Ventricle In Cardiomyopathy Research Articles

Marked differences in ICD therapy frequencies between phenotypes

Abstract Background Implantable cardioverter defibrillators (ICD) are implanted due to a broad range of cardiac conditions according to guidelines. Purpose The aim of this study was to compare the distribution of ICD therapies across different cardiac diseases. Methods In this descriptive study, we included patients from Eastern Denmark with an ICD implanted up until November 2021. Data was obtained from the national ICD registry and the diagnosis leading to implantation of the ICD was registered. ICD interrogations and number of episodes of appropriate ICD therapies (shock/anti-tachycardia pacing (ATP)) were obtained. End of follow-up was November 8, 2021 or date of death or heart transplantation. Cumulated numbers of therapies were calculated for each patient during the follow-up period (shock/ATP therapies per 1,000 patients per year). Results Data on 3,068 patients (median (IQR) age at implantation 65 years (56-72)) across 10 cardiac disorders was obtained (Figure). A total of 1,403 patients had the ICD implanted as primary prophylaxis and 1,554 as secondary prophylaxis and in 111 patients it was unclear. Mean follow-up time of 595 years per diagnostic subgroup (210-12,911 years). The median (IQR) shock/ATP rate per 1,000 patients per year was 1.47 (0.70-2.62). The numerically highest shock/ATP rate of 28.9 therapies per 1,000 patients per year was seen in patients with arrhythmogenic right ventricle cardiomyopathy and the lowest shock/ATP rate of 0.05 therapies per 1,000 patients per year was seen in patients with ischemic heart disease. In patients with ischemic heart disease, the shock/ATP rate per year was 0.06 in patients with an ICD implanted as primary prophylactic and 0.15 in patients with an ICD as secondary prophylactic. Conclusion The frequency of ICD shock/ATP therapy varies several-fold between cardiac disorders, with the highest rate in patient with arrhythmogenic right ventricle cardiomyopathy and the lowest rate in the major group of patients, i.e. patients with ischemic heart disease. These findings may indicate a need for adjustments of patient selection for ICD implantation.

The pivotal role of ECG in cardiomyopathies.

Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Recent technological advances in cardiovascular imaging offer an opportunity for deep phenotypic and etiological definition. Electrocardiogram (ECG) is the first-line diagnostic tool in the evaluation of both asymptomatic and symptomatic individuals. Some electrocardiographic signs are pathognomonic or fall within validated diagnostic criteria of individual cardiomyopathy such as the inverted T waves in right precordial leads (V1-V3) or beyond in individuals with complete pubertal development in the absence of complete right bundle branch block for the diagnosis of arrhythmogenic cardiomyopathy of the right ventricle (ARVC) or the presence of low voltages typically seen in more than 60% of patients with amyloidosis. Most other electrocardiographic findings such as the presence of depolarization changes including QRS fragmentation, the presence of epsilon wave, the presence of reduced or increased voltages as well as alterations in the repolarization phase including the negative T waves in the lateral leads, or the profound inversion of the T waves or downsloping of the ST tract are more non-specific signs which can however raise the clinical suspicion of cardiomyopathy in order to initiate a diagnostic procedure especially using imaging techniques for diagnostic confirmation. Such electrocardiographic alterations not only have a counterpart in imaging investigations such as evidence of late gadolinium enhancement on magnetic resonance imaging, but may also have an important prognostic value once a definite diagnosis has been made. In addition, the presence of electrical stimulus conduction disturbances or advanced atrioventricular blocks that can be seen especially in conditions such as cardiac amyloidosis or sarcoidosis, or the presence of left bundle branch block or posterior fascicular block in dilated or arrhythmogenic left ventricular cardiomyopathies are recognized as a possible expression of advanced pathology. Similarly, the presence of ventricular arrhythmias with typical patterns such as non-sustained or sustained ventricular tachycardia of LBBB morphology in ARVC or non-sustained or sustained ventricular tachycardia with an RBBB morphology (excluding the "fascicular pattern") in arrhythmogenic left ventricle cardiomyopathy could have a significant impact on the course of each disease. It is therefore clear that a learned and careful interpretation of ECG features can raise suspicion of the presence of a cardiomyopathy, identify diagnostic "red flags" useful for orienting the diagnosis toward specific forms, and provide useful tools for risk stratification. The purpose of this review is to emphasize the important role of the ECG in the diagnostic workup, describing the main ECG findings of different cardiomyopathies.

Development of health-based exposure limits for radiofrequency radiation from wireless devices using a benchmark dose approach

BackgroundEpidemiological studies and research on laboratory animals link radiofrequency radiation (RFR) with impacts on the heart, brain, and other organs. Data from the large-scale animal studies conducted by the U.S. National Toxicology Program (NTP) and the Ramazzini Institute support the need for updated health-based guidelines for general population RFR exposure.ObjectivesThe development of RFR exposure limits expressed in whole-body Specific Absorption Rate (SAR), a metric of RFR energy absorbed by biological tissues.MethodsUsing frequentist and Bayesian averaging modeling of non-neoplastic lesion incidence data from the NTP study, we calculated the benchmark doses (BMD) that elicited a 10% response above background (BMD10) and the lower confidence limits on the BMD at 10% extra risk (BMDL10). Incidence data for individual neoplasms and combined tumor incidence were modeled for 5% and 10% response above background.ResultsCardiomyopathy and increased risk of neoplasms in male rats were the most sensitive health outcomes following RFR exposures at 900 MHz frequency with Code Division Multiple Access (CDMA) and Global System for Mobile Communications (GSM) modulations. BMDL10 for all sites cardiomyopathy in male rats following 19 weeks of exposure, calculated with Bayesian model averaging, corresponded to 0.27–0.42 W/kg whole-body SAR for CDMA and 0.20–0.29 W/kg for GSM modulation. BMDL10 for right ventricle cardiomyopathy in female rats following 2 years of exposure corresponded to 2.7–5.16 W/kg whole-body SAR for CDMA and 1.91–2.18 W/kg for GSM modulation. For multi-site tumor modeling using the multistage cancer model with a 5% extra risk, BMDL5 in male rats corresponded to 0.31 W/kg for CDMA and 0.21 W/kg for GSM modulation.ConclusionBMDL10 range of 0.2—0.4 W/kg for all sites cardiomyopathy in male rats was selected as a point of departure. Applying two ten-fold safety factors for interspecies and intraspecies variability, we derived a whole-body SAR limit of 2 to 4 mW/kg, an exposure level that is 20–40-fold lower than the legally permissible level of 0.08 W/kg for whole-body SAR under the current U.S. regulations. Use of an additional ten-fold children’s health safety factor points to a whole-body SAR limit of 0.2–0.4 mW/kg for young children.

Actionable secondary findings in arrhythmogenic right ventricle cardiomyopathy genes: impact and challenge of genetic counseling.

Comprehensive genetic analysis yields in a higher diagnostic rate but also in a higher number of secondary findings (SF). American College of Medical Genetics and Genomics (ACMG) published a list of 59 actionable genes for which disease causing sequence variants are recommended to be reported as SF including 27 genes linked to inherited cardiovascular disease (CVD) such as arrhythmia syndromes, cardiomyopathies and vascular and connective tissue disorders. One of the selected conditions represented in the actionable gene list is the arrhythmogenic right ventricle cardiomyopathy (ARVC), an inherited heart muscle disease with a particularly high risk of sudden cardiac death (SCD). Since clinical symptoms are frequently absent before SCD, a genetic finding is a promising option for early diagnosis and possible intervention. However, the variant interpretation and the decision to return a SF is still challenging. To determine the frequency of medically actionable SF linked to CVD we analyzed data of 6,605 individuals who underwent high throughput sequencing for noncardiac diagnostic requests. In particular, we critically assessed and classified the variants in the ARVC genes: DSC2, DSG2, DSP, PKP2 and TMEM43 and compared our findings with the population-based genome Aggregation Database (gnomAD) and ARVC-afflicted individuals listed in ClinVar and ARVC database. 1% (69/6,605) of tested individuals carried pathogenic SF in one of the 27 genes linked to CVD, of them 13 individuals (0.2%) carried a pathogenic SF in a ARVC gene. Overall, 582 rare variants were identified in all five ARVC genes, 96% of the variants were missense variants and 4% putative LoF variants (pLoF): frameshift, start/stop-gain/loss, splice-site. Finally, we selected 13 of the 24 pLoF variants as pathogenic SF by careful data interpretation. Since SF in actionable ARVC genes can allow early detection and prevention of disease and SCD, detected variant must undergo rigorous clinical and laboratory evaluation before it can be described as pathogenic and returned to patients. Returning a SF to a patient should be interdisciplinary, it needs genetic counselling and clinicians experienced in inherited heart disease.

Abstract 13664: Membrane Stiffness as a Function of Plakophilin-2 Expression: Implications to Arrhythmogenic Right Ventricular Cardiomyopathy

Mutations in PKP2 , the gene coding for the desmosomal protein Plakophilin-2 (PKP2), can lead to an inheritable cardiac disease called Arrhythmogenic Right Ventricle Cardiomyopathy (ARVC). Various studies investigated the molecular and electrical properties of cardiomyocytes (CMs) with PKP2 deficiency. However, systematic studies on the mechanical properties of PKP2-deficient CMs, and their relation to the cardiomyopathic phenotype, are lacking. We studied the relation between PKP2 expression, membrane transverse Young’s modulus (tYM; a surrogate measure of membrane stiffness), and their correlation with tubulin expression and with substrate stiffness. Left and right ventricular (LV, RV) CMs were isolated from murine hearts control (ctrl), or with a cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 (PKP2cKO). Three time points were studied: 14, 15 and 21 days post-tamoxifen injection (dpi). The phenotypes at these time points correspond to three disease stages: concealed, arrhythmogenic and cardiomyopathy of RV predominance, respectively. tYM was evaluated by mechanoSICM. Tubulin was visualized by confocal microscopy. tYM in LV myocytes from control hearts showed a tendency toward higher values when compared to RV myocytes (LV 2.9±0.2 kPa vs RV 2.6±0.2 kPa, n=53-59). At 14 dpi, LV and RV PKP2cKO CMs were softer than ctrl (LV 2.1±0.1 kPa, RV 2.1±0.1 kPa vs ctrl, n=30-59). The trend reversed a day later and by 21 dpi there was a clear increase in tYM, particularly in PKP2cKO RV myocytes (LV 4.5±0.3 kPa, RV 4.8±0.6 kPa vs ctrl, n=44-59). Z-groove index, a parameter of membrane organization, decreased in PKP2cKO CMs. Increased tYM at 21 dpi corresponded to upregulation of α-tubulin and particularly, acetylated tubulin, which was reduced at 14dpi but went up in 21dpi. We also observed an inverse correlation between membrane tYM, and substrate stiffness. We conclude that loss of PKP2 expression affects, in a disease stage-specific manner, CM mechanical properties and the MT network organization. Whether these effects are correlative or one is consequence of the other, remains to be determined. We speculate that changes in membrane mechanics at the single cell level are a component of mechanical dysfunction in hearts affected with ARVC.

Loss of SORBS2 in Cardiomyocytes Leads to Dilated Left Ventricle Cardiomyopathy in Mice

Through rigorous bioinformatic and wet‐lab investigations, we identified SORBS2 as a cardiac‐enriched gene that is consistently upregulated at mRNA and protein levels across diverse mouse models of heart failure (HF; genetic, ischemic, pressure‐overload) and in failing human hearts (ischemic, idiopathic). Significant reduction in SORBS2 protein levels are also found in aged heart. SORBS2 is among a family of adaptor proteins (SORBS1‐3) involved in cell adhesion and cytoskeletal organization; SORBS proteins localize to myocyte z‐discs and aid in aligning sarcomere and mitochondrial networks (Loveless et al. 2017 MBC). Global SORBS2 knockout mice display early death (100% at 4–6 months), potentially due to cardiac arrhythmia and right ventricle (RV) cardiomyopathy (Ding et al. 2019 BioRxiv). Beyond this, the role of SORBS2 in cardiomyocyte biology remains largely untested. We created a cardiomyocyte‐specific knockout of SORBS2 (SORBS2‐cKO) via MYH6‐CRE transgenic mice bred to floxed‐SORBS2 mice. To delete SORBS2 postnatally and separate the role of SORBS2 in adult cardiac function from development, floxed‐SORBS2 mice were also injected at 3 weeks of age with AAV2/9‐CRE virus. Heart function was measured from 3 months thru one year of age. Contrary to the work of Ding, et al., we report here that neither constitutive nor inducible cardiomyocyte‐restricted SORBS2 knockout leads to severe arrhythmias, RV dysfunction, or early death in mice. Instead, SORBS2‐cKO mice develop aging‐related left ventricle (LV) cardiomyopathy starting with LV wall motion abnormalities at ~ 8 months‐old, progressing to ~50% reduced LVEF and 30% increased HW/BW by 10 months‐old, and dilating with heart failure by 12 months (~400% increase LVEDV), with no detectable change to RV structure/function. Surface EKG recordings in SORBS2‐cKO mice show obvious conduction deficiencies including bifid P‐wave, prolonged QRS, and bundle branch block, starting at 3 months‐age and persisting through life. Notably, no mice showed irregular R‐R intervals, spontaneous atrial fibrillation or ventricular tachycardia. While exploring the mechanism of SORBS2 loss leading to conduction defects, we did not find reduced gap junction protein GJA1 levels in SORBS2‐cKO mouse hearts. This is interesting given that Ding, et al., reported a 90% decrease in GJA1 protein levels in global SORBS2‐KO mouse hearts. Consistent with prior literature, our bioinformatic analyses show a strong association for SORBS2 with cytoskeletal proteins and also point to new potential connections to cardiac signaling receptors/channels including SCN5A. Electrophysiology studies were conducted in isolated neonatal rat cardiomyocytes with siRNA‐mediated knockdown of SORBS2; however, no changes in SCN5A current properties were found. Altogether, these results highlight the importance of SORBS2 to cardiomyocyte biology likely through its primary role as a cytoskeletal adapter. Necessary, ongoing work will continue to precisely define how loss of SORBS2 in cardiomyocytes leads to dilated cardiomyopathy, assessing sarcomere organization, excitation‐contraction coupling, and cardiomyocyte force mechanics.Support or Funding InformationThis work was funded by 19POST34380640 to JMM, HL137272 to DSM, HL147545 to BL, and HL144717 and HL148796 to RLB.

Prevalence of complete and incomplete right bundle branch block in young athletes: A local study

Sparse data exists to characterize the disease prevalence in athletic patients with complete and incomplete right bundle branch block: (CRBBB) and (IRBBB) respectively. We sought to determine this prevalence in a local sport medical centre. We analysed ECG of athletes on-going a routine and mandatory medical examination in our local sport medical centre. All participants had 2 months of regular activity for at least 4 hours a week (h/w) prior to inclusion. Median follow-up period was 18 months. Five hundred and forty-eight athletes were enrolled in the study. History, physical examination and a 12 lead standard ECG was performed for all the participants. Demographic and baseline information for the study participants are exposed in Table 1. BBBD pattern was found in 77 (14%) participants, only one had CRBBB. IRBBB prevalence was 13.86% and CRBBB 0.1%. The athlete with CRBBB had not associated electrocardiographic anomalies suggesting Brugada syndrome or arrythmogenic right ventricle cardiomyopathy. He had a normal Treadmill stress test. His echocardiogram showed mild right ventricle dilatation and was allowed to continue his activity. No events were noticed in this population subset. RBBB is not rare in athlete's community. IRBBB is more common and considered benign. CRBBB is more rare and needs further work-up.

The non-compact left ventricle cardiomyopathy: clinical features and diagnostic capabilities

The non-compact left ventricular cardiomyopathy (NCLVC) refers to the non-classified cardiomyopathies. Its cause is not completely clear. NCLVC is characterized by an increased trabecular with the formation of deep intertrabecular crypts. It can exist either in isolated form or in combination with other congenital diseases. The clinical features of NCLVC are different: asymptomatic forms are identified as well as forms with the progressive course of the disease, with heart failure, angina, thromboembolic complications, and ventricular arrhythmias. In some cases, the disease starts with the sudden cardiac death. The sudden decompensation of NCLVC also could arise due to the development of acute myocarditis

Noncompaction cardiomyopathy

Noncompaction cardiomyopathy (NCCM) is a genetic myocardial disorder, which is characterized by a two-layered ventricle wall with a thin compact outer layer and a noncompacted inner layer, with prominent trabeculations and deep intratrabecular recesses communicating with the ventricle cavity without any contact to the coronary system. Before the initial description as isolated left ventricle cardiomyopathy (ILVCN) in 1984 by Engberding and Bender, the morphological characteristics had been described only in association with other congenital cardiac disorders, such as atresia of the semilunar valves. The disease usually involves the myocardium of the left ventricle but involvement of the right ventricular has recently been shown. Due to delayed diagnosis and therapy, in advanced stages NCCM can result in heart failure. Life-threatening complications, such as malignant arrhythmia with sudden cardiac death and embolic events have been observed in patients with NCCM. A multimodal investigation including echocardiography and cardiac magnet resonance tomography (CMR) as well as a focused analysis of symptoms can allow a valid diagnosis.

Advantages of early replacement therapy for mucopolysaccharidosis type VI: echocardiographic follow-up of siblings

Mucopolysaccharidosis type VI (Marateaux-Lamy syndrome) is an autosomal recessive disorder caused by deficient activity of the enzyme N-acetylgalactosamine-4-sulphatase (arylsulphatase B). Cytoplasmic vacuoles full of dermatan sulphate are observed in endothelial cells, myocyte, and fibroblasts, compromising the function of cardiovascular structures and contributing significantly towards morbidity and mortality. The primary objective of this study was to assess the advantages of early replacement therapy with recombinant human arylsulphatase B through the echocardiographic follow-up of sisters who started treatment at quite different ages: one at 9 years and the other at 1 year and 7 months. The older sibling showed striking mitral and aortic valve compromise when she was only 2 years old and finally needed cardiac surgery at the age of 8, even before starting enzyme replacement. Differently, the younger one has developed only mild mitral and aortic lesions throughout the follow-up period of 3 years. The two siblings had left ventricle cardiomyopathy, but partial reverse remodelling was induced by enzyme replacement therapy in both cases. The younger sibling has never received any cardiovascular drugs, whereas the older one has been using β-blockers and diuretics in addition to enzyme therapy to cope with heart failure. Comparing the outcomes of these two sisters with a very aggressive phenotype of mucopolysaccharidosis type VI, the conclusion was that early onset of therapy may slow down the disease progression and prevent severe cardiac lesions to be established. Moreover, patients' compliance is essential for the success of treatment, as sequential echocardiographic evaluation demonstrated worsening of some cardiac lesions whenever infusions were missed.

Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy

The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart.

Sudden cardiac death secondary to demonstrated reperfusion ventricular fibrillation in a woman with Takotsubo cardiomyopathy

Takotsubo cardiomyopathy is a left ventricle cardiomyopathy characterized by a reversible dyskinesia responsible for the typical apical ballooning aspect. The disease is considered benignant with a full recovery within a few weeks. We present the case of a 52-year-old woman who presented with angina diagnosed with Takotsubo cardiomyopathy on the basis of both noninvasive (electrocardiography, echocardiography) and invasive (angiography) exams. At discharge, a Holter monitor was fitted to the patient. During the recording the patient faced sudden cardiac death. The analysis of the Holter traces allowed some speculations on the mechanism of this unexpected arrhythmic death. The cause of the fatal ventricular fibrillation appears to be the fast reperfusion following a short occlusion of an epicardial coronary artery. This case highlights the epicardial vasospasm as an important pathogenic mechanism of the syndrome and the possible usefulness of diagnostic tests able to elicit the spasm susceptibility and guide a more targeted pharmacological therapy. Some considerations are also possible on the cellular processes linking the rapid reperfusion and the arrhythmias onset.

Pathological study of unexpected sudden death clustered in family or village in Yunnan province: report of 29 cases of autopsy

To investigate the pathological features and causes of sudden death clustered in family or village in Yunnan province so as to provide the morphological basis for exploring its etiology and medical intervention. Autopsy was performed on 29 cases of clustered in family or village in Yunnan province during the period 1991-2006, 16 males and 13 females, aged 32 (8-69), accounting for 10.2% of whole sudden unexpected deaths occurring in the same period. The heart, lung, liver, spleen, brain, kidney, intestinal tract, and other organs were examined macroscopically and histologically, including a study of cardiac conduction system in 5 cases. Pathological diagnosis of myocarditis was based on the Dallas Criteria and World Heart Federation's consensus while the histological evaluation of Keshan disease referred the China national guideline for pathological diagnosis of Keshan disease. Based on the main pathological changes and the causes of death, these cases were classified into seven groups (group A-G). Group A comprised 11 cases (38%) with lymphocytic myocarditis accompanied with focal myocardial necrosis or degeneration. Group B comprised 3 cases (10%) with neutrophil myocarditis accompanied with focal myocytolysis or coagulation necrosis. Group C comprised 4 cases (14%) with arrhythmogenic right ventricle cardiomyopathy in which fatty infiltration of myocardium was the only pathological finding. Group D comprised 2 cases (7%) with ischemic heart disease in which fresh or old foci of myocardial infarction were found but coronary stenosis was shown only in one case. Group E comprised 2 cases (7%) with left ventricle hypertrophy and obstructive muscle bundle in the outflow of left ventricle. Group F comprised 2 cases (7%) with allergic bronchitis or chronic bronchitis and pulmonary emphysema. Group G comprised the remaining 5 cases (17%) without any pathological finding that could explain sudden death. No cases suffered with Keshan disease and dilated cardiomyopathy. Focal but not diffuse inflammatory infiltration was the prominent histological feature of myocarditis in Yunnan cases. Among the five cases with histological examination of cardiac conduction system, 2 cases were detected to suffer from acute hemorrhage in His bundle and its left branching site, and the atrioventricular node of 1 case was involved. Different pathological changes coexisted in 4 pairs of family members as a cluster of sudden deaths. 3 of 4 first deaths had focal myocarditis and the other one had chronic infection. But 3 secondary deaths had myocardial ischemia and the other one had arrhythmogenic right ventricle cardiomyopathy. Pulmonary edema, acute respiratory infection and congestive or ischemic liver necrosis were found in some cases simultaneously. The pathological changes of the cases of clustered sudden death in Yunnan province are various, such as myocarditis, myocardial dysplasia and the other lethal heart-lung disorders. No case of Keshan disease has been found. Arrhythmogenic right ventricle cardiomyopathy and other foundational heart diseases might act as a background. It is very hard to contribute only one etiological factor to the clustering of sudden death in Yunnan. It was most likely that multiple factors cluster and trigger an outbreak of death in a definite time and space.

Cardiac nuclear hormone receptor mRNA in heart failure in man.

Eight donor hearts and six explanted hearts due to dilated cardiomyopathy, normal skeletal muscle and liver were analysed. Glucocorticoid receptor (GR) and thyroid hormone receptor (T3R) isoforms beta 1, beta 2, alpha 1 and alpha 2 mRNA abundance were determined by solution hybridization. Both GR and T3R receptor mRNA isoforms were lower in the myocardium as compared to skeletal muscle and in particular to liver. GR mRNA abundance was higher than that of any T3R isoform while the sum of ligand-binding isoforms (beta 1, beta 2 and alpha 1) were similar in the myocardium and in skeletal muscle as opposed to the liver where GR mRNA was higher. GR mRNA abundance was similar in right and left ventricles from donor hearts and in cardiomyopathy. T3R beta 1 showed higher levels in the right ventricle with higher levels in cardiomyopathy as compared to donor heart. T3R isoform alpha 1 and especially the alpha 1/alpha 2 ratio were lower in left ventricle in cardiomyopathy compared to donor hearts. In conclusion, GR and T3R isoforms mRNA abundance are low in the human myocardium. In the failing myocardium GR and T3R beta 2 and alpha 2 show no signs of reactivity while T3R beta 1 and alpha 1 mRNA adapt.