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Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction < or = 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by approximately 6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an approximately 2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack of timely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the "buy-and-bill" process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice., (© 2024. The Author(s).)

A 33-year-old man presented with acute nontraumatic cardiac tamponade as a result of pneumococcal pericarditis in association with pneumococcal pneumonia. Hypotension, tachycardia and pulsus paradoxicus, 50 mm Hg, were present. Echocardiographic findings were compatible with cardiac tamponade. Pericardiocentesis was performed. Acute nontraumatic pericardial tamponade in the emergency department presents special problems of diagnosis and management. Diagnosis is based on correlation of data from the history, physical examination, electrocardiogram, chest x-ray films, and a high index of suspicion. Echocardiography to confirm the diagnosis of tamponade and aid in correct placement of the needle in pericardiocentesis is especially helpful.

We studied the effect of a single oral dose of 40 mg of pentaerythritol tetranitrate (PETN) on the exercise capacity of ten patients with angina pectoris. The study design was a randomized double-blind crossover comparing the effects of 40 mg of oral PETN with placebo on exercise tolerance. Patients were exercised to moderate angina pectoris before and 2 1/2 and 4 1/2 hours after receiving the placebo or PETN at seven-day intervals during the double-blind crossover period. Exercise tolerance time was measured using a multistage, progressive treadmill test. Exercise times were greater 2 1/2 hours and 4 1/2 hours following PETN compared with placebo (P less than 0.05). Heart rate, systolic and diastolic blood pressure, and double product at rest (supine and standing) and at point of angina pectoris did not change significantly.

A group of 14 patients with mitral valve prolapse syndrome was referred for coronary angiographic study. The group was selected on the basis that all members had recurrent chest pain as their chief complaint and all had interpreted their chest pain as serious enough to warrant at lest two previous emergency visits to medical facilities in the six months preceding the study. All were found to have normal left ventricular function, and only one had a significant fixed obstructive coronary lesion. Seven of 14 patients (50 percent) showed evidence of coronary artery spasm during the catheterization study, five of whom had histories highly suggestive of coronary vasospasm. During the catheterization, spasm occurred spontaneously in three patients, ws ergonovine-induced in two, and was catheter-tip-induced in two. Ergonovine was administered to nine of the 14 patients. The drug induced vasospasm in two patients but failed in seven (two of whom had previously demonstrated catheter tip spasm). Of those seven patients who showed evidence of spasm, four had typical chest pain in association with reversible ST segment elevation and manifested a variant anginal syndrome.

A patient with traumatic hypoparathyroidism had cardiomyopathy and congestive heart failure. The patient had no history of preexisting cardiac disease, alcohol abuse, hyperthyroidism, or hypothyroidism and improved greatly with treatment of hypoparathyroidism. We suggest that the cardiomyopathy seen in hypoparathyroidism. We suggest that the cardiomyopathy seen in hypoparathyroidism is due to many factors, but that hypocalcemia and possibly hypomagnesemia are especially important, and that correction of calcium and magnesium deficiencies may result in near-normal cardiac function.

Platelet survival times were studied in 40 patients (21 white and 19 black) with coronary artery disease and stable effort induced angina pectoris. The platelet survival times of 19 white controls (9.27 +/- 0.49 days; mean +/- SD) were not significantly different from those of 12 black controls (8.88 +/- 0.81 days), and the platelet survival times for 21 white patients with coronary artery disease (8.46 +/- 0.65 days) were lower than the times for both the white controls (p less than 0.01) and the combined control group (p less than 0.01). However, the difference between the mean platelet survival times of 19 black patients (9.22 +/- 0.68) and the control groups was not significant, and the difference between the mean platelet survival times of the 21 white patients and the 19 black patients was significant (p less than 0.01). Stepwise multiple linear regression analysis indicated that race was the most significant factor in predicting shortened platelet survival (r = 0.4783; p less than 0.01). It is concluded that racial background should be considered in the interpretation of platelet studies and that reported racial differences in the rate and extent of atherosclerotic lesions may be related to racial differences in platelet consumption.

After intravenous bolus injections of clonidine HCl (150 micrograms) to 12 patients with congestive heart failure, peak effects appeared in 5 to 20 min. Clonidine reduced heart rate from 94 +/- 14 to 82 +/- 14 bpm (mean +/- SD, P less than 0.05), left ventricular filling pressure from 31 +/- 5 to 23 +/- 5 mm Hg (P less than 0.001), mean systemic arterial pressure from 98 +/- 13 to 82 +/- 13 mm Hg (P less than 0.001), mean pulmonary artery pressure from 46 +/- 6 to 38 +/- 6 mm Hg (P less than 0.001), and right atrial pressure from 14 +/- 5 to 11 +/- 5 mm Hg (P less than 0.05). Cardiac index increased from 1.6 +/- 0.4 to 1.8 +/- 0.6 l/min/m2 (P less than 0.05) and stroke volume from 32 +/- 10 to 43+/- 12 ml/beat (P less than 0.05). Systemic vascular resistance decreased from 2,342 +/- 800 to 1,795 +/- 345 dynes sec cm-5 (P less than 0.05) and pulmonary vascular resistance from 365 +/- 158 to 263 +/- 114 dynes sec cm-5 (P less than 0.05). We conclude that clonidine decreases heart rate and left ventricular preload and afterload in congestive heart failure.

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Hypocalcaemic cardiomyopathy is a rare form of dilated cardiomyopathy. The authors here present two cases in which symptomatic dilated cardiomyopathy was the result of severe hypocalcaemia. First, we report about a 26‐year‐old woman with primary hypoparathyroidism and then about a 74‐year‐old man with secondary hypoparathyroidism following a thyroidectomy. In both cases, the left ventricular systolic function improved after calcium supplementation. In the first case, a lack of compliance led to a repeated decrease of both serum calcium level and left ventricular systolic function. The authors also present a comprehensive summary of all cases of hypocalcaemic dilated cardiomyopathy that have been described in literature to date. The mean age of the affected patients was 48.3 years, of which 62% were female patients. The most common causes of hypocalcaemic cardiomyopathy are primary hypoparathyroidism (50%) and post‐thyroidectomy hypoparathyroidism (26%). In the post‐thyroidectomy subgroup, the median time for the development of hypocalcaemic cardiomyopathy is 10 years (range: 1.5 months to 36 years). Hypocalcaemic cardiomyopathy leads to heart failure with reduced ejection fraction in 87% of patients. Generally, the most common complications of hypoparathyroidism and/or hypocalcaemia are cerebral calcifications, cognitive deficit, and cataracts. Once calcium supplementation is administered, the disease has a good prognosis and, in most individuals, a significant improvement (21%) or even normalization (74%) of the left ventricular systolic function occurs. [ABSTRACT FROM AUTHOR]

During severe septic shock and/or severe acute respiratory distress syndrome (ARDS) patients present with a limited cardio-ventilatory reserve (low cardiac output and blood pressure, low mixed venous saturation, increased lactate, low PaO2/FiO2 ratio, etc.), especially when elderly patients or co-morbidities are considered. Rescue therapies (low dose steroids, adding vasopressin to noradrenaline, proning, almitrine, NO, extracorporeal membrane oxygenation, etc.) are complex. Fever, above 38.5-39.5°C, increases both the ventilatory (high respiratory drive: large tidal volume, high respiratory rate) and the metabolic (increased O2 consumption) demands, further limiting the cardio-ventilatory reserve. Some data (case reports, uncontrolled trial, small randomized prospective trials) suggest that control of elevated body temperature (“fever control”) leading to normothermia (35.5-37°C) will lower both the ventilatory and metabolic demands: fever control should simplify critical care management when limited cardio-ventilatory reserve is at stake. Usually fever control is generated by a combination of general anesthesia (“analgo-sedation”, light total intravenous anesthesia), antipyretics and cooling. However general anesthesia suppresses spontaneous ventilation, making the management more complex. At variance, alpha-2 agonists (clonidine, dexmedetomidine) administered immediately following tracheal intubation and controlled mandatory ventilation, with prior optimization of volemia and atrio-ventricular conduction, will reduce metabolic demand and facilitate normothermia. Furthermore, after a rigorous control of systemic acidosis, alpha-2 agonists will allow for accelerated emergence without delirium, early spontaneous ventilation, improved cardiac output and micro-circulation, lowered vasopressor requirements and inflammation. Rigorous prospective randomized trials are needed in subsets of patients with a high fever and spiraling toward refractory septic shock and/or presenting with severe ARDS. [ABSTRACT FROM AUTHOR]

Background The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study (‘CLEOPATRA’ study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. Methods and results A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. Conclusion Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity. [ABSTRACT FROM PUBLISHER]

Case reports have documented reversible cardiac dysfunction in the setting of severely depressed extracellular calcium concentrations. The present systematic review and meta-analyses of individual patient data were conducted to further characterize the cardiac dysfunction associated with low serum calcium levels in the clinical setting. We searched Ovid MEDLINE, Embase, PubMed databases and the Cochrane Library and the Registry of Clinical Trials from 1948 through August 2011. Studies that evaluated low serum calcium and cardiac dysfunction were identified and included for review. A total of 43 studies comprised of 47 individual cases met inclusion criteria. Univariate linear regression analysis showed a statistically significant correlation between corrected QT interval (QTc) length and corrected total serum calcium level ( B = −23.19, SE = 8.04, P = 0.01), left ventricular ejection fraction and corrected total serum calcium ( B = 5.16, SE = 1.29, P < 0.01) and ionized serum calcium ( B = 5.48, SE = 2.04, P = 0.03). Hypocalcemia may be associated with reversible cardiac dysfunction including QTc interval prolongation and depressed left ventricular systolic function. The available evidence is very limited and does not provide a rationale for a certain threshold or a recommendation for calcium replacement. Future research is needed in this important and common metabolic disorder. [ABSTRACT FROM AUTHOR]

Hypocalcemia secondary to hypoparathyroidism is a rare cause of congestive heart failure. However, its early recognition and treatment lead to significant improvement in cardiac function. We report a middle-aged woman presenting with symptoms of heart failure with a serum calcium level of 3.7 mg/dl and a serum inorganic phosphate level of 17.6 mg/dl 22 years after subtotal thyroidectomy. Besides calcium and calcitriol supplementation, she was the first patient with severe hypocalcemic cardiomyopathy to be given off-label recombinant human parathyroid hormone (PTH) because of an elevated serum calcium-phosphate product. We discuss the management and outcome of the patient and then present a brief review of similar previously reported cases. We also describe the pivotal role of calcium ion and the potential role of PTH in maintaining myocardial contractility, effective natriuresis, and possible pathogenic mechanisms contributing to heart failure secondary to hypocalcemia and hypoparathyroidism. [ABSTRACT FROM AUTHOR]

Laboratory efficiency is an important benchmark to achieve whether imaging is hospital-based or in the private practice setting. The stressor and imaging protocols used and the camera systems available for imaging all play a pivotal role toward this end. A same-day low-dose rest/high-dose stress imaging protocol has been widely adopted in nuclear cardiology laboratories. However, recent studies indicate that rest imaging may be unnecessary in patients with a normal initial stress single photon emission CT (SPECT) study. Appropriate elimination of rest imaging would decrease costs, streamline patient evaluations, and significantly reduce radiation exposure. Several recent studies have validated the safety of stress-only imaging in patients who have an initially normal perfusion study. Combined with new pharmacologic stressor agents and camera systems that can complete imaging within minutes, laboratory efficiency and patient satisfaction should improve considerably. The following article will review these currently available advances in SPECT imaging. [ABSTRACT FROM AUTHOR]

A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A database was assembled of fifty-six healthy subjects in whom total body noradrenaline spillover (indicative of whole body sympathetic nervous activity), brain noradrenaline spillover and brain lipophlic noradrenaline metabolite (3,4-dihydroxyphenolglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG)) overflow rates were measured. These measurements were also made following ganglion blockade (trimethaphan, n= 6), central sympathetic inhibition (clonidine, n= 4) and neuronal noradrenaline uptake blockade (desipramine, n= 13) and in a group of patients ( n= 9) with pure autonomic failure (PAF). The mean brain noradrenline spillover and brain noradrenaline metabolite overflow in healthy subjects were 12.5 ± 1.8, and 186.4 ± 25 ng min−1, respectively, with unilateral jugular venous sampling for both. Total body noradrenaline spillover was 605.8 ng min−1± 34.4 ng min−1. As expected, trimethaphan infusion lowered brain noradrenaline spillover ( P= 0.03), but perhaps surprisingly increased jugular overflow of brain metabolites ( P= 0.01). Suppression of sympathetic nervous outflow with clonidine lowered brain noradrenaline spillover ( P= 0.004), without changing brain metabolite overflow ( P= 0.3). Neuronal noradrenaline uptake block with desipramine lowered the transcranial plasma extraction of tritiated noradrenaline ( P= 0.001). The PAF patients had 77% lower brain noradrenaline spillover than healthy recruits ( P= 0.06), indicating that in them sympathetic nerve degeneration extended to the cerebral circulation, but metabolites overflow was similar to healthy subjects ( P= 0.3). The invariable discordance between noradrenline spillover and noradrenaline metabolite overflow from the brain under these different circumstances indicates that the two measures arise from different sources, i.e. noradrenaline spillover originates from the cerebral vasculature outside the blood–brain barrier, and the noradrenaline metabolites originate primarily from brain noradrenergic neurons. We suggest that measurements of transcranial plasma noradrenaline spillover have utility as a method for assessing the sympathetic nerve activity of the cerebral vasculature. [ABSTRACT FROM AUTHOR]

Despite the crucial role of calcium in myocardial contractility, hypocalcemia has very rarely been reported as a reversible cause of heart failure. In this article, we describe a case of a 51-year-old woman with advanced stages of chronic renal failure after parathyroidectomy who exhibited congestive heart failure, severe hypocalcemia, hypomagnesemia and hypokalemia. Severe hypocalcemia resulted from discontinuation of taking calcium supplements after parathyroidectomy and from reduced 1.25(OH)2D3 synthesis by damaged kidneys. The patient presented with reduced left ventricular ejection fraction (EF) and ECG abnormalities (T wave alternans and increased QTc dispersion), both of which improved after correction of serum calcium levels. Her serum levels of total calcium corrected for serum albumin, but not serum levels of magnesium or potassium, positively and negatively correlated with EF and QTc dispersion, respectively. In the present case, both heart failure and the ECG abnormalities are directly associated with hypocalcemia. [ABSTRACT FROM AUTHOR]

Omapatrilat (OMP) is a novel mixed inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP), the enzyme that metabolizes natriuretic peptides. Congestive heart failure (CHF) is characterized by excessive sodium retention, attributed to both an excessive effect of angiotensin II and diminished responsiveness to natriuretic peptides. In this study, we examined the acute and chronic renal and cardiac effects of OMP in rats with compensated [urinary sodium excretion (UNaV) > 1,200 µeq/day] and decompensated (UNaV < 100 µeq/day) CHF, induced by a surgical aortocaval fistula (ACF). Bolus injection of OMP (10 mg/kg) to sham controls produced significant diuretic and natriuretic responses [UNaV increased from 0.67 ± 0.19 to 3.27 ± 1.35 µeq/min, P < 0.05; fractional sodium excretion (FENa) increased from 0.23 ± 0.06 to 0.95 ± 0.34%, P < 0.01] despite a significant decline in blood pressure (BP). Rats with compensated CHF displayed blunted diuresis and natriuresis to this dose of OMP but a significant decrease in BP. However, in rats with decompensated CHF, OMP induced significant natriuresis (FENa increased from 0.18 ± 0.15 to 0.82 ± 0.26%, P < 0.05) despite a further decrease in BP (from 90 ± 9 to 71 ± 6 mmHg, P < 0.01). Two weeks after ACF, the heart/body weight ratio was significantly greater in rats with CHF than controls (0.51 ± 0.026 vs. 0.30 ± 0.004%, P < 0.0001), and UNaV was significantly lower. Immediate or late (1 or 6 days after ACF) OMP treatment in the drinking water (140 mg/l) reduced cardiac hypertrophy to 0.410.43% (P < 0.01) and induced natriuresis. These results suggest that OMP improves both sodium balance and cardiac remodeling and might be advantageous to ACE inhibitors for the treatment of decompensated CHF. [ABSTRACT FROM AUTHOR]

Activation of the sympathetic nervous system is well documented in heart failure. Our previous studies demonstrated an increase in evoked norepinephrine (NE) release from left ventricle (LV) slices at 10 days of pressure overload. The purpose of this study was to test the hypothesis that presynaptic modulation of NE release contributes to sympathetic activation after pressure overload. We examined the functional status of the presynaptic α2- and β2-receptors and ANG II subtype 1 (AT1) receptors in LV slices from 10-day aortic constricted (AC) and sham-operated (SO) rats. Evoked ³H overflow from LV slices preloaded with [3H]NE was increased in AC rats. The α2agonist UK-14,304 decreased evoked ³H overflow with no differences between groups. The β2-agonist salbutamol increased evoked ³H overflow with greater sensitivity in slices from AC rats. The β-antagonist propranolol decreased evoked ³H overflow from LV slices of AC rats but not controls. ANG II increased evoked ³H overflow with greater sensitivity in slices from AC rats. These data support the hypothesis that aberrant presynaptic modulation of catecholamine release contributes to sympathetic activation after pressure overload. [ABSTRACT FROM AUTHOR]

Hypocalcemic cardiomyopathy due to hypoparathyroidism is a very rare condition which is usually refractory to conventional treatment for cardiac failure but which responds favorably to restoration of normocalcemia. A 55-year-old man and a 46-year-old woman with a history of postoperative hypoparathyroidism presented with symptoms of cardiac failure and hypocalcemia. A presumptive diagnosis of dilated cardiomyopathy was considered by echocardiography and endomyocardial biopsies were consistent with cardiomyopathy. The coronary angiograms were normal and there was no apparent cause for dilated cardiomyopathy in these patients. The history of the patients and partial recovery of cardiac function after restoration of normocalcemia suggest that hypocalcemia was the cause of dilated cardiomyopathy.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the pharmacodynamics and pharmacokinetics of omapatrilat, administered orally (25 mg) or intravenously (10 mg) in 19 New York Heart Association class II and class III congestive heart failure (CHF) patients versus 17 healthy controls matched for age, race, gender, and weight. The plasma concentrations of atrial natriuretic peptide (ANP) increased by approximately 20% and 30% in CHF and control subjects, respectively, at 4 hours after intravenous or oral omapatrilat administration. Similar elevation in the cyclic guanosine monophosphate concentration (25% to 35%) and ANP urinary excretion (21 ng/24 h to 22 ng/24 h) was seen in all treatment groups after omapatrilat administration. Angiotensin-converting enzyme activity was > 90% inhibited at 4 hours after dosing and remained approximately 60% to 70% inhibited at 24 hours after dosing. The levels of endothelin-1 and endothelin-2 remained unchanged after oral or intravenous administration of omapatrilat. The maximal reduction in seated blood pressure compared with baseline was similar for CHF and control subjects. Clinical pharmacokinetic parameters were similar in both groups after intravenous dosing, but maximum concentration and area under the concentration-time curve were elevated in CHF patients compared with controls after oral dosing. Omapatrilat was well tolerated; differences in systemic exposure and metabolism between CHF patients and controls did not appear to be clinically significant. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 38-year-old man who had hyperparathyroidism secondary to end stage-renal-disease (ESRD). The patient underwent initial parathyroidectomy and was given doses of alfacalcidol prior to a second operation to prevent post-operative hypocalcaemia. Despite the doses administered, the patient continued to suffer atypical chest pains. It discusses the significance of intracellular calcium in myosin and actin filament activities.

Hypocalcemia is a rare, but reversible, cause of congestive heart failure. We report a 4-month-old boy diagnosed as dilated cardiomyopathy who had prolonged QoTc with low blood levels of calcium, normal phosphate, elevated alkaline phosphatase and findings suggestive of rickets. In view of non response to calcium and vitamin D3, a possible diagnosis of VDDR I (Vitamin D-dependent rickets) was made and he was treated with calcium and calcitriol. The serum calcium levels normalised within 10 days, along with resolution of the signs and symptoms of heart failure, near normal left ventricular function and normalisation of QoTc. Pediatricians should be aware of the association of hypocalcemia with cardiac dysfunction and should keep it as a possible reversible cause of heart failure in children. [ABSTRACT FROM AUTHOR]

The authors performed a randomized, double-blind, placebo-controlled trial to assess the tolerance and effects of chronic oral clonidine administration on the clinical status, exercise tolerance, and ventricular function of 10 male patients with chronic heart failure. Patients were given either oral clonidine (400 μg/day) or matching placebo for twelve weeks and then tapered off medication over a two-week period. Results are summarized as follows: Profiles over time between groups were significantly different for resting heart rate (p = 0.0005), were different for arterial pressure (p = 0.04), were different for left ventricular ejection fraction (p < 0.006), and were different for mean accumulated workload (p = 0.076). Exercise double product at 25 watts changed little in three patients and showed a decrease in 2 patients following six weeks of oral clonidine; after twelve weeks, it decreased in three patients, increased in 1, and changed little in another. After washout, double product returned toward baseline values. In the placebo groups, double product showed little change. Resting of the heart by decreasing heart rate, systemic arterial blood pressure, and venous tone are thought by the authors to be major contributing factors to the observed beneficial effect of chronic oral clonidine in chronic heart failure. [ABSTRACT FROM AUTHOR]

The association between mitral valve prolapse (MVP) and atypical chest pain has been well-described. Numerous theories have been proposed to explain this association. A number of lines of evidence suggest that underlying ischemia may cause chest pain in some patients with MVP. We have recently evaluated 4 patients with chest pain syndromes who had angiographic evidence of MVP and spasm of angiographically normal coronary arteries. The possibility that coronary spasm is the underlying, etiology of chest pain in some patients with mitral valve prolapse raises a theoretical argument against β-blockade in these patients. Three of our patients were successfully treated with calcium channel blockers. [ABSTRACT FROM AUTHOR]

Hypocalcemia is a curable cause of myocardial dysfunction and clinical congestive cardiac failure, with only stray reports available in literature. We describe 15 infants presenting with severe left ventricular dysfunction, who were found to have hypocalcemia with or without hypomagnesemia. Vitamin D deficiency was identified as the main cause of hypocalcemia. These children improved on supplementation of vitamin D and calcium. [ABSTRACT FROM AUTHOR]

SUMMARY 1. The autonomic nervous system plays a pivotal role in modulating all the components of the cardiovascular regulation. Therefore, one can assume that drugs targeting this system may be useful in the management of several cardiovascular diseases. 2. Drugs acting on central nervous system centres seem to be modulators rather than blockers; as such, they are expected to preserve the contraregulatory processes and to generate only a few side effects. 3. Because the sympathetic nervous system is largely involved in the regulation of vasomotor tone, centrally acting antihypertensive drugs were developed first. 4. Recently, new leader compounds selective for non- adrenergic imidazoline recepetors have been synthetized. Although such drugs have no capacity to activate α2-adrenoceptors, they have been proven to be hypotensive. These drugs are expected to be even better tolerated than the currently available centrally active drugs. They may also have additional beneficial effects. 5. Here, the experimental evidence suggesting that such drugs may be useful in the management of some cardiac arrhythmias and/or left ventricular dysfunction will be reviewed. [ABSTRACT FROM AUTHOR]

Assesses the use of sympathetic suppression in chronic heart failure. Factors in determining the impact of a therapeutic approach; Discussion on the pathogenic mechanism of heart failure; Treatment for heart failure.

A letter to the editor is presented which reports a case of hypoparathyroidism with severe hypocalcemia, intracranial calcification, psychosis, and reverse dilated cardiomyopathy.