Metabolic abnormalities following heart transplantation in patients with idiopathic cardiomyopathy

The purpose of this study was to evaluate the risk factors for coronary artery disease associated with initiation of immunosuppressive therapy in patients with a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July 1992 to June 1993. All patients were treated with cyclosporine, azathioprine and prednisolone, and the following measurements were performed prior to hospital discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1) fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and insulin concentrations in response to a 75 g oral glucose challenge; and 3) steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI concentrations are similar in all individuals, the SSPG concentrations provide an estimate of the ability of insulin to stimulate glucose disposal. Only six of the patients had a normal oral glucose tolerance test and the following diagnoses were found in the remaining nine patients: not diagnised (n = 3), impaired glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma lipid and lipoprotein concentrations were also frequently abnormal in the heart transplant patients; eight of the 15 patients had a plasma cholesterol > 5 mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1 mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value rarely exceeded in healthy volunteers. In conclusion, significant metabolic abnormalities were present at discharge in patients who had undergone successful cardiac transplantation for idiopathic cardiomyopathy. These metabolic abnormalities were probably caused by the use of immunosuppressive drugs. Given the magnitude of these changes, it would seem prudent to initiate therapeutic programs in patients with cardiac transplants that are not simply aimed at preventing rejection, but also address the metabolic abnormalities associated with the immunosuppressive agents used to prolong allograft survival.     

Muscle abnormalities in idiopathic toe-walkers

The authors report 12 cases of bilateral cupulolithiasis found in 142 subjects diagnosed as having benign paroxysmal positional vertigo. A case history was taken for these patients (4 males, 8 females; average age 28 years) and 10 reported a previous cranial trauma while the remainder did not refer any previous condition of note. All patients had normal cochleovestibular test results and showed no signs of concomitant internal and/or central pathologies. The Hallpike maneuver was able to evoke an intense symmetrical paroxysmal vertigo and this was often accompanied by neurovegetative phenomena while paroxysmal nystagmus always appeared. The patients were treated with a rehabilitative technique: the Brandt-Daroff was preferred as it is better tolerated. Within 15 days all patients had full remission of symptoms and at 6 months after treatment there have been no signs of recurrence. The conclusion is, thus, drawn that while the technical characteristics of the Sémont maneuver make it suitable only for use as rehabilitation in unilateral benign paroxysmal positional vertigo, this experience indicates that the Brandt-Daroff technique is better suited for the bilateral forms of this disorder.     

Significance of mental factors in paroxysmal ventricular tachycardias]

In this paper is reported on two cases of paroxysmal ventricular tachycardia. The clinical and paraclinical examinations did not reveal any organic heart disease, the psychological one, however, found a very severe neurotic personality disorder. Antiarrhythmic drugs were ineffective in both cases. Meanwhile one female patient went through a brief psychotherapy which dismissed the arrhythmia.     

Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy

BACKGROUND: To define the electrophysiological mechanism(s) of inducible and spontaneously occurring ventricular arrhythmias associated with nonischemic cardiomyopathy, 3-dimensional intraoperative mapping from 156 intramural sites was performed in 6 patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation. METHODS AND RESULTS: Electrode density was sufficient to determine the mechanism for 52 of 74 beats of nonsustained ventricular tachycardia (VT) induced by programmed stimulation and 9 of 11 beats of spontaneous ventricular arrhythmias. The first, second, and third extrastimuli (S2 through S4) conducted with progressively greater degrees of conduction delay (total activation times [TAs] of 144+/-5, 166+/-5, and 194+/-5 ms, respectively) owing to slow conduction and on occasion intramural block. The first beats of induced VT arose from subendocardial or subepicardial sites distant from areas of marked conduction delay by a focal mechanism on the basis of the absence of intervening electrical activity between the termination of the last extrastimulus and the initiation of VT (123+/-31 ms). Subsequent beats arose by a focal mechanism and conducted with a TA of 127+/-6 ms (P=NS versus initiating beats of VT [118+/-9 ms]). Spontaneous ventricular arrhythmias initiated in the subendocardium by a focal mechanism and conducted with a TA of 138+/-5 ms. Tissue analysis demonstrated a variable degree of interstitial fibrosis at sites of focal activation. Sites of conduction delay or block typically exhibited marked interstitial and/or replacement fibrosis but were spatially distant from sites initiating VT. CONCLUSIONS: Spontaneous and induced ventricular arrhythmias in patients with end-stage idiopathic cardiomyopathy can arise in the subendocardium or subepicardium by a focal mechanism.     

Association between hemodynamic parameters and the degeneration of sustained ventricular tachycardias into ventricular fibrillation in rats

Sustained ventricular tachycardias (VT) often degenerate into ventricular fibrillation (VF). In the present study, the impact of VT on mean arterial blood pressure (MAP), myocardial blood flow (MBF), and myocardial oxygen consumption (MVCO2) was assessed. In addition, the degeneration of sustained VT into VF was analysed with respect to MAP. MBF was measured in 48 anesthetized rats with colored microspheres; arterial catecholamine levels were measured by HPLC in 16 additional rats during control conditions and VT. MBF (4. 66+/-1.29 ml/g/min; mean+/-s.d.) did not change with the onset of VT (5.37+/-1.92 ml/g/min, n.s.). Epinephrine (0.22+/-0.13 ng/ml) and norepinephrine (0.37+/-0.12 ng/ml) increased during VT (3.55+/-2.68 ng/ml, P<0.01; 0.88+/-0.44 ng/ml, P<0.05), respectively. VF was more frequent when MAP remained normal (MAP>80 mmHg: 26%) than with hypotension (MAP<80 mmHg: 2%, P<0.05). Mechanical failure was observed in 10% of rats with severe hypotension (MAP<60 mmHg), and 2% with moderate hypotension (MAP 60-80 mmHg). The endo-epicardial MBF ratio in the VF group was significantly lower than that in the non-VF group (0.94+/-0.17 v 1.11+/-0.24, P<0.05). Conclusions: severe hypotension predisposes to the occurrence of acute mechanical failure during VT; moderate hypotension during VT, however, serves as a protective mechanism against VF in structurally normal hearts. Subendocardial hypoperfusion in the presence of an increased energy demand during VT is suggested to be responsible for the initiation of VF.     

CSF abnormalities in patients with aceruloplasminemia

Aceruloplasminemia is a disorder of iron metabolism characterized by degeneration of the retina and basal ganglia. CSF from affected patients showed a threefold increased iron concentration that was associated with increased superoxide dismutase activity and lipid peroxidation products. These findings support the hypothesis that iron-mediated lipid peroxidation contributes to neurodegeneration in patients with aceruloplasminemia. Such measurements may have value in assessing disease progression as well as the results of iron chelation and other therapeutic interventions.     

Radionuclide (MUGA) studies of left ventricular functional abnormalities in asymptomatic patients with sickle cell anemia

Radionuclide ventriculography was performed on 10 normal subjects and 39 patients with sickle cell anemia (10 homozygous and 29 heterozygous sicklers) at rest and after exercise. Their left ventricular (LV) function was assessed in both these situations. The results were then compared within the subgroups. The reduction in ejection fraction (EF) response (47.5 +/- 7 at rest and 46.4 +/- 8 at exercise in homozygous patients, and 52.4 +/- 8 at rest and 54.3 +/- 8 at exercise in heterozygous patients) was significant in both the homozygous and the heterozygous groups but more so in the former group. The diastolic filling was also significantly impaired in the homozygous group (PER 2.64 +/- 0.74, PFR 2.13 +/- 0.42 and PFR/HR 0.014 +/- 0.001). The study statistically demonstrates, that LV filling patterns are altered in the sickle cell patients, even in the absence of clinical symptoms relating to LV dysfunction. This fact may prove to be a marker of sickle cell heart disease. Frequent and significant sickling is probably the cause of more pronounced LV functional abnormalities in homozygous sicklers.     

Gastrointestinal transit in patients with idiopathic megarectum

PURPOSE: In patients with idiopathic megarectum, it is unknown whether abnormality is limited to the dilated large bowel or whether the upper gut is abnormal, as in the various forms of chronic intestinal pseudo-obstruction. This has important implications for treatment, especially surgery. METHODS: Ten patients (4 females; median age, 18 (range, 17-26) years) with idiopathic megarectum had contrast studies of the upper and lower gut, radioisotope (technetium-99m liquid and indium-111 solid phase) measurement of gastric, small-bowel, and colonic regional transit, and radiopaque marker colonic studies. RESULTS: All patients had a dilated large bowel. No patient had radiographic evidence of upper gut dilation. Four patients had normal and six patients had abnormally slow gastric emptying. Both the radioisotope scans and radiopaque marker studies showed abnormal colonic transit. Regions of delay corresponded with the region of dilated bowel. Symptoms of abdominal distention and bloating did not correspond to abnormalities of gastric emptying but rather with effectiveness of rectal evacuation. CONCLUSION: Patients with idiopathic megarectum have abnormal colonic transit, delay occurring predominantly in the dilated gut. Marker studies are less sensitive than isotope studies but provide adequate information for clinical purposes. Although motility abnormalities of the upper gut are common, symptoms correlate with large-bowel abnormalities.     

Termination of ventricular tachycardia in the human heart. Insights from three-dimensional mapping of nonsustained and sustained ventricular tachycardias

BACKGROUND: To define the electrophysiological basis for the termination of ventricular tachycardia (VT), three-dimensional cardiac mapping and analysis of the terminal beats of nonsustained VT and beats of sustained VT were performed in six patients with healed myocardial infarcts. METHODS AND RESULTS: Termination of VT was due to activation from multiple initiation sites that were discordant from those responsible for the maintenance of sustained VT in 45% of cases, to repetitive activation from single sites that were discordant from those responsible for the maintenance of sustained VT in 24% of cases, or to activation from sites concordant with the sites of repetitive activation during sustained VT in 31% of cases. Sustained VT was characterized by occasional shifting of initiation sites, even after the tachycardia entered the stable monomorphic phase. Mapping was of sufficient density to define the mechanisms for 21 terminating beats of VT. In 5 cases, termination was due to intramural reentry, which initiated with the total activation time of the preceding beat of 204 +/- 11 milliseconds (ms) but terminated primarily because of a decrease in total activation time (144 +/- 23 ms, P = .03) that was associated with the development of intramural conduction block or with significant changes in the activation sequence along the reentrant circuit. In 16 cases, terminal beats were initiated by a focal mechanism on the basis of the absence of intervening electrical activity from the termination of the preceding beat to the initiation of the terminating beat (172 +/- 9 ms). Focal activation was associated with less conduction delay of the preceding beat (115 +/- 6 ms) than terminating reentrant beats (P < .001) and usually terminated suddenly without oscillations in cycle length or total activation time. CONCLUSIONS: Termination of VT is associated with alterations in initiation sites that are most often discordant from those maintaining sustained VT and is due to either reentrant or focal mechanisms.     

Radiofrequency catheter ablation of multiple haemodynamically unstable ventricular tachycardias in a patient with surgically repaired tetralogy of Fallot

A 55-year-old man was admitted following an overdose of sustained-release verapamil (calcium channel blocker) and ordinary-release atenolol (beta-1 blocker). At admission, there was extreme bradycardia (20-25 beats min-1) and hypotension (systolic arterial pressure 40-50 mm Hg). To counteract the cardiovascular depression, prenalterol, dopamine, dobutamine, isoprenaline, adrenaline and noradrenaline were used. A satisfactory state was obtained with adrenaline, noradrenaline and dopamine infused at high rates. Cardiac output was then more than 101 min-1, with a very low total peripheral resistance. The infusion of the adrenergic agonists could be interrupted on day 3. Prolonged ventilator treatment was necessary but the patient recovered without sequelae. Treatment options for similar cases are outlined.     

Immunoglobulin abnormalities in epileptic patients treated with diphenylhydantoin

An immunologic study was made on 170 epileptic patients treated with antiepileptic drugs. The most noteworthy finding was that the serum IgA was decreased in 22 patients, and an IgA deficiency noticed in 12 of them. The blastic transformation rate of lymphocytes in PHA-containing cultures appeared low in seven out of 12 patients. Other findings included decreased serum IgM and IgG in some patients. These abnormalities were not encountered in epileptic patients taking no anti-epileptic drugs. Therefore, they could be considered as the side effects of antiepileptic drugs. In all patients manifesting these abnormalities, diphenylhydantoin was used in common. It was surmised that the above-mentioned immunologic abnormalities caused by anti-epileptic drugs, especially diphenylhydantoin, had resulted from disorders of the antibody producing organs in the bone marrow-thymus-lymphatic system.     

Biliary tract abnormalities in patients with arteriohepatic dysplasia

Arteriohepatic dysplasia is a congenital syndrome associated with life-long cholestasis. Because of symptoms suggesting extrahepatic biliary tract obstruction, we studied three patients with this syndrome by endoscopic retrograde cholangiopancreatogram (ERCP). All patients showed a decrease in the number of intrahepatic ducts. In addition, the intrahepatic ducts show attenuation with focal areas of dilatation. In one subject, this latter finding appeared to be a localized process. The extrahepatic ducts were also narrowed. One patient in this series was found to have gallstones and another cirrhosis. Although the relationship of these anomalies to the cholestasis seen in these patients is unclear, arteriohepatic dysplasis can be added to the list of processes associated with biliary tract abnormalities.     

Cytogenetic abnormalities in patients with severe aplastic anemia

BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.     

Metabolic abnormalities in patients with caliceal diverticular calculi

PURPOSE: We determined the incidence and spectrum of metabolic abnormalities in patients with caliceal diverticular calculi. MATERIALS AND METHODS: Five men and 9 women with caliceal diverticular calculi underwent metabolic evaluation, including determination of serum electrolytes, calcium, phosphate and uric acid, and 24-hour urinary volume, creatinine, calcium, oxalate, uric acid and citrate. RESULTS: Of the 14 patients 7 (50%) had urinary excretion abnormalities promoting stone formation, including hypercalciuria in 3, hyperoxaluria in 1, hypercalciuria combined with hyperuricosuria in 1 and hyperoxaluria combined with hyperuricosuria in 2. Two patients had a history of gout while another had radiographic evidence of medullary sponge kidney. Of the patients 9 (64.3%) had a history of synchronous or metachronous calculi distant from the involved caliceal diverticular stone and 5 (55.6%) of these 9 had definable metabolic disorders. However, there was no statistically significant difference in urinary excretion values between patients with or without a history of additional extra diverticular stones. CONCLUSIONS: Urinary stasis alone does not explain stone formation in a significant number of patients with caliceal diverticular calculi. Rather, the local physiological environment of the urine likely has a predisposing role and evaluation for metabolic abnormalities should be considered. In some patients cure may be effected by treating the stone and any associated metabolic disorders rather than the diverticulum.     

Improved metabolic control does not reverse left ventricular filling abnormalities in newly diagnosed non-insulin-dependent diabetes patients

In this study left ventricular diastolic function at rest was evaluated in ten newly diagnosed, non-insulin-dependent diabetic patients by Doppler echocardiography, performed at the onset of disease and after 6 and 12 months of adequate glycaemic control. Glycosylated haemoglobin A1C, total cholesterol and triglyceride levels were assessed at the same time. The control group consisted of ten healthy subjects of matching age and body mass index. The following parameters of left ventricular function were evaluated: ejection fraction (EF), peak velocity of the early (E) and late atrial (A) mitral flow, A/E ratio, duration of the early (Ei) and of the atrial (Ai) filling phase, and heart rate. The diabetic patients had significantly higher total cholesterol and triglyceride levels compared with healthy subjects. These remained elevated throughout the follow-up period, in spite of improved glycaemic control. A significantly shorter duration of Ei (0.15 +/- 0.008 vs 0.18 +/- 0.004, P < 0.01) and a higher value of A (0.51 +/- 0.02 vs 0.39 +/- 0.01, P < 0.001) and A/E (1.06 +/- 0.05 vs 0.73 +/- 0.02, P < 0.001) were found in the diabetic patients before treatment. The parameters did not significantly change after 1 year of adequate glycaemic control. These results indicate a left ventricular filling abnormality which is present in newly diagnosed non-insulin-dependent diabetic patients and does not reverse with improved glycaemic control.     

Circannual variation of malignant ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators and either coronary artery disease or idiopathic dilated cardiomyopathy

We studied the possible relation between the frequency of ventricular tachyarrhythmic events and thermal stress in patients with an implantable cardioverter-defibrillator (ICD) living in a locally limited area under homogeneous climatic conditions. The frequency of tachyarrhythmic events was correlated with the thermal stress level according to the "Klima Michel Model," a complete thermophysiologic model that calculates "felt-temperature" values on the basis of the outdoor temperature and further meteorologic data. During a mean follow-up time of 40 +/- 17 months (range 4 to 72), 761 ventricular tachyarrhythmic events occurred in 50 of 138 consecutive ICD recipients. Analysis of the monthly felt-temperature levels and the mean circannual variation of the registered ventricular arrhythmias suggested that very cold and very hot conditions may be associated with an increased frequency of ventricular tachyarrhythmias. This finding was confirmed by calculation of the sum of tachyarrhythmias on all 2,039 days of the follow-up period divided into 5-degree-step felt-temperature classes. Thus, thermal stress may be 1 factor triggering the occurrence of ventricular tachyarrhythmias in patients with cardiac disease and suppressed cardiac function. Part of the increase in cardiac mortality under above-average hot and cold atmospheric conditions may be attributed to ventricular arrhythmic events.     

Atrial conduction abnormalities in patients with systemic progressive sclerosis

BACKGROUND: Atrial abnormalities in patients with progressive systemic sclerosis have not been evaluated in terms of intra-atrial conduction. We hypothesized that a delay in atrial conduction in these patients might produce diastolic abnormalities as well as atrial arrhythmias. OBJECTIVE: To evaluate the atrial function of patients with progressive systemic sclerosis by using echocardiography to measure the intra-atrial electromechanical activation coupling interval. METHODS: Twenty patients with progressive systemic sclerosis were assessed by Doppler echocardiography. Twenty age-matched healthy controls were also evaluated. Two-dimensional guided M-modes of ventricular long axes were recorded using simultaneous phono- and electrocardiograms of the apical four chamber view at the right lateral, septal and left lateral sites of the atrioventricular rings. Transmitral and tricuspid pulsed Doppler flow velocities were also recorded. Filtered P wave duration was measured on the signal averaged ECG to determine the duration of atrial electrical activation. RESULTS: There was a delay in P on the electrocardiogram (P) at the onset of atrial contraction on long axis M-modes at all three atrioventricular ring sites in patients with progressive systemic sclerosis as compared with controls (P-right; 56 +/- 13 vs 47 +/- 10 ms, P-septal; 74 +/- 14 vs 55 +/- 10 ms, and P-lateral; 93 +/- 16 vs 72 +/- 11 ms, P < 0.01). Inter-atrial conduction time [(P-lateral)-(P-right)] was delayed in patients with progressive systemic sclerosis, compared with healthy controls (37 +/- 15 vs 25 +/- 6 ms, P < 0.01). Mitral A waves acceleration and deceleration times were also decreased in the patients. The interval was prolonged between P to the onset and the peak of the A wave in transmitral flow. Duration of the filtered P wave was significantly prolonged in progressive systemic sclerosis as compared with controls (124 +/- 12 ms vs 106 +/- 8 ms, P < 0.01). PQ intervals, E waves and acceleration and deceleration times did not differ significantly in progressive systemic sclerosis vs, controls. The A wave acceleration rate on transmitral flow (peak A wave velocity/acceleration time) showed a significant correlation with inter-atrial conduction delay (r = 0.55, P < 0.01). CONCLUSIONS: Intra-atrial electromechanical coupling intervals were delayed in patients with progressive systemic sclerosis. Thus, the mechanical late diastolic filling time due to atrial contraction in the total diastolic phase was severely limited, and this resulted in a restricted mitral A wave. We should therefore evaluate patients with progressive systemic sclerosis for significant atrial abnormalities.     

Nursing care of patients with idiopathic parkinsonism

Through the discussion of the work of a movement disorder clinic in British Columbia, this paper focuses on the unique contribution of nursing care in the effective management of idiopathic parkinsonism. It follows on from a paper discussing the aetiology and treatment of the disease published on April 20 in Nursing Times.