 hamsters, compared to age-matched hamsters of a control strain. AVP appeared inappropriately elevated in these animals, since they were neither hyperosmotic nor markedly hypotensive. The elevated levels of AVP observed in these animals appears to contribute to vasomotor tone, since intravenous adminstration of a specific antagonist of the vasoconstrictor action of AVP [d(CH₂)₅Ome(TYR)AVP] elicited a fall in arterial pressure (9±2 mm Hg, n=6, p<0.05). The AVP antagonist had no effect on arterial pressure in hamsters of a control strain, and vehicle administration had no effect on arterial pressure in either strain. These data indicate that inappropriately elevated levels of AVP contribute to the cardiovascular state of myopathic hamsters. Since elevated plasma AVP has been noted in human congestive heart failure, these results suggest that AVP may contribute to the cardiovascular status during congestive heart failure.     

Alpha 1-adrenoceptor activity in arterial smooth muscle following congestive heart failure

The interactions between yohimbine (selective alpha 2-antagonist) with noradrenaline (mixed agonist) and phenylephrine (selective alpha 1-agonist) were studied in the canine dorsal pedal artery in an attempt to characterize the peripheral vascular response to adrenergic agents before and after the development of congestive heart failure in the dog. The contractile responses of the dorsal pedal artery to potassium chloride were also examined. Both noradrenaline and phenylephrine contracted the dorsal pedal artery in a concentration-dependent manner before and at peak heart failure, the responses to the agonists being enhanced at heart failure. The responses of the artery to potassium were not modified by congestive heart failure. Yohimbine caused concentration-dependent antagonism of noradrenaline, without altering the magnitude of the maximum response, providing pA2 values ranging from 8.26 to 7.06 against low and high concentrations of noradrenaline, respectively, before heart failure development. Following heart failure, the pA2 values for yohimbine against noradrenaline remained unchanged, but slopes from the Arunlakshana-Schild plots were significantly different from unity, implying a noncompetitive antagonism. The pA2 values of yohimbine against phenylephrine were at least 10 orders of magnitude lower than those against noradrenaline. After congestive heart failure, yohimbine was even less effective against high concentrations of phenylephrine. These findings suggest that enhanced vasoconstriction during heart failure results, in part, from increased alpha 1-adrenoceptor mechanisms in peripheral arterial smooth muscle.     

Increased gene expression of plasminogen activators and inhibitors in left ventricular hypertrophy

In the early stages of left ventricular hypertrophy (LVH) acute adaptive changes occur in the coronary vasculature as it remodels. Plasminogen activators (PAs) and inhibitors (PAIs) have the potential effects of proteolytic degradation that is relevant to tissue remodeling and angiogenesis. Our study focused on the possible roles of PAI-1, PAI-2, uPA and tPA in myocyte hypertrophy and angiogenesis in the early and late stages of pressure overload induced left ventricular hypertrophy (LVH). We divided seventeen adult swine, weighing 24.2 ± 6.5 kg, into four groups: control, sham-operated, early LVH and late heart failure LVH group. At surgery we placed a fixed constrictor on the ascending aorta immediately above the aortic valve. This increased LV systolic pressure from 133 ± 15 to 193 ± 24 mm Hg after the surgery. We subdivided the early group into groups of 3 animals each that we euthanized at 8, 24 and 72 h after operation and obtained heart samples for analysis. In the late heart failure group individual animals were euthanized at 55, 59, 62 and 72 days after the detection of congestive heart failure. We also obtained tissue samples from the control and sham-operated swine. Sections for histologic analysis were fixed in 10% buffered formalin. We isolated RNA, size fractionated it using 1% formaldehyde-agarose gel electrophoresis and then did Northern blots. The mRNAs from both PAI-1 and PAI-2 showed a remarkable increase at 8 and 24 h after acute aortic constriction and returned to control by 72 h. Regional differences showed that most of the increases were in the endocardium. Three animals in the late heart failure LVH group were determined to be in congestive heart failure at about 2 months after the onset of aortic constriction. In these animals PAI-1 and PAI-2 were increased in both the left and right ventricles but remained low in an animal of the same elevation in aortic pressure seen by the LV who did not have congestive failure. These data suggest that PA and PAI gene expressions change before morphologic changes occur in the early stages of developing LVH. Also at the time of onset of congestive heart failure this increased expression reappears. PAs and PA inhibitors mRNA levels vary in the different regions of the heart reflecting changing wall stresses. Thus, the PAs and PA inhibitors may play an important role in angiogenesis that occurs during the early stages of LVH. The increased expression in the late stage of LVH may reflect further changes in wall stresses since these animals also showed overt clinical signs of heart failure.     

Tracheotomy in a case of tracheobronchitis secondary to influenza

Five to 10 per cent of cretinism in the United States is due to some congenital enzymatic defect in thyroid hormone synthesis. The clinical signs of hypothyroidism appear in early infancy. Differentiation from athyreotic cretinism is important because the metabolic defect tends to be familial and its presence in the patient's infant relatives should be diagnosed as early as possible. The differentiation is easily made if a goiter is discernible, but if it is not, radioiodine uptake should be measured, for in this condition the uptake is normal or greater. Thyroid replacement is the treatment in either the athyreotic state or the metabolic deficiency. The three known defects in thyroid hormone synthesis are (1) failure to oxidize iodine to elemental iodine resulting in failure of all subsequent processes; (2) failure to deiodinate free iodotyrosine, and (3) failure to form iodothyronine although the previous steps are accomplished.