Absence Of Cardiac Dysfunction Research Articles

Spontaneous closure of perimembranous ventricular septal defect in a cat

We discuss the case of a 5-month-old male British Shorthair referred to our hospital following the detection of a heart murmur during a routine vaccination appointment. Two-dimensional echocardiography revealed a 1.18 mm ventricular septal defect (VSD) located immediately below the aortic valve, without signs of secondary cardiac remodeling. Given the absence of cardiac dysfunction, no treatment was administered, and the cat was periodically monitored over the next 2 years. Echocardiography at 29 months of age revealed no signs of the VSD. Future studies are needed to increase the evidence base for spontaneous VSD closure in small animals.

Systemic under treatment of heart disease in patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy is a devastating muscle disease characterized by muscle deterioration and cardiomyopathy. The cardiomyopathy is progressive in nature, marked by the accumulation of myocardial scarring and the loss of contractile function. The presence of cardiac disfunction is nearly universal in individuals with Duchenne muscular dystrophy with dysfunction being evident in patients < 10 years of age. In recognition of importance of prophylactic treatment, clinical guidelines recommend beginning treatment of the heart disease in Duchenne muscular dystrophy patients at 10 years of age, even in the absence of cardiac dysfunction. This manuscript evaluates the current practices of treatment of dystrophic cardiomyopathy. We make use of clinical data compiled by the Muscular Dystrophy Association to assess changes in medical management of cardiac disease in Duchenne muscular dystrophy patients in response to changes in guidelines. We find since the issuance of new guidelines Duchenne muscular dystrophy patients receiving cardiac-directed therapy are beginning it at significantly younger ages. However, we show that 64 % of individuals with Duchenne muscular dystrophy are not receiving the recommended cardiac therapies. The underlying causes of this gap in guideline adherence are complex but correcting this deficiency represent a significant opportunity to improve the clinical management of dystrophic cardiomyopathy.

Cardiac dysfunction in patients affected by subarachnoid haemorrhage affects in-hospital mortality: A systematic review and metanalysis.

Subarachnoid haemorrhage (SAH) is a life-threatening condition with associated brain damage. Moreover, SAH is associated with a massive release of catecholamines, which may promote cardiac injury and dysfunction, possibly leading to haemodynamic instability, which in turn may influence a patient's outcome. To study the prevalence of cardiac dysfunction (as assessed by echocardiography) in patients with SAH and its effect on clinical outcomes. Systematic review of observational studies. We performed a systematic search over the last 20 years on MEDLINE and EMBASE databases. Studies reporting echocardiography findings in adult patients with SAH admitted to intensive care. Primary outcomes were in-hospital mortality and poor neurological outcome according to the presence or absence of cardiac dysfunction. We included a total of 23 studies (4 retrospective) enrolling 3511 patients. The cumulative frequency of cardiac dysfunction was 21% (725 patients), reported as regional wall motion abnormality in the vast majority of studies (63%). Due to the heterogeneity of clinical outcome data reporting, a quantitative analysis was carried out only for in-hospital mortality. Cardiac dysfunction was associated with a higher in-hospital mortality [odds ratio 2.69 (1.64 to 4.41); P < 0.001; I2 = 63%]. The GRADE of evidence assessment resulted in very low certainty of evidence. About one in five patients with SAH develops cardiac dysfunction, which seems to be associated with higher in-hospital mortality. The consistency of cardiac and neurological data reporting is lacking, reducing the comparability of the studies in this field.

Genetic architecture of left ventricular noncompaction in adults

The genetic etiology and heritability of left ventricular noncompaction (LVNC) in adults is unclear. This study sought to assess the value of genetic testing in adults with LVNC. Adults diagnosed with LVNC while undergoing screening in the context of a family history of cardiomyopathy were excluded. Clinical data for 35 unrelated patients diagnosed with LVNC at ≥18 years of age were retrospectively analyzed. Left ventricular (LV) dysfunction, electrocardiogram (ECG) abnormalities, cardiac malformations or syndromic features were identified in 25 patients; 10 patients had isolated LVNC in the absence of cardiac dysfunction or syndromic features. Exome sequencing was performed, and analysis using commercial panels targeted 193 nuclear and mitochondrial genes. Nucleotide variants in coding regions or in intron-exon boundaries with predicted impacts on splicing were assessed. Fifty-four rare variants were identified in 35 nuclear genes. Across all 35 LVNC patients, the clinically meaningful genetic diagnostic yield was 9% (3/35), with heterozygous likely pathogenic or pathogenic variants identified in the NKX2-5 and TBX5 genes encoding cardiac transcription factors. No pathogenic variants were identified in patients with isolated LVNC in the absence of cardiac dysfunction or syndromic features. In conclusion, the diagnostic yield of genetic testing in adult index patients with LVNC is low. Genetic testing is most beneficial in LVNC associated with other cardiac and syndromic features, in which it can facilitate correct diagnoses, and least useful in adults with only isolated LVNC without a family history. Cardiac transcription factors are important in the development of LVNC and should be included in genetic testing panels.

Utilization of deceased donors during a pandemic: argument against using SARS-CoV-2-positive donors.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID‐19)–positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19–positive donors. The factors we consider include (1) the risk of blood transmission of SARS‐CoV‐2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.

Distinct Cellular Basis for Early Cardiac Arrhythmias, the Cardinal Manifestation of Arrhythmogenic Cardiomyopathy, and the Skin Phenotype of Cardiocutaneous Syndromes.

Arrhythmogenic cardiomyopathy is caused primarily by mutations in genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and typically early manifestations, whereas myocardial fibroadiposis is the pathological hallmark. Homozygous DSP (desmoplakin) and JUP (junction protein plakoglobin) mutations are responsible for a subset of patients with arrhythmogenic cardiomyopathy who exhibit cardiac arrhythmias and dysfunction, palmoplanter keratosis, and hair abnormalities (cardiocutaneous syndromes). To determine phenotypic consequences of deletion of Dsp in a subset of cells common to the heart and skin. Expression of CSPG4 (chondroitin sulfate proteoglycan 4) was detected in epidermal keratinocytes and the cardiac conduction system. CSPG4pos cells constituted ≈5.6±3.3% of the nonmyocyte cells in the mouse heart. Inducible postnatal deletion of Dsp under the transcriptional control of the Cspg4 locus led to ventricular arrhythmias, atrial fibrillation, atrioventricular conduction defects, and death by 4 months of age. Cardiac arrhythmias occurred early and in the absence of cardiac dysfunction and excess cardiac fibroadipocytes, as in human arrhythmogenic cardiomyopathy. The mice exhibited palmoplantar keratosis and progressive alopecia, leading to alopecia totalis, associated with accelerated proliferation and impaired terminal differentiation of keratinocytes. The phenotype is similar to human cardiocutaneous syndromes caused by homozygous mutations in DSP. Deletion of Dsp under the transcriptional regulation of the CSPG4 locus led to lethal cardiac arrhythmias in the absence of cardiac dysfunction or fibroadiposis, palmoplantar keratosis, and alopecia, resembling the human cardiocutaneous syndromes. The findings offer a cellular basis for early cardiac arrhythmias in patients with arrhythmogenic cardiomyopathy and cardiocutaneous syndromes.

Beyond Mitophagy: The Diversity and Complexity of Parkin Function.

Parkin is an E3 ubiquitin ligase that mediates mitochondrial autophagy, or mitophagy, in multiple cell types. Although discovered in the context of Parkinson disease, Parkin is also an important regulator of mitophagy in the heart. In addition, while most current work is focused on the role of Parkin in mitophagy, accumulating evidence suggests that Parkin also impacts cellular physiology and function through additional processes. This Viewpoint discusses current controversies on the functional role of Parkin-mediated mitophagy and emerging evidence that Parkin regulates several additional pathways. Ubiquitylation is a post-translational modification that involves covalently attaching ubiquitin to target proteins.1 The process of ubquitylation requires a series of events including ubiquitin activation, conjugation, and ligation, catalyzed by E1, E2, and E3 enzymes, respectively. Parkin is one of >500 E3 ubiquitin ligases encoded by the human genome that selectively bestows ubiquitin molecules onto particular proteins. One of Parkin’s most widely appreciated roles is the ubiquitylation of proteins on the membrane of damaged mitochondria to designate them for clearance via mitophagy. Mitophagy is a selective form of macroautophagy that traffics damaged mitochondria to lysosomes for degradation and serves as a critical mechanism in maintaining the health of the mitochondrial collective in a cell. Although it is clear that mutations that impair Parkin’s E3 ligase function contribute to the attrition of dopaminergic neurons through cell death in Parkinson disease,2 the underlying mechanisms are still not fully understood and there is no direct evidence that a defect in mitophagy is the underlying cause of Parkinson disease. The assumption that faulty mitophagy is responsible for Parkinson disease stems from observations that defects in mitochondrial morphology and function are key features of Parkinson disease2 and that loss of Parkin in Drosophila leads to mitochondrial dysfunction and muscle degeneration.3 When combined with the seminal work …

Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction

As aging is a significant risk factor for the development of left ventricular hypertrophy and cardiovascular disease, we hypothesized that hearts from middle-aged mice may be more sensitive to the effects of a high fat (HF) diet than hearts from young mice. To investigate this, young (10-12week old) and middle-aged (40-44week old) male mice were fed a low fat (LF) or HF diet (10 or 60kcal% fat, respectively) for 12weeks. Following this 12-week period, we show that CD36 protein expression was not changed in hearts from young mice yet was increased 1.5-fold in the middle-aged HF group compared with LF-fed age-matched counterparts. Correlated with increased CD36 expression, middle-aged mice displayed a greater degree of cardiac hypertrophy compared with young mice when fed a HF diet, and this was observed in the absence of cardiac dysfunction. Furthermore, middle-aged CD36 knockout mice were protected against HF diet-induced cardiac hypertrophy, supporting a link between CD36 and cardiac hypertrophy. To further explore potential mechanisms that may explain why middle-aged mice are more susceptible to HF diet-induced cardiac hypertrophy, we investigated mediators of cardiac growth. We show that myocardial ceramide levels were significantly increased in middle-aged mice fed a HF diet compared with LF-fed controls, which was also correlated with inhibition of AMP-activated protein kinase (AMPK). Consistent with AMPK being a negative regulator of cardiac hypertrophy, decreased AMPK activity also resulted in the activation of the mTOR/p70S6K pathway, which is known to enhance protein synthesis associated with cardiac hypertrophy. Together, these data suggest that increased myocardial CD36 expression in hearts from middle-aged mice may contribute to HF diet-induced cardiac hypertrophy and that this may be mediated by elevated ceramide levels signaling through AMPK. Overall, we suggest that inhibition of CD36-mediated fatty acid uptake may prevent obesity-related cardiomyopathies in the middle-aged population.

Dynamics of Extravascular Pulmonary Water and Intracranial Pressure in Patients With Ischemic Stroke

The objective of the present study was to examine the relationship among extravascular pulmonary water, intracranial and cerebral perfusion pressure, hemodynamic parameters (eg, cardiac index, system vascular resistance index), and brain stem function during acute ischemic stroke. The subjects were 17 comatose patients with ischemic stroke who were admitted to an intensive care unit. The results revealed an elevation in extravascular lung water in the absence of cardiac dysfunction. The absence of correlation between indices of brain vascular resistance and mean arterial pressure confirmed that a disturbance of cerebral blood flow was present. There was a correlation between auditory-evoked potential parameters and extravascular lung water during the study period. The correlation between auditory-evoked potentials and extravascular lung water may imply that ischemic brainstem injury plays a significant role in the development of increased pulmonary capillary permeability and the elevation of extravascular lung water. Brain stem injury is a cause of noncardiogenic lung edema in comatose patients following acute ischemic stroke.

Local modulation of the natriuretic peptide system in the rat remnant kidney

The natriuretic peptide (NP) system plays a central role in the renal adaptations to acute volume expansion. However, the modulation of the NP system in chronic renal insufficiency (CRI) remains to be elucidated. In the present study, we evaluated cardiac haemodynamics, plasma type-B natriuretic peptide (BNP) levels and the expression of natriuretic peptide receptor A (NPR-A) and NPR-C in the renal cortex (RC) and medulla (RM) of Sham and (3/4) nephrectomized ((3/4)nx) rats, up to 26 weeks after surgery. Male Wistar-Han rats (190-220 g; n = 49) were randomly assigned to (3/4)nx or Sham surgery. Two, 10 and 26 weeks after surgery, non-invasive blood pressure (BP) and left ventricular (LV) haemodynamics were performed, and urine and blood were collected for metabolic studies and plasma BNP determination. In addition, tissue samples from RC and RM were obtained for NPR-A and NPR-C quantification (RT-PCR and western blotting) as well as NPR-A immunodetection. In (3/4)nx rats, the progressive interstitial fibrosis and tubular atrophy were accompanied by a time-dependent increase of BP and impaired natriuretic response to volume expansion (VE). This was accompanied in (3/4)nx rats by an early and time-dependent elevation of BNP circulating levels that was not associated with cardiac dysfunction or increased myocardial BNP gene expression. In (3/4)nx rats, NPR-A expression in the remnant RM was consistently reduced at 2, 10 and 26 weeks, and this was accompanied by an increase in NPR-C expression in the remnant RC from (3/4)nx rats. BP elevation and compromised natriuretic response to VE in (3/4)nx rats is associated with increased circulating BNP levels in the absence of cardiac dysfunction. This is accompanied in (3/4)nx rats by both impaired NPR-A expression in the RM and upregulation of NPR-C in the RC suggesting a novel mechanism for NP resistance in CRI.

Supraventricular Tachycardia in Fetus: How Can We Treat ?

The normal fetal cardiac rhythm is characterized by a regular heart rate ranging between 100 and 160 -180 beats/min with a normal 1: 1 atrioventricular electromechanical relationship during each cardiac cycle. Fetal tachycardia occurring in approximately 0.5% of all pregnancies and it is an important cause of fetal morbidity and mortality. A fetal tachycardic heart is at risk for developing low cardiac output, hydrops and ultimately fetal death or significant neurological morbidity. Different conditions can play a role to determine the natural history of tachycardic fetus as gestational age, underlying pathophysiology of the arrhythmia, fetal heart rate, duration of the tachyarrhythmia, and presence or absence of cardiac dysfunction. Reliable diagnosis in utero of fetal arrhythmia is possible by ultrasound examination of the fetal heart. In fact pulsed wave Doppler guided by two-dimensional echocardiography provided important information on cardiac rhythm as it study the blood flow from different chambers. With the introduction of the latest myocardial deformation methodology, the fetal tachyarrhythmias can be diagnosed more accu notrately. Precise diagnosis of cardiac arrhythmias in the fetus is crucial for a managed therapeutic approach. The choice of management is correlated to many factors: gestational age, underlying pathophysiology of the arrhythmia, fetal heart rate, duration of the tachyarrhythmia, and presence or absence of cardiac dysfunction. A large review of fetal arrhythmias was been reported in our work.

Chronic Hypoxemia Increases Ventricular Brain Natriuretic Peptide Precursors in Neonatal Swine

Circulating levels of atrial natriuretic peptide and brain natriuretic peptide (BNP) are elevated in patients with cyanotic congenital heart disease and associated with the severity of ventricular dysfunction. We evaluated the effect of chronic hypoxemia on left ventricle pro-atrial natriuretic peptide and pro-BNP, the cytoplasmic precursors of the plasma hormones. Forty newborn piglets were randomized to placement of a pulmonary artery to left atrium shunt to create hypoxemia or sham thoracotomy. Animals were studied at 1 or 2 weeks after the procedure (four groups, n = 10 per group). Arterial oxygen tension and hematocrit were obtained. Left ventricular shortening fraction was measured by echocardiography. Left ventricular tissue was harvested and cytoplasm was extracted. Pro-BNP levels were determined by Western blot analysis. Pro-atrial natriuretic peptide levels were determined using enzyme-linked immunosorbent assay. Significant differences among treatment groups were observed for arterial oxygen tension (p < 0.001) and hematocrit (p < 0.001). Pairwise comparisons indicated lower arterial oxygen tension and higher hematocrit for hypoxemic piglets compared with control piglets at 1 and 2 weeks. Left ventricular shortening fraction was not decreased in the hypoxemic animals at any time (p = 0.638). Left ventricular pro-atrial natriuretic peptide decreased in hypoxemic piglets (p = 0.029), whereas left ventricular pro-BNP increased in hypoxemic piglets at 2 weeks (p = 0.002). Chronic hypoxemia alone, even in the absence of cardiac dysfunction, is sufficient to increase ventricular levels of pro-BNP. This finding may have implications for the interpretation of BNP levels in the clinical management of patients with cyanotic congenital heart disease.

Effect of Weight Loss following Bariatric Surgery on Myocardial Dispersion of Repolarization in Morbidly Obese Patients

Weight-stable obese subjects have an increased risk of arrhythmias and sudden death, even in the absence of cardiac dysfunction, and the risk of sudden cardiac death (SCD) with increasing weight is seen in both genders. The mechanism of unexplained deaths in obese patients is still unclear and may be related to ventricular repolarization abnormalities. The aim of this study is to determine the effect of severe obesity on spatial and transmural ventricular repolarization and to clarify the influence of bariatric surgery with a consequent substantial weight loss on arrhythmogenic substrate in the morbidly obese population. For the study, we enrolled 100 severely obese patients; 50 age-matched non-obese healthy subjects were also recruited as controls. All subjects underwent conventional 12-lead electrocardiography for analysis of spatial and transmural ventricular repolarization assessed by corrected QT dispersion (QTc-d), corrected JT dispersion (JTc-d) and transmural dispersion of repolarization, (TDR). All subjects underwent bariatric surgery and were resubmitted to electrocardiographic, biochemical and anthropometric examination 12 months postoperatively. Severely obese patients had greater values in QTc-d, JTc-d and TDR than the normal-weight controls. Bariatric surgery reduced significantly the QTc-d value, JTc-d value and TDR value. There was a significant correlation between decrease of heterogeneity of repolarization indexes (QTd, JTd and TDR) and bariatric surgery-induced weight loss. In severely obese patients, surgically-induced weight loss is associated with significant decrease in the heterogeneity of ventricular repolarization. The reduction of spatial (QTc-d, JTc-d) and transmural dispersion of repolarization (TDR) may be of clinical significance, by reducing the risk of potentially fatal arrhythmias in morbidly obese subjects.

Prognostic values of B-type natriuretic peptide in severe sepsis and septic shock*

To investigate the changes in B-type natriuretic peptide concentrations in patients with severe sepsis and septic shock and to investigate the value of B-type natriuretic peptide in predicting intensive care unit outcomes. Prospective observational study. General intensive care unit. Forty patients with severe sepsis or septic shock. None. B-type natriuretic peptide measurements and echocardiography were carried out daily for 10 consecutive days. In-hospital mortality and length of stay were recorded. The admission B-type natriuretic peptide concentrations were generally increased (747 +/- 860 pg/mL). B-type natriuretic peptide levels were elevated in patients with normal left ventricular systolic function (568 +/- 811 pg/mL), with sepsis-related reversible cardiac dysfunction (630 +/- 726 pg/mL), and with chronic cardiac dysfunction (1311 +/- 1097 pg/mL). There were no significance changes in B-type natriuretic peptide levels over the 10-day period. The daily B-type natriuretic peptide concentrations for the first 3 days neither predicted in-hospital mortality nor correlated with length of intensive care unit or hospital stay. B-type natriuretic peptide concentrations were increased in patients with severe sepsis or septic shock regardless of the presence or absence of cardiac dysfunction. Neither the B-type natriuretic peptide levels for the first 3 days nor the daily changes in B-type natriuretic peptide provided prognostic value for in-hospital mortality and length of stay in this mixed group of patients, which included patients with chronic cardiac dysfunction.

Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure

POINT-COUNTERPOINT COMMENTSIncreased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failureMary G. Garry, Scott A. Smith, and Jere H. MitchellMary G. Garry, Scott A. Smith, and Jere H. MitchellPublished Online:01 Jan 2007https://doi.org/10.1152/japplphysiol.01256.2006This is the final version - click for previous versionMoreSectionsPDF (26 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations The following letter is in response to the Point:Counterpoint series “Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure” that appears in this issue.To the Editor: There can be no more debate as to the validity of the skeletal muscle hypothesis. This peripheral paradigm revealed in the elegant studies of Piepoli and Coats (3) and based on the classic study of McCloskey and Mitchell (1) has set the stage for new insights into the mechanisms of abnormal cardiovascular responses to exercise in heart failure. Our current research confirms these findings as we are able to invoke exaggerations in the exercise pressor reflex by inducing a peripheral abnormality by ablating group IV afferent neurons in normal neonatal rat pups (6). When these animals reached adulthood we observed abnormal increases in mean arterial pressure and heart rate in response to exercise, yet these animals displayed normal left ventricular function. These data indicate that abnormal responses to exercise can be generated by peripheral abnormalities in primary afferent neurons in the absence of cardiac dysfunction. Middlekauff et al. (2) showed in humans and we (5) showed in rats that the mechanoreflex mediates the abnormal responses to exercise in heart failure and we (5) showed the same in animals lacking group IV afferent neurons. Additionally, we (5) demonstrated that the metaboreflex is blunted in these rats just as it is in rats in heart failure. These latter data are consistent with the observations of Sinoway and colleagues (4) in both humans and rats. We hypothesize that the blunting of the metaboreflex that occurs in heart failure initiates a series of events that results in the overactivity of the mechanoreflex.REFERENCES1 McCloskey DI, Mitchell JH. Reflex cardiovascular and respiratory responses originating in exercising muscle. J Physiol 224: 173–186, 1972.Crossref | PubMed | ISI | Google Scholar2 Middlekauff HR, Nitzsche EU, Hoh CK, Hamilton MA, Fonarow GC, Hage A, Moriguchi JD. Exaggerated muscle mechanoreflex control of reflex renal vascoconstriction in heart failure. J Appl Physiol 90: 1714–1719, 2001.Link | ISI | Google Scholar3 Piepoli M, Ponikowski P, Clark AL, Banasiak W, Capucci A, Coats AJ. A neural link to explain the “muscle hypothesis” of exercise intolerance in chronic heart failure. Am Heart J 137: 1050–1056, 1999.Crossref | PubMed | ISI | Google Scholar4 Sinoway LI, Li J. A perspective on the muscle reflex: implications for congestive heart failure. J Appl Physiol 99: 5–22, 2005.Link | ISI | Google Scholar5 Smith SA, Mitchell JH, Naseem RH, Garry MG. Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure. Circulation 112: 2293–2300, 2005Crossref | PubMed | ISI | Google Scholar6 Smith SA, Williams MA, Mitchell JH, Mammen PP, Garry MG. The capsaicin-sensitive afferent neuron in skeletal muscle is abnormal in heart failure. Circulation 111: 2056–2065, 2005.Crossref | PubMed | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByA murine model of the exercise pressor reflex12 June 2020 | The Journal of Physiology, Vol. 598, No. 15 More from this issue > Volume 102Issue 1January 2007Pages 502-502 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01256.2006PubMed17095629History Published online 1 January 2007 Published in print 1 January 2007 Metrics

Primary adhalinopathy (alpha-sarcoglycanopathy): clinical, pathologic, and genetic correlation in 20 patients with autosomal recessive muscular dystrophy.

Primary adhalin (or alpha-sarcoglycan) deficiency due to a defect of the adhalin gene localized on chromosome 17q21 causes an autosomal recessive myopathy. We evaluated 20 patients from 15 families (12 from Europe and three from North Africa) with a primary adhalin deficiency with two objectives: characterization of the clinical phenotype and analysis of the correlation with the level of adhalin expression and the type of gene mutation. Age at onset and severity of the myopathy were heterogeneous: six patients were wheel-chair bound before 15 years of age, whereas five other patients had mild disease with preserved ambulation in adulthood. The clinical pattern was similar in all the patients with symmetric characteristic involvement of trunk and limb muscles, calf hypertrophy, and absence of cardiac dysfunction. Immunofluorescence and immunoblot studies of muscle biopsy specimens showed a large variation in the expression of adhalin. The degree of adhalin deficiency was fairly correlated with the clinical severity. There were 15 different mutations (10 missense, five null). Double null mutations (three patients) were associated with severe myopathy, but in the other cases (null/missense and double missense) there was a large variation in the severity of the disease.

Endomyocardial biopsy findings in pediatric patients with post myocarditic state.

Endomyocardial biopsy was performed on eight children 5 to 12 years old, who were in post myocarditic state. They were evaluated within 2 to 25 months (mean lyr and 1 m) after the onset of the symptoms. Two of the patients developed heart failure and six patients developed other cardiac manifestations such as syncope, palpitation or ECG abnormalities at onset. Definite elevation of viral antibody titer was observed in four patients. Radionuclide angiography was also performed in all eight patients. An abnormal perfusion area was observed in six patients as a focal hypoperfusion area by T1-201 myocardial imaging. Ejection fraction was examined by Tc-99m-HSA gated equilibrium ventriculography. LVEF was reduced in 3 patients and RVEF was reduced in 2 patients. Judging from the histopathological findings, these patients were divided into three categories: chronic or smoldering myocarditis (3 patients); healing or healed myocarditis (4 patients); and post myocarditic hypertrophy (1 patient). Measurement of left ventricular function was obtained by cardiac catheterization and left ventriculography (LVG), which revealed some abnormal findings such as increased left ventricular mass index, increased left ventricular end diastolic volume index (LVEDVI) and reduced left ventricular ejection fraction (LVEF). Therefore, endomyocardial biopsy findings of pediatric patients in a post myocarditic state reveal certain histopathological abnormalities even in the long-term follow-up period in the absence of cardiac dysfunction.