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Autoantibodies in congenital heart blockKlauninger, Robert. January 2009 (has links)
Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2009.
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Complete Heart Block in Association With Dengue Hemorrhagic FeverVirk, Hafeez Ul Hassan, Inayat, Faisal, Ur Rahman, Zia 01 November 2016 (has links)
Dengue virus infection affects the heart structurally and functionally. Clinical manifestations of cardiac complications secondary to dengue virus infection vary from self-limiting arrhythmias to severe myocardial infarction, leading to hypotension, pulmonary edema, and cardiogenic shock. However, we report a case of dengue hemorrhagic fever (DHF) complicated by a complete heart block. A female with DHF due to dengue virus serotype 2, presented to the emergency department with fever, headache, rash, and fatigue followed by an episode of syncope. She was found to have a third-degree atrioventricular block, with pulseless polymorphic ventricular tachycardia. Patient was resuscitated and a temporary trans-venous pacemaker was placed. She reverted back to normal sinus rhythm after 4 days of syncope and was subsequently discharged from the hospital after complete resolution of symptoms, without the need for a permanent pacemaker. Physicians are warranted to have high index of suspicion for dengue virus infection as an etiology in patients with acute cardiovascular compromise, especially in tropical areas.
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The role of Ro52 autoantibodies in congenital heart block /Salomonsson, Stina, January 2004 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 10 uppsatser.
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Molecular characterization of the Ro52 autoantigen and its disease related epitopes /Ottosson, Lars, January 2005 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.
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Prenatal Heart Block Screening in Mothers With SSA/SSB Auto-antibodies: Targeted Screening Protocol is a Cost-Effective StrategyEvers, Patrick D., M.D. 09 July 2019 (has links)
No description available.
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Distrofia Muscular de Duchenne: análise eletrocardiográfica de 131 casos / Duchenne Muscular Dystrophy: electrocardiographic analysis of 131 patientsSantos, Maria Auxiliadora Bonfim [UNIFESP] 22 February 2011 (has links) (PDF)
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Publico-12588b.pdf: 1611234 bytes, checksum: 5bb4cedebc746bef2f551f891a283a74 (MD5) / Fundamento: É conhecido o envolvimento cardíaco em pacientes com distrofia muscular de Duchenne (DMD). O eletrocardiograma (ECG) apresenta algumas alterações típicas na DMD, fato que o torna um exame útil no diagnóstico da lesão cardíaca nessa patologia. Objetivo: Avaliar as alterações eletrocardiográficas em pacientes portadores de DMD, correlacionando-as com a idade da população estudada. Métodos: Foram analisados os ECG de 131 pacientes com diagnóstico do DMD. Avaliaram-se diversas variáveis eletrocardiográficas, sendo os pacientes separados em dois grupos: aqueles com e sem alterações, por variável estudada. Fezse a correlação desses dois grupos com a idade dos pacientes. Foram utilizados os critérios de Garson para estabelecer os parâmetros eletrocardiográficos de normalidade. Resultados: O ECG estava anormal em 78,6% dos pacientes. Todos apresentavam ritmo sinusal. Foram os seguintes os percentuais encontrados para as principais variáveis estudadas: PR curto= 18,3%, ondas R anormais em V1 = 29,7%, onda Q anormais em V6 = 21,3%, alterações da repolarização ventricular = 54,9%, ondas QS anormais em paredes inferior e/ou lateral alta = 37,4%, distúrbios de condução pelo ramo direito = 55,7%, intervalo QTc prolongado = 35,8% e alargamento do QRS = 23,6%. O teste t, não pareado, foi utilizado para se estabelecer a correlação da idade com as variáveis eletrocardiográficas estudadas nos dois grupos e, apenas a variável alteração da repolarização mostrou diferença estatisticamente significante. Conclusão: As alterações eletrocardiográficas na DMD são frequentes, revelando comprometimento cardíaco precoce. Apenas a variável alteração da repolarização ventricular foi mais frequente, porém em faixa etária menor (p<0,05). / TEDE / BV UNIFESP: Teses e dissertações
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The search for the PFHBI gene : refining the target area and identification and analysis of candidate gene transcriptsArieff, Zainunisha 12 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Progressive familial heart block I (PFHBI) is an inherited autosomal dominant cardiac
conduction disorder which segregates in a large South African (SA) pedigree, two
smaller SA families and a Lebanese family. It specifically affects conduction in the
ventricles and is of unknown cause. Clinically, PFHBI is detected on electrocardiogram
(ECG) by evidence of bundle-branch disease, i.e., as right bundle branch block, left
anterior or posterior hemiblock, or complete heart block with broad QRS complexes. The
PFHBI-causative gene was mapped to a lOcM region on chromosome 19ql3.3 using
linkage analysis, and the locus was subsequently reduced to 7cM by genetic fine
mapping.
The present study involved a multi-strategy approach to search for the PFHBI gene. The
objectives were the further reduction of the PFHBI locus by genetic fine mapping using
published and novel markers, searching for short gene transcripts from publicly available
databases and the generation of an integrated map of the locus to which genes were
mapped. Prioritised genes were screened for PFHBI-causing mutations and, in addition,
the PFHBI locus was searched for the presence of a G protein-encoding gene (PI 15-
RhoGEF), a connexin (Cx) gene and any genes containing a CTG repeat expansion motif,
since these genes are plausible PFHBI candidate genes.
Genotyping and fine genetic mapping using known and novel polymorphic dinucleotide
(CA)n and novel tetranucleotide (A3G)n repeat markers across the PFHBI locus were
performed. Publicly available databases, such as LLNL (Livermore, USA), and
GENEMAP (NCBI) were searched for ESTs which, in turn, were extended using
clustering programmes, such as UNIGENE (NCBI) and STACK (SANBI), and the
resulting consensus sequences were subsequently BLAST-searched against the protein
databases. Using the available data, an integrated physical and genetic map of the PFHBI
locus was generated and, as the HGP progressed, a number of novel genes were placed
thereon. Subsequently, genes were prioritised on the basis of position, function and expression profile.
Genetic fine mapping reduced the PFHBI locus from 7cM to 4cM. The EST approach
yielded 38 ESTs, of which 24 ESTs matched proteins, such as activating transcription
factor 5 (ATF5), actin-binding protein (KPTN) and zinc finger protein 473 (ZFP473)
(May 2003). All the map data generated experimentally and computationally were placed
on the PFHBI map. The PI 15-RhoGEF was excluded as a PFHBI candidate gene and
although homologous sequences to connexin 37 (Cx37) was located on both chromosome
19 radiation hybrid clones (RHG12 and ORIM-7), it was not identified on the DNA
clones spanning the PFHBI locus. No evidence of an expansion of a CTG repeat motif
sequence in PFHBI-affected individuals was found. Five highly prioritised candidate
genes, namely, 5CZ2-associated X protein (BAX), potassium voltage-gated channel
Shaker-related subfamily member 7 (KCNA7’), potassium inwardly-rectifying channel,
subfamily J, member 14 (KIR2.4), lin-7 homolog B {LIN-7B) and glycogen synthase 1
(GSYI) were selected for mutation screening. No disease associated mutations were
identified in the exonic and flanking intronic regions of these genes.
In summary, this study reduced the PFHBI locus substantially and generated a detailed
map of the region. A number of attractive candidate genes were excluded from causing
PFHBI; however, several plausible candidate genes are still present at this gene-rich
locus and remain to be screened. Identifying the PFHBI-causative gene and associated
mutation will provide a platform for further studies to understand the pathophysiology,
not only of PFHBI, but also of other more commonly occurring conduction disturbances. / AFRIKAANSE OPSOMMING: Progressiewe familiele hartblok I (PFHBI) is ‘n autosomaal dominant oorerflike kardiale
geleidingstoomis wat in ‘n groot Suid-Afrikaanse (SA) familie, twee kleiner SA families en ‘n
Lebanese familie segregeer. Dit affekteer hoofsaaklik die geleiding in die ventrikels en die oorsaak
daarvan is onbekend. Klinies word PFHBI op elektrokardiogram (EKG) geidentifiseer as a
bondeltak-siekte, naamlik, as regter bondeltakblok, linker anterior of posterior hemiblok, of
volledige hartblok met wye QRS komplekse. Die PFHBI-veroorsakende geen is voorheen deur
koppelingsanalise tot ‘n lOcM gebied op chromosoom 19ql3.3 gekarteer, en daaropvolgens is die
lokus verklein tot 7cM deur genetiese fyn kartering.
Die huidige studie behels ‘n veelvuldige-strategie benadering in die soektog na die PFHBI geen.
Die doel van die studie was die verdere verkleining van die PFHBI lokus deur gebruik te maak van
beide gepubliseerde en nuwe genetiese merkers, die identifisering van kort geentranskripte (ESTs)
uit publieke databanke en die generasie van ‘n geintegreerde kaart van die lokus. Geprioritiseerde
gene is geanaliseer vir die PFHBI-veroorsakende mutasie en, daarby, is die PFHBI lokus deursoek
vir die teenwoordigheid van ‘n G proteien-enkodeeringsgeen (PIJ5-RhoGEF), ‘n konneksien (Kx)
geen en enige gene wat ‘n uitgebreide CTG-herhalingsmotief bevat, aangesien hierdie gene as sterk
PFHBI kandidaatgene geag is.
Genotipering en fynkartering deur die gebruik van bekende asook nuwe polimorfiese dinukleotied-
[(CA)n] en nuwe tertranukleotied- [(A3G)n] herhalingsmerkers wat die PFHBI lokus oorbrug, is
uitgevoer. Publieke databanke, soos LLNL (Livermore, USA), en GENEMAP (NCBI) is ondersoek
vir ESTs wat vervolgens verleng is deur gebruik te maak van groeperende programme soos
UNIGENE (NCBI) en STACK (SANBI) en die gevolglike konsensus volgordes is daama met
behulp van BLAST geanaliseer teen die protei'endatabanke. Die bekomde data is vervolgens gebruik om ‘n geintegreerde fisiese en genetiese kaart van die PFHBI lokus te produseer en, soos
die mens genoomprojek gevorder het, is nuwe gene daarop geplaas. Daarna is gene geprioritiseer
vir mutasie analise gebaseer op posisie, funksie en uitdrukkingsprofiele.
Genetiese fynkartering het die PFHBI lokus van 7cM tot 4cM verklein. Die EST benadering het 38
ESTs gei'dentifiseer, waarvan 24 ESTs proteien gelyke gehad het, bv aktiverende transkripsie faktor
5 (ATF5), aktien-verbindingsprotei'en (KPTN) en sink-vingerproteien 473 (ZFP473) (Mei 2003). A1
die karterings data wat eksperimenteel en rekenaar-gewys gegenereer is, is op die PFHBI kaart
geposisioneer. Die P115-RhoGEF is uitgeskakel as ‘n PFHBI kandidaatgeen en alhoewel ’n
volgorde met homologie aan konneksien37 (Kx37) gevind is op albei chromosoom 19 radiasiehibried
klone (RGH12 and ORIM-7), is dit nie gei'dentifiseer in die DNS klone wat die PFHBI
lokus oorbrug nie. Geen bewyse van uitbreiding van CTG herhalingsmotiewe is gevind in PFHBIaangetasde
persone nie. Vyf hoogs-geprioritiseerde kandidaat gene, naamlik, BCL2-geassosieerde
X proteien (BAX), kalium spanningsbeheerde kanaal, subfamilie J, lid 14 (KIR2.4), lin-7 homoloog
B (LIN-7b) en glikogeen sintase 1 (GYS1), is geselekteer vir mutasie-analise. Geen siekteveroorsakende
mutasie is egter gei'dentifiseer in die eksoniese of die naasliggende introniese
gebiede van hierdie gene nie.
Ter opsomming, hierdie studie het die PFHBI lokus verklein en het ‘n omvattende kaart van die
gebied gegenereer. Verskillende kandidaat gene is uitgesluit as die oorsaak van PFHBI, alhoewel
daar nog heelwat goeie kandidaat gene in hierdie geen-ryke lokus is wat geanaliseer behoort te
word. Die identifiseering van die PFHBI-veroorsakende mutasie sal ‘n platform bied vir verdere
studies om die patofisiologie van nie alleen PFHBI nie, maar ook meer algemene
geleidingstoomisse, te verstaan.
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Bioinformatics-based strategies to identify PFHBII-causing and HCM main locus and/or HCM modifying mutationsYako, Yandiswa 12 1900 (has links)
Thesis (MSc)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Progressive familial heart block type II (PFHBII) is an inherited cardiac conduction disorder of
unknown aetiology, which has been described in a South African family. The disorder was
mapped to a 2.9 centimorgan (cM) locus on chromosome 1q32.2-32.3. Clinically, PFHBII
manifests cardiac conduction aberrations, that progress to a disease of the heart muscle, dilated
cardiomyopathy (DCM). DCM is also reported as an end phase in hypertrophic cardiomyopathy
(HCM), another heart muscle disorder. These cardiomyopathies are genetically heterogeneous
with some of the genes reported as causes of both disorders. Therefore, genes identified as causes
of HCM and DCM were considered plausible candidates for PFHBII mutation analysis.
Additionally, this study provided an opportunity to assess potential modifiers of HCM. HCM
exhibits marked phenotypic variability, observed within and between families harbouring the
same causative mutation.
Genes within the PFHBII locus were selected for PCR-SSCP analysis based on homology to
genes previously reported as causing conduction system disorders associated with arrhythmias,
DCM and/or HCM. Results were confirmed by direct sequencing and association between the
detected variants and HCM parameters was assessed using a quantitative transmission
disequilibrium test (QTDT).
Eleven plausible candidate genes were selected within the PFHBII locus and two of the genes,
PFKFB2 and ATF3, that encode for 6-phosphofructo-2,6-bisphosphatase (PFK-2/FBPase-2) and
activating transcription factor 3 (ATF3), respectively, were analysed for PFHBII-causing and
HCM main locus and/or HCM modifying mutations. Mutation analysis of PFKFB2 and ATF3 in
the PFHBII family revealed no PFHBII causal mutation. PFKFB2 and ATF3 were later localised outside the PFHBII locus, and, therefore, were excluded as PFHBII plausible candidates. Further
analysis of the two genes for HCM main locus and/or HCM modifying mutations in the HCM
panel identified several sequence variants. QTDT analysis of these variants showed no significant
association.
Completion of the Human Genome Project (HGP) and annotation of new genes within the
PFHBII locus allowed the identification of more PFHBII plausible candidate genes. Identification
of causal mutations in plausible PFHBII candidate genes will allow molecular diagnosis of
PFHBII pathophysiology. Furthermore, identification of both HCM-modifying and HCM-causing
genes will give insight into the phenotypic variability noted among South African HCM-affected
individuals and into the molecular cause of the disease among individuals with HCM-like clinical
features. / AFRIKAANSE OPSOMMING: Progressiewe familiële hartblok tipe II (PFHBII) is ʼn oorgeërfde hart geleidingsiekte van
onbekende etiologie wat in ʼn Suid-Afrikaanse familie beskryf is. Die siekte is ʼn 2.9 sentimorgan
(cM) lokus op chromosoom 1q32.2-32.3 gekarteer. Klinies presenteer PFHBII met
geleidingsfwykings wat uitloop op gedilateerde kardiomiopatie (DCM). DCM word ook
gerapporteer as ʼn endfase in hipertrofiese kardiomiopatie (HCM), ʼn ander hartspiersiekte. Die
kardiomiopatieë is geneties heterogeen, met ʼn aantal gene wat as oorsaak van altwee
siektetoestande gerapporteer word. Daarom is alle gene wat geïdentifiseer is as oorsake van DCM
en HCM, as moontlike kandidaatgene vir PFHBII mutasieanaliese beskou. Bykomend het hierdie
studie die geleentheid gebied om potensiële modifiseerders van HCM te assesseer. HCM toon
beduidende fenotipiese variasie binne en tussen families wat dieselfde siekteveroorsakende
mutasie het.
Gene binne die PFHBII-lokus is geselekteer vir PCR-SSCP-analiese gebaseer op homologie met
gene wat voorheen gerapporteer is om betrokke te wees by geleidingsiesisteemsiektes,
geassosieerde arritmieë, DCM en/of HCM. Resultate is bevestig deur volgordebepaling.
Assosiasie tusssen ontdekte variante en die siekteparameter is bepaal met ʼn kwantitatiewe
transmissie disekwilibrium toets (QTDT).
Elf moontlike kandidaatgene in die PFHBII-lokus is geselekteer en twee van die gene, PFKFB2
en ATF3, wat kodeer vir 6-fosfofrukto-2,6-bifosfatase (PFK-2/FBPase-2) en
aktiveringstranskripsiefaktor 3 (ATF3) respektiewelik, is vir PFHBII-oorsakende en HCMhooflokus
en/of HCM-modifiseerende mutasies ondersoek. Mutasie-analiese van PFKFB2 en
ATF3 in die PFHBII-familie het nie ʼn siekteveroorsakende mutasie onthul/uitgelig nie. PFKFB2 en ATF3 is later buite die PFHBII-lokus geplaas en dus ook as moontlike PFHBII-kandidate
uitgesluit. Verdere ondersoek van díe twee gene vir HCM-hooflokus en/of HCM-modifiserende
mutasies in die HCM-paneel het ʼn aantal volgorde variante geïdentifiseer. QTDT-analiese van
die variante het geen beduidende assosiasies aangetoon nie.
Voltooiing van die Menslike Genoom Projek (HGP) en annotasie van nuwe gene in die PFHBIIlokus
het tot die identifikasie van verdere moontlike PFHBII-kandidaatgene gelei. Identifikase
van siekte-veroorsaakende mutasies in die moontlike PFHBII-kandidaatgene sal die molekulêre
diagnose van PFHBII toelaat en insig in die patofisiologie van die siekte gee. Verder,
identifikasie van beide HCM-veroorsakende of HCM-modifiserende gene kan insig gee in die
fenotipiese varieerbaarheid wat onder Suid-Afrikaanse HCM-geaffekteerde individue
waargeneem word en ook in die molekulêre oorsake van die siekte in individue met HCMsoortige
kliniese kenmerke.
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A candidate and novel gene search to identify the PFHBII-causative geneFernandez, Pedro (Pedro Wallace) 12 1900 (has links)
Dissertation (PhD)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Heart failure due to cardiomyopathy or cardiac conduction disease is a major cause of
mortality and morbidity in both developed and developing countries. Although defined as
separate clinical entities, inherited forms of cardiomyopathies and cardiac conduction
disorders have been identified that present with overlapping clinical features and/or have
common molecular aetiologies.
The objective of the present study was to identify the molecular cause of progressive familial
heart block type II (PFHBII), an inherited cardiac conduction disorder that segregates in a
South African Caucasian Afrikaner family (Brink and Torrington, 1977). The availability of
family data tracing the segregation of PFHBII meant that linkage analysis could be employed
to identify the chromosomal location of the disease-causative gene. Human Genome Project
(HGP) databases have provided additional resources to facilitate the identification of
positional candidate genes.
Clinical examinations were performed on individuals of the PFHBII-affected family, and,
where available, clinical records of subjects examined in a previous study by Brink and
Torrington (1977) were re-assessed. Retrospective data suggested redefining the classification
of PFHBII. Subsequently, linkage analysis was used to test described dilated cardiomyopathy
(DCM), hypertrophic cardiomyopathy (HCM) and cardiac conduction-causative loci on
chromosomes 1, 2, 3, 6, 7, 9, 11, 14, 15 and 19 for their involvement in the development of
PFHBII. Once a locus was mapped, bioinformatics tools were applied to identify and
prioritise positional candidate genes for mutation screening.
The retrospective and prospective clinical study redefined PFHBII as a cardiac conduction
and DCM-associated disorder and simultaneously allowed more family members to be traced.Fortuitously, candidate loci linkage analysis mapped the PFHBII locus to chromosome 1q32,
to a region that overlapped a previously described DCM-associated disorder (CMD1D), by
the generation of a maximum pairwise lod score of 3.13 at D1S3753 (theta [θ]=0.0) and a
maximum multipoint lod score of 3.7 between D1S3753 and D1S414. However, genetic fine
mapping and haplotype analysis placed the PFHBII-causative locus distal to the CMD1D
locus, within a 3.9 centimorgan (cM) interval on chromosome 1q32.2-q32.3, telomeric of
D1S70 and centromeric of D1S505. Bioinformatics analyses prioritised seven candidate genes
for mutation analysis, namely, a gene encoding a potassium channel (KCNH1), an
extracellular matrix protein (LAMB3), a protein phosphatase (PPP2R5A), an adapter protein
that interacts with a cytoskeletal protein (T3JAM), a putative acyltransferase (KIAA0205) and
two genes encoding proteins possibly involved in energy homeostasis (RAMP and VWS59).
The PFHBII-causative mutation was not identified, although single sequence variations were
identified in four of the seven candidate genes that were screened.
Although the molecular aetiology was not established, the present study defined the
underlying involvement of DCM in the pathogenesis of PFHBII. The new clinical
classification of PFHBII has been published (Fernandez et al., 2004) and should lead to
tracing more affected individuals in South Africa or elsewhere. The identification of a novel
disease-causative locus may point toward the future identification of a new DCM-associated
aetiology, which, in turn, might provide insights towards understanding the associated
molecular pathophysiologies of heart failure. / AFRIKAANSE OPSOMMING: Hartversaking as gevolg van kardiomiopatie of kardiale geleidingsiekte is ‘n hoof-oorsaak
van mortaliteit and morbiditeit in beide ontwikkelde en ontwikkelende lande. Alhoewel
gedefinieer as verskillende kliniese entiteite is oorerflike vorms van kardiomiopatie en
kardiale geleidingsstoornisse geïdentifiseer met oorvleuelende kliniese eienskappe en/of
molukulêre oorsake.
Die doelwit van hierdie studie was om die molukulêre oorsaak van progressiewe familiële
hartblok tipe II (PFHBII), ‘n oorerflike kardiale geleidingsstoornis, wat in ‘n Suid-Afrikaanse
Kaukasiër familie segregeer (Brink en Torrington, 1977), te identifiseer. Die beskikbaarheid
van familie data, beteken dat koppelingsanalise gebruik kan word om die chromosomale
posisie van die siekte-veroorsakende geen te identifiseer. Menslike Genoom Projek (MGP)
databanke het addisionele hulpbronne beskikbaar gestel om die identifikasie van posisionele
kandidaat gene te vergemaklik.
Kliniese ondersoeke is uitgevoer op PFHBII-geaffekteerde familielede, en waar beskikbaar is
kliniese rekords van persone, wat in ‘n vorige studie deur Brink en Torrington (1977)
geassesseer was, herontleed. Retrospektiewe data-analise het die kliniese herdefinisie van
PFHBII voorgestel. Daarna is koppelingsanalise gebruik om dilateerde kardiomiopatie
(DKM), hipertrofiese kardiomiopatie (HKM) en kardiale geleidingssiekte-veroorsakende loki
op chromosoom 1, 2, 3, 6, 7, 9, 11, 14, 15 en 19 te ondersoek vir hul moontlike bydrae tot die
ontwikkeling van PFHBII. Toe die lokus gekarteer was, is bioinformatiese ondersoeke
gebruik om posisionele kandidaat gene te identifiseer en prioritiseer vir mutasie analise.
Die retrospektiewe en prospektiewe kliniese ondersoek het PFHBII herdefinieer as ‘n
geleidingsstoornis en DKM-verbonde siekte, en terselfde tyd het dit gelei tot die opsporingvan nog familielede. Toevallig het kandidaat loki-analise die PFHBII lokus op chromosoom
1q32 gekarteer, na ‘n gebied wat met ‘n voorheen-beskyfde DKM-verbonde stoornis
(CMD1D) oorvleuel, met die opwekking van ‘n makisimum paargewyse lod-getal van 3.13
by D1S3753 (theta [θ] = 0.0) en ‘n maksimum multipunt lod-getal van 3.7 tussen D1S3753 en
D1S414. Genetiese fynkartering en haplotipe-analise het die PFHBII-veroorsakende lokus
afwaards van die CMD1D lokus geplaas, in ‘n 3.9 centimorgan (cM) gebied op chromosoom
1q32.2-q32.3, telomeries van D1S70 en sentromeries van D1S505. Bioinformatiese analise
het daarnatoe gelei dat sewe kandidaat gene vir mutasie analise geprioritiseerd is, naamlik,
gene wat onderskeidelik ‘n kalium kanaal (KCNH1), ‘n ekstrasellulêre matriksproteïen
(LAMB3), ‘n proteïen fosfatase (PPP2R5A), ‘n aansluiter proteïen wat met ‘n sitoskilet
proteïen bind (T3JAM), ‘n asieltansferase (KIAA0205) en twee gene moontlik betrokke in
energie homeostase (RAMP en VWS59) enkodeer. Die PFHBII-veroorsakende geen is nie
geïdentifiseer nie, alhoewel enkele volgorde-wisselings geïdentifiseer is in vier van die sewe
geanaliseerde kandidaat gene.
Alhowel die molekulêre oorsaak van die siekte nie vasgestel is nie, het die huidige studie die
onderliggende betrokkenheid van DKM in die pathogenese van PFHBII gedefinieer. Die
nuwe kliniese klassifikasie van PFHBII is gepubiliseer (Fernandez et al., 2004) en sal lei tot
die identifisering van nog geaffekteerde persone in Suid Afrika of in ander lande. Die
identifikasie van ‘n nuwe siekte-verbonde lokus mag lei tot die toekomstige identifikasie van
‘n nuwe DKM-verbonde genetiese oorsaak wat, opsig self, dalk insig kan gee in die
molekulêre patofisiologie van hartversaking.
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"Contribuição ao estudo da estimulação ventricular e do atrio ventricular universal em portadores da miocardiopatia chagásica: avaliação clínica e hemodinâmica em repuso e exercício" / Clinical and Haemodynamic Evaluation of Ventricular versus Atrioventricular Pacing in Patients with Chagas Cardiomyopathy at Rest and during ExerciseCosta, Roberto 27 July 1990 (has links)
Foram estudados dez pacientes portadores de cardiopatia chagásica, com bloqueio avançado da condução atrioventricular, submetidos a implante de marcapasso atrioventricular universal. Os pacientes foram selecionados a partir do estudo clínico, que identificou os portadores de insuficiência cardíaca congestiva de grau leve (classes funcionais I e II); radiológico, com índice cardiotorácico médio de 0,51 ± 0,05; e ecocardiográfico, com diâmetro diastólico do ventrículo esquerdo médio de 58,2 ± 5,1 mm e fração de encurtamento do ventrículo esquerdo de 0,29 ± 0,08. Pelos critérios ecocardiográficos, cinco pacientes foram considerados morfologicamente normais, três pacientes classificados como portadores de miocardiopatia leve, e dois, de miocardiopatia moderada. O estudo consistiu na avaliação hemodinâmica e metabólica realizada na posição supina, em quatro condições distintas: Modo ventricular em repouso (VVI-R) Modo atrioventricular em repouso (DDD-R) Modo ventricular sob esforço (VVI-E) Modo atrioventricular sob esforço (DDD-E) A programação do marcapasso para o modo ventricular (VVI) constou de freqüência fixa em 70 bpm, enquanto que, para o modo atrioventricular universal (DDD), a freqüência mínima foi de 70 bpm, a máxima, 175 bpm e o intervalo atrioventricular, 150 ms. O esforço foi realizado através de cicloergômetro acoplado à mesa hemodinâmica com carga constante de 50 W/s, durante seis minutos. Foram estudados: a freqüência cardíaca (FC); as pressões médias em átrio direito (PAD), em artéria pulmonar (PAP), em capilar pulmonar (PCP) e na aorta (PA); o índice cardíaco (IC); o índice sistólico (IS); o índice do trabalho sistólico (ITS); a resistência vascular sistêmica (RVS); a resistência arteriolar pulmonar (RAP); a diferença arteriovenosa de oxigênio (Dav02); a extração de oxigênio (E02) e o índice de consumo de oxigênio (IV02). Os resultados obtidos nas condições VVI-R, DDD-R, VVI-E e DDD-E foram, respectivamente: freqüência cardíaca de 72,1 ± 1,4; 79,7 ± 8,8; 71,9 ± 1,2 e 101,2 ± 18,0 bpm; pressão média em átrio direito de 4,8 ± 2,2; 2,6 ± 1,7; 8,3 ± 2,7 e 6,5 ± 3,1 mmHg; pressão média em artéria pulmonar de 17,6 ± 6,2; 14,7 ± 4,1; 26,6 ± 4,5 e 26,7 ± 5,8 mmHg; pressão média em capilar pulmonar de 9,0 ± 3,6; 6,4 ± 2,8; 15,9 ± 4,7 e 14,8 ± 5,7 mmHg; pressão média na aorta de 99,5 ± 7,8; 100,5 ± 7,1 ; 105,4 ± 10,5 e 112,7 ± 10,9 mmHg; índice cardíaco de 2,5 ± 1,0; 2,8 ± 1,2; 3,9 ± 1,4 e 4,7 ± 2,2 l/min.m2; índice sistólico de 34,4 ± 15,1; 35,7 ± 16,1; 54,3 ± 19,9 e 48,0 ± 22,8 ml /m2; índice de trabalho sistólico de 41,9 ± 16,9; 45,2 ± 18,1; 65,8 ± 24,5 e 64,0 ± 30,7 gm/m2; resistência vascular sistêmica de 2347,5 ± 933,4; 2137,6 ± 810,2; 1526,2 ± 699,7 e 1511,6 ± 783,8 dyn.s/cm5; resistência arteriolar pulmonar de 223,7 ± 145,4; 179,2 ± 79,1; 169,9 ± 124,6 e 162,1 ± 76,7 dyn.s/cm5; diferença arteriovenosa de oxigênio de 5,0 ± 1,3; 4,7 ± 2,4; 9,2 ± 3,6 e 8,6 ± 3,1 vol. %; extração de oxigênio de 0,25 ± 0,06; 0,23 ± 0,10; 0,45 ± 0,15 e 0,43 ± 0,14; índice de consumo de oxigênio de 103,2 ± 19,9; 110,0 ± 52,7; 302,5 ± 126,1 e 326,0 ± 115,8 ml/min.m2 . A análise da resposta hemodinâmica demonstrou que a realização do esforço provocou, com o modo ventricular (VVI), aumento do índice cardíaco de 57,7% (p<0,001), propiciado por aumento do índice sistólico de 57,8% (p<0,001) e diminuição da resistência vascular sistêmica de 35,0% (p<0,001); com o modo atrioventricular universal (DDD), aumento do índice cardíaco de 66,8% (p<0,01), devido ao aumento da freqüência cardíaca de 27,0% (p < 0,001), aumento do índice sistólico de 34,2 % (p<0,01) e queda da resistência vascular sistêmica de 29,3 % (p<0,001). A mudança do modo de estimulação ventricular (VVI) para atrioventricular universal (DDD) causou, durante o repouso, aumento do índice cardíaco de 14,1% (NS), resultante da elevação da freqüência cardíaca de 10,5% (p<0.05), do aumento do índice sistólico de 3,8% (NS) e da diminuição da resistência vascular sistêmica de 8,9% (NS); e durante o exercício, aumento do índice cardíaco de 20,6% (p<0.05) propiciado por aumento da freqüência cardíaca de 40,8% (p<0.001), diminuição do índice sistólico de 11,7% (NS) e diminuição da resistência vascular sistêmica de 1,0% (NS). O comportamento individual do índice cardíaco ao exercício, com a mudança do modo de estimulação VVI para DDD, justificou a separação dos resultados em dois grupos distintos de pacientes: no grupo A, ficaram os pacientes que apresentaram queda ou elevação discreta do índice cardíaco (-1,4% em média); e no grupo B, os pacientes que atingiram aumentos expressivos do índice cardíaco (+33,8% em média). A análise estatística demonstrou desempenho hemodinâmico significativamente diferente entre esses dois grupos com relação aos parâmetros índice cardíaco, índice sistólico, índice de trabalho sistólico, resistência vascular sistêmica e resistência arteriolar pulmonar, em todas as condições estudadas. No grupo A, os resultados obtidos nas condições VVI-R, DDD-R, VVI-E e DDD-E, foram, respectivamente: freqüência cardíaca de 73,2 ± 0,7; 82,2 ± 9,7; 72,6 ± 1,0 e 105,2 ± 20,6 bpm; pressão média em átrio direito de 4,6 ± 2,4; 2,4 ± 1,4; 8,0 ± 2,8 e 7,2 ± 2,5 mmHg; pressão média em artéria pulmonar de 18,8 ± 7,6; 16,0 ± 4,3; 28,6 ± 3,3 e 27,8 ± 6,5 mmHg; pressão média em capilar pulmonar de 8,6 ± 3,9; 7,0 ± 2,5; 17,0 ± 6,0 e 16,6 ± 5,6 mmHg; pressão média na aorta de 101,0 ± 10,1; 103,8 ± 6,9; 108,0 ± 11,5 e 114,2 ± 13,0 mmHg; índice cardíaco de 1,8 ± 0,4; 2,0 ± 0,6; 2,8 ± 0,8 e 2,8 ± 0,8 l/min.m2; índice sistólico de 24,8 ± 5,4; 24,8 ± 6,0; 39,2 ± 11,1 e 27,6 ± 7,9 ml/m2; índice de trabalho sistólico de 31,4 ± 8,4; 33,1 ± 9,9; 48,8 ± 16,6 e 37,1 ±12,8 gm/m2; resistência vascular sistêmica de 2953,2 ± 754,0; 2773,6 ± 498,8; 2014,1 ± 632,6 e 2163,3 ± 572,8 dyn.s/cm5; resistência arteriolar pulmonar de 315,5 ± 148,5; 240,4 ± 63,6; 236,7 ± 147,3 e 222,3 ± 59,9 dyn.s/cm5; conteúdo arterial de oxigênio de 19,9 ± 2,6; 19,8 ± 2,7; 20,0 ± 2,4 e 20,0 ± 2,7 vol.%; conteúdo venoso de oxigênio de 14,5 ± 2,3; 15,2 ± 2,1; 9,1 ± 1,5 e 9,3 ± 1,3 vol.%; diferença arteriovenosa de oxigênio de 5,4 ± 1,5; 4,6 ± 1,1; 10,9 ± 2,0 e 10,7 ± 2,3 vol. %; extração de oxigênio de 0,27 ± 0,06; 0,23 ± 0,04; 0,54 ± 0,06 e 0,53 ± 0,06 e índice de consumo de oxigênio de 93,4 ± 16,0; 88,9 ±17,2; 298,6 ± 72,0 e 292,8 ± 90,1 ml/min.m2. No grupo B, os resultados obtidos nas condições VVI-R, DDD-R, VVI-E e DDD-E, foram, respectivamente: freqüência cardíaca de 71,0 ± 1,4; 77,2 ± 6,6; 71,2 ± 0,9 e 97,2 ± 12,7 bpm; pressão média em átrio direito de 5,0 ± 1,8; 2,8 ± 1,9; 8,6 ± 2,9 e 5,8 ± 3,7 mmHg; pressão média em artéria pulmonar de 16,4 ± 3,6; 13,4 ± 3,2; 24,6 ± 5,2 e 25,6 ± 5,0 mmHg; pressão média em capilar pulmonar de 9,4 ± 3,0; 5,8 ± 2,8; 14,8 ± 4,5 e 13,0 ± 5,4 mmHg; pressão média na aorta de 98,0 ± 4,6; 97,2 ± 5,2; 102,8 ± 11,8 e 111,2 ± 11,5 mmHg; índice cardíaco de 3,1 ± 1,1; 3,6 ± 1,3; 4,9 ± 1,2 e 6,6 ± 1,81/min.m2; índice sistólico de 44,0 ± 15,9; 46,7 ± 16,1; 69,4 ± 17,1 e 68,3 ± 17,7 ml/m2; índice de trabalho sistólico de 52,4 ± 17,8; 57,2 ± 17,2; 82,7 ± 19,7 e 90,9 ± 21,6 gm/m2; resistência vascular sistêmica de 1741,7 ± 641,8; 1501,5 ± 617,6; 1038,2 ± 453,4 e 860,0 ± 467,9 dyn.s/cm5; resistência arteriolar pulmonar de 131,9 ± 57,2; 118,0 ± 38,0; 103,0 ± 22,6 e 101,9 ± 43,5 dyn.s/cm5; conteúdo arterial de oxigênio de 20,2 ± 4,3; 20,1 ± 4,3; 20,2 ± 4,2 e 20,1 ± 4,2 vol.%; conteúdo venoso de oxigênio de 15,7 ± 3,6; 15,3 ± 4,0; 13,1 ± 1,6 e 14,3 ± 4,5 vol. %; diferença arteriovenosa de oxigênio de 4,5 ± 0,9; 4,8 ± 3,3; 7,1 ± 4,1 e 5,8 ± 1,3 vol.%; extração de oxigênio de 0,23 ± 0,04 ± 0,23 ± 0,15; 0,33 ± 0,14 e 0,31± 0,11 e índice de consumo de oxigênio de 115,5 ±17,4; 136,3 ± 68,0; 307,5 ±171,1 e 367,5 ± 130,2 ml/min.m2. Durante o seguimento clínico, ocorreram três óbitos dentre os pacientes do grupo A. Não houve óbitos no grupo B. Tendo em vista os resultados obtidos, conclui-se que: 1. Foram identificados dois grupos de pacientes (A e B), que se diferenciaram pelo comportamento do índice cardíaco e da resistência vascular sistêmica, nas condições do presente trabalho. No grupo A, a mudança do modo de estimulação VVI para DDD, durante o exercício, não propiciou aumento do índice cardíaco, a despeito da elevação da freqüência cardíaca, observando-se elevação da resistência vascular sistêmica e diminuição do índice sistólico. No grupo B, a melhora do desempenho hemodinâmico com a mudança do modo de estimulação VVI para DDD, durante exercício, caracterizada pelo aumento do índice cardíaco, deveu-se ao aumento da freqüência cardíaca, manutenção do índice sistólico e diminuição da resistência vascular periférica. 2. Níveis anormalmente elevados de resistência vascular sistêmica, em pacientes chagásicos com bloqueios avançados da condução atrioventricular, têm valor na predição de que a estimulação atrioventricular universal não trará melhora do desempenho hemodinâmico, durante o esforço, quando comparada à estimulação ventricular. / Ten patients with chronic Chagas' cardiomyopathy, high degree atrioventricular block and implanted atrioventricular universal pacemaker, were studied. The population was selected based on Class I or II (NYHA) functional status, cardiothoracic index of 0.51 ± 0.05 (mean ± STD) on X-Ray, and diastolic left ventricular diameter of 58.2 ± 5.1 mm and shortening fraction of 0.29 ± 0.08 on M-mode echocardiogram. According to echocardiografic classification, five patients were normal, three had mild, and two, moderate left ventricular dysfunction. The study consisted of haemodynamic (during standard right and left cardiac catheterization) and metabolic (arterial and venous blood gases) evaluation in supine position of four distinct conditions: ventricular inhibited pacing at rest (VVI-R); universal atrioventricular pacing at rest (DDD-R); ventricular inhibited pacing during exercise (VVI-E); universal atrioventricular pacing during exercise (DDD-E). When in ventricular mode (VVI), the pulse generator was programmed to fixed 70ppm, while, in the atrioventricular universal mode (DDD), the minimum rate was 70 ppm, the upper rate was 175 ppm and the atrioventricular delay was 150 ms. The exercise consisted of standard stress test with 50 Watt/sec during six minutes. This protocol allowed us to analyze the following data: heart rate (HR, bpm); right atrial pressure (RAP, mmHg), mean pulmonary artery pressure (PAP, mmHg); pulmonary wedge pressure (PWP, mmHg); mean aortic pressure (AP, mmHg); cardiac index (CI, I/min.m2 ); stroke index (SI, ml/m2 ); stroke work index (SW, gm/m2); systemic vascular resistance (SVR, dyn.s/cm5); pulmonary arteriolar resistance(PAR, dyn.s/cm5); arteriovenous oxygen difference(DavO2, vol.%); oxygen extraction (EO2) and oxygen uptake (IVO2, ml/min.m2). Obtained results in conditions VVI-R, DDD-R, VVI-E and DDD-E, respectively, were: heart rate 72.1± 1.4, 79.7 ± 8.8, 71.9 ± 1.2 and 101.2 ± 18.0 bpm; right atrial pressure 4.8 ± 2.2, 2.6 ± 1.7, 8.3 ± 2.7 and 6.5 ± 3.1 mmHg; mean pulmonary artery pressure 17.6 ± 6.2, 14.7 ± 4.1, 26.6 ± 4.5 and 26.7 ± 5.8 mmHg; pulmonary wedge pressure 9.0 ± 3.6, 6.4 ± 2.8, 15.9 ± 4.7 and 14.8 ± 5.7 mmHg; mean aortic pressure 99.5 ± 7.8, 100.5 ± 7.1, 105.4 ± 10.5 and 112.7 ± 10.9 mmHg; cardiac index 2.5 ± 1.0, 2.8 ± 1.2, 3.9 ± 1.4 and 4,7 ± 2.2 I/min.m2; stroke index 34.4 ± 15.1, 35.7± 16.1, 54.3 ± 19.9 and 48.0 ± 22.8 ml/m2; stroke work index 41.9 ± 16.9, 45.2 ± 18.1, 65.8 ± 24.5 and 64.0 ± 30.7 gm/m2; systemic vascular resistance 2347.5 ± 933.4, 2137.6 ± 810.2, 1526.2 ± 699.7 and 1511.6 ± 783.8 dyn.s/cm5; pulmonary arteriolar resistance 223.7 ± 145.4, 179.2 ± 79.1, 169.9 ± 124,6 and 162.1 ± 76.7 dyn.s/cm5; arteriovenous oxygen difference 5,0 ± 1.3, 4.7 ± 2.4, 9.2 ± 3.6 and 8.6 ± 3.1vol.%; oxygen extraction 0.25 ± 0.06, 0,23 ± 0.10, 0.45± 0.15 and 0.43± 0.14; oxygen uptake 103.2 ± 19.9, 110.0 ± 52.7, 302.5 ± 126.1 and 326.0 ± 115.8 ml/min.m2. The analysis of the haemodynamic behavior shows that, during VVI pacing, the exercise increased cardiac index of 57.7% (p<0.001 vs VVI at rest), due to an 57.8% (p<0.001) increase of stroke index, and 35.0% (p<0.001) decrease of systemic vascular resistance .During DDD pacing, cardiac index increased 66.8% (p<0.01) due to an 27.0% (p<0.001) increase of heart rate, 34.2 % (p<0.01) increase of stroke index, and 29.3 % (p<0.001) decrease of systemic vascular resistance. The change of pacing mode from VVI to DDD resulted in: 14.1 % (NS) increase of cardiac index due to 10.5% (p<0.05) increase of heart rate, 3.8% (NS) increase of stroke index, and 8.9% (NS) decrease of systemic vascular resistance, at rest; and 20.6% (p<0.05) increase of cardiac index due to 40.8% (p<0.001) increase of heart rate, 11.7% (NS) decrease of stroke index, and 1.0% (NS) decrease of systemic vascular resistance, during exercise. The behavior of cardiac index when the pacing mode was changed from VVI to DDD, during exercise, justified the separation of the patients in two groups: in group A, patients presenting with a fall or mild increase in cardiac index; and, in group B, patients presenting with an expressive increase in cardiac index. The results obtained in group A, for conditions VVI-R, DDD-R, VVI-E and DDD-E were, respectively: heart rate 73.2 ± 0.7, 82.2 ± 9.7, 72.6 ± 1.0 and 105.2 ± 20.6 bpm; right atrial pressure 4.6 ± 2.4, 2.4 ± 1.4, 8.0 ± 2.8 and 7.2 ± 2.5 mmHg; mean pulmonary artery pressure 18.8 ± 7.6, 16.0 ± 4.3, 28.6 ± 3.3 and 27.8 ± 6.5 mmHg; pulmonary wedge pressure 8.6 ± 3.9, 7.0 ± 2.5; 17.0 ± 6.0 and 16.6 ± 5.6 mmHg, mean aortic pressure 101.0 ± 10.1,103.8 ± 6.9, 108.0 ± 11.5 and 114.2 ± 13.0 mmHg; cardiac index 1.8 ± 0.4, 2.0 ± 0.6, 2.8 ± 0.8 and 2.8 ± 0.8 l/min.m2; stroke index 24.8 ± 5.4, 24.8 ± 6.0, 39.2 ± 11.1 and 27.6 ± 7.9 ml/m2; stroke work index 31.4 ± 8.4, 33.1 ± 9.9, 48.8 ± 16.6 and 37.1 ± 12.8 gm/m2; systemic vascular resistance 2953.2 ± 754.0, 2773.6 ± 498.8, 2014.1 ± 632.6 and 2163.3 ± 572.8 dyn.s/cm5; pulmonary arteriolar resistance 315.5 ± 148.5, 240.4 ± 63.6, 236.7 ± 147.3 and 222.3 ± 59.9 dyn.s/cm5; arteriovenous oxygen difference 5.4 ± 1.5, 4.6 ± 1.1, 10.9 ± 2.0 and 10.7 ± 2.3 vol.%; oxygen extraction 0.27 ± 0.06, 0.23 ± 0.04, 0.54 ± 0.06 and 0.53 ± 0.06 and oxygen uptake 93.4 ± 16.0, 88.9 ± 17.2, 298.6 ± 72.0 and 292.8 ± 90.1 ml/min.m2. The results obtained in group B, for conditions VVI-R, DDD-R, VVI-E and DDD-E were, respectively: heart rate 71.0 ± 1.4, 77.2 ± 6.6, 71.2 ± 0.9 and 97.2 ± 12.7 bpm; right atrial pressure 5.0 ± 1.8, 2.8± 1.9, 8 6 ± 2.9 and 5.8 ± 3.7 mmHg; mean pulmonary artery pressure 16.4 ± 3.6, 13.4 ± 3.2, 24.6 ± 5.2 and 25.6 ± 5.0 mmHg; pulmonary wedge pressure 9.4 ± 3.0, 5.8 ± 2.8, 14.8 ± 4.5 and 13.0 ± 5.4 mmHg; mean aortic pressure 98.0 ± 4.6, 97.2 ± 5.2, 102.8 ± 11.8 and 111.2 ± 11.5 mmHg; cardiac index 3.1 ± 1.1, 3.6 ± 1.3, 4.9 ± 1.2 and 6.6 ±.81/min.m2; stroke index 44.0 ± 15.9, 46.7 ± 16.1, 69.4 ± 17.1 and 68.3 ± 17.7 ml/m2; stroke work index 52.4 ± 17.8, 57.2 ± 17.2, 82.7 ± 19.7 and 90.9 ± 21.6 gm/m2; systemic vascular resistance 1741.7 ± 641.8, 1501.5 ± 617.6, 1038.2 ± 453.4 and 860.0 ± 467.9 dyn.s/cm5, pulmonary arteriolar resistance 131.9 ± 57.2, 118.0 ± 38.0, 103.0 ± 22.6 and 101.9 ± 43.5 dyn.s/cm5; arteriovenous oxygen difference 4.5 ± 0.9, 4.8 ± 3.3, 7.1 ± 4.1 and 5.8 ± 1.3 vol.%; oxygen extraction 0.23 ± 0.04, 0.23 ± 0.15, 0.33 ± 0.14 and 0.31 ± 0.11 and oxygen uptake 115.5 ± 17.4, 136.3 ± 68.0, 307.5 ± 171.1and 367.5 ± 130.2 ml/min.m2. During a follow-up period of 64.2 ± 13.4 months, three patients in group A died and no deaths were recorded in group B. We concluded that: 1. The behavior of cardiac index and systemic vascular resistance identified two groups of patients: In group A, the change in pacing mode from VVI to DDD did not improve the haemodynamic response to exercise, because the high systemic vascular resistance prevents stroke index from increase in response to the heart rate. In group B, on the other hand, changing the stimulation mode improved significantly the hemodynamic response to exercise, as far as the low values for systemic vascular resistance allow a better adaptation of stroke index. 2. In Chagas' cardiomyopathy and high degree atrioventricular block, abnormally high values for systemic vascular resistance are useful in selecting patients who will or not benefit from VVI or DDD stimulation.
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