Cardiomyopathies have received attention in the news with well publicized
deaths of prominent young athletes. Cardiomyopathies are a class of heart
disease, classically divided into restrictive, hypertrophic, and dilated.
Most cases are idiopathic, that is, the cause is not known or incompletely
understood. In addition, there are a number of medical diseases including
amyloidosis and alcoholism which may lead to clinical conditions mimicking
these categories of cardiomyopathies. Medical therapy can be used but many
patients may benefit from a heart transplantation.
| PATHOGENESIS |
CHARACTERIZATION |
| HYPERTROPHIC |
|
|
A new mutation of the cardiac troponin T gene causing
familial hypertrophic cardiomyopathy without left ventricular hypertrophy.
Varnava A, Baboonian C, Davison F, de Cruz L, Elliott
PM, Davies MJ, McKenna WJ.
Department of Cardiological Sciences, St George's
Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK.
|
Heart 1999 Nov;82(5):621-4 Abstract quote
AIM: To screen for a mutation of the cardiac troponin T gene in two
families where there had been sudden deaths without an increase in left
ventricular mass but with myocardial disarray suggesting hypertrophic
cardiomyopathy.
METHODS: DNA from affected individuals from both families was used
to screen the cardiac troponin T gene on an exon by exon basis. Mutation
screening was achieved by polymerase chain reaction and direct sequencing.
Where appropriate, a mutation was confirmed by restriction digest.
RESULTS: A novel missense mutation of exon 9 was found in the affected
individuals of one of the families. This mutation at amino acid 94 resulted
in the substitution of arginine for leucine and was not found in 100
normal control samples. A mutation of the cardiac troponin T gene was
excluded in the second family.
CONCLUSIONS: A mutation of the gene for the sarcomeric protein cardiac
troponin T can cause familial hypertrophic cardiomyopathy with marked
myocyte disarray and frequent premature sudden death in the absence
of myocardial hypertrophy at clinical or macroscopic level.
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Clinical features of hypertrophic cardiomyopathy caused
by a Lys183 deletion mutation in the cardiac troponin I gene.
Kokado H, Shimizu M, Yoshio H, Ino H, Okeie K, Emoto
Y, Matsuyama T, Yamaguchi M, Yasuda T, Fujino N, Ito H, Mabuchi H.
Second Department of Internal Medicine, School of
Medicine, Kanazawa University, Kanazawa, Japan.
|
Circulation 2000 Aug 8;102(6):663-9 Abstract quote
BACKGROUND: Mutations that cause hypertrophic cardiomyopathy (HCM)
have been identified in 9 genes that code proteins in the sarcomere.
Previous reports have demonstrated that cardiac troponin I (cTnI) gene
mutations may account for familial HCM; however, the clinical characteristics
and prognosis of patients with HCM caused by cTnI gene mutations are
not known.
METHODS AND RESULTS: We analyzed cTnI gene mutations in 130 unrelated
probands with HCM and their families to clarify the genotype-phenotype
correlations. We identified 25 individuals in 7 families with a Lys183
deletion (Lys183 del) mutation in exon 7 of the cTnI gene. The disease
penetrance in subjects aged >20 years was 88% by echocardiography and
96% by ECG. Sudden death occurred in 7 individuals of 4 families at
any age. Overall, 7 (43.8%) of 16 individuals aged >40 years had left
ventricular systolic dysfunction, and 3 (18.8%) displayed dilated cardiomyopathy-like
features. Of affected individuals, 4 of 5 individuals aged >40 years
followed by echocardiography showed septal thinning and decreased fractional
shortening during >5 years of follow-up.
CONCLUSIONS: The Lys183 del mutation in the cTnI gene in patients with
HCM is associated with variable clinical features and outcomes. HCM
caused by the Lys183 del mutation has a significant disease penetrance.
This mutation is associated with sudden death at any age and dilated
cardiomyopathy-like features in those aged >40 years. However, it remains
unclear whether screening of families with HCM for this mutation will
be useful in patient management and counseling.
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|
Homozygous mutation in cardiac troponin T: implications
for hypertrophic cardiomyopathy.
Ho CY, Lever HM, DeSanctis R, Farver CF, Seidman
JG, Seidman CE.
Cardiovascular Division, Brigham and Women's Hospital,
Harvard Medical School and Howard Hughes Medical Institute, Boston,
MA 02115, USA.
|
Circulation 2000 Oct 17;102(16):1950-5 Abstract quote
BACKGROUND: Mutations in the gene that encode cardiac troponin T (cTnT)
account for approximately 15% of cases of familial hypertrophic cardiomyopathy
(HCM). These mutations are associated with a particularly severe form
of HCM characterized by a high incidence of sudden death and a poor
overall prognosis, despite subclinical or mild left ventricular hypertrophy.
METHODS AND RESULTS: We evaluated a family with HCM and multiple occurrences
of sudden death in children. DNA samples were isolated from peripheral
blood or paraffin-embedded tissue, and all protein-encoding exons of
the cTnT gene were sequenced. A mutation was identified in exon 11 and
is predicted to substitute a phenylalanine-for-serine mutation at residue
179 (Ser(179)Phe) in cTnT. Both parents and 3 of 4 surviving and clinically
unaffected children were heterozygous for this mutation; another clinically
unaffected child did not carry the mutation. Genetic analysis of DNA
from a child who died suddenly at age 17 years demonstrated he was homozygous
for this mutation. A review of his echocardiogram revealed profound
left and right ventricular hypertrophy.
CONCLUSIONS: An homozygous Ser(179)Phe mutation in cTnT causes a severe
form of HCM characterized by striking morphological abnormalities and
juvenile lethality. In contrast, the natural history of the heterozygous
mutation is benign. These studies emphasize the relevance of genetic
diagnosis in hypertrophic cardiomyopathy and provide a new perspective
on the clinical consequences of troponin T mutations.
|
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Phenotypic variation of familial hypertrophic cardiomyopathy
caused by the Phe(110)-->Ile mutation in cardiac troponin T.
Lin T, Ichihara S, Yamada Y, Nagasaka T, Ishihara
H, Nakashima N, Yokota M.
Department of Clinical Laboratory Medicine, Nagoya
University School of Medicine, Nagoya, Japan.
|
Cardiology 2000;93(3):155-62 Abstract quote
Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant
of familial hypertrophic cardiomyopathy (HCM).
A Japanese family of 14 individuals, including 6 with HCM, was subjected
to genetic and clinical assessment. Five exons of the cTnT gene were
sequenced in all family members. A heterozygous or homozygous T(340)-->A
(Phe(110)-->Ile) mutation in exon 9 of the cTnT gene was detected in
11 subjects. Morphological and functional evaluation of the left and
right ventricles by echocardiography revealed that 4 of 9 individuals
heterozygous for the mutant allele exhibited HCM with moderate cardiac
hypertrophy. Cardiac hypertrophy and other clinical features in the
2 subjects homozygous for the mutation were more severe than were those
in heterozygous individuals with HCM.
Thus, the clinical features of HCM due to the Phe(110)-->Ile mutation
in the cTnT gene appear to be modified by a gene dosage effect.
|
| RESTRICTIVE |
|
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The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive
cardiomyopathy.
Liao P, Georgakopoulos D, Kovacs A, Zheng M, Lerner D, Pu H, Saffitz
J, Chien K, Xiao RP, Kass DA, Wang Y.
Department of Physiology, University of Maryland School of Medicine,
Baltimore, MD 21201, USA.
|
Proc Natl Acad Sci U S A 2001 Oct 9;98(21):12283-8 Abstract quote
Stress-induced mitogen-activated protein kinase (MAP) p38 is activated
in various forms of heart failure, yet its effects on the intact heart
remain to be established.
Targeted activation of p38 MAP kinase in ventricular myocytes was achieved
in vivo by using a gene-switch transgenic strategy with activated mutants
of upstream kinases MKK3bE and MKK6bE. Transgene expression resulted
in significant induction of p38 kinase activity and premature death
at 7-9 weeks. Both groups of transgenic hearts exhibited marked interstitial
fibrosis and expression of fetal marker genes characteristic of cardiac
failure, but no significant hypertrophy at the organ level. Echocardiographic
and pressure-volume analyses revealed a similar extent of systolic contractile
depression and restrictive diastolic abnormalities related to markedly
increased passive chamber stiffness. However, MKK3bE-expressing hearts
had increased end-systolic chamber volumes and a thinned ventricular
wall, associated with heterogeneous myocyte atrophy, whereas MKK6bE
hearts had reduced end-diastolic ventricular cavity size, a modest increase
in myocyte size, and no significant myocyte atrophy.
These data provide in vivo evidence for a negative inotropic and restrictive
diastolic effect from p38 MAP kinase activation in ventricular myocytes
and reveal specific roles of p38 pathway in the development of ventricular
end-systolic remodeling.
|
| DILATED |
|
|
Sudden death in dilated cardiomyopathy.
Wu AH, Das SK.
Department of Internal Medicine, University of Michigan
Medical Center, Ann Arbor 48109, USA.
|
Clin Cardiol 1999 Apr;22(4):267-72 Abstract quote
The purpose of this review is to examine the potential contribution
of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy
(DCM) and to discuss current treatment options.
We performed a search of the MEDLINE database from 1985 to the present
and the reference citations of selected articles pertaining to the prognostic
significance, management, and pathophysiology of arrhythmias in DCM.
A large proportion of patients with DCM die suddenly, most secondary
to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia.
The presence and severity of ventricular ectopy may predict risk for
sudden death, but the role of electrophysiologic study and signal-averaged
electrocardiography in further risk stratifying patients remains uncertain.
Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone
axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting
enzyme inhibitors improve overall mortality in congestive heart failure,
and the use of direct angiotensin-receptor antagonists is currently
being studied. In addition, beta-receptor antagonists appear to improve
morbidity and may prove to improve mortality in heart failure as well.
Other interventions still under investigation include amiodarone and
the implantable cardioverter-defibrillator.
The underlying pathophysiology of sudden death in DCM involves primarily
ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors
remain a mainstay of improving overall mortality, while further study
on the roles for newer drugs and devices is ongoing.
|
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Human eHAND, but not dHAND, is down-regulated in cardiomyopathies.
Natarajan A, Yamagishi H, Ahmad F, Li D, Roberts R,
Matsuoka R, Hill S, Srivastava D.
Division of Intensive Care, Department of Pediatrics,
University of Texas Southwestern Medical Center, University of Texas
Southwestern Medical Center, One Baylor Plaza, Dallas, Texas 75390-9148,
USA.
|
J Mol Cell Cardiol 2001 Sep;33(9):1607-14 Abstract quote
The progression of cardiomyopathy to congestive heart failure is often
associated with the expression of fetal cardiac-specific genes. In mice,
the basic helix-loop-helix transcription factors, dHAND and eHAND, are
expressed in a cardiac chamber-specific fashion and are essential for
fetal cardiac development, but are down-regulated in the adult. Their
expression in specific chambers of healthy and diseased human hearts
has not been studied previously.
Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33,
respectively, by fluorescent in situ hybridization. RNA from the four
chambers of healthy human adult hearts, and from hearts of patients
with several forms of cardiomyopathy, was obtained and assayed for dHAND
and eHAND expression. Unlike in mice, dHAND expression was observed
in all four chambers of the healthy human adult heart, but was diminished
in the right atrium. In contrast, eHAND was expressed in the right and
left ventricles, but was downregulated in both atrial chambers. We examined
tissue from 15 human cardiomyopathic hearts obtained during cardiac
transplantation or by endomyocardial biopsy for alterations in HAND
gene expression. dHAND expression was unchanged in all forms of cardiomyopathy
tested. However, cardiac expression of eHAND was severely down-regulated
in six of six patients with ischemic cardiomyopathy and six of six patients
with dilated cardiomyopathy.
This study demonstrates that human dHAND and eHAND have unique spatial
patterns of expression within human cardiac chambers. Downregulation
of eHAND in ischemic and dilated cardiomyopathy suggests a correlation
between eHAND dysregulation and the evolution of a subset of cardiomyopathies.
|
|
Human coxsackie-adenovirus receptor is colocalized
with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte
sarcolemma and upregulated in dilated cardiomyopathy: implications for
cardiotropic viral infections.
Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers
D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M,
Hetzer R, Lamers J, Schultheiss HP, Poller W.
Department of Cardiology and Pneumology, University
Hospital Benjamin Franklin, Freie Universitat, Berlin, Germany.
|
Circulation 2001 Jul 17;104(3):275-80 Abstract quote
BACKGROUND: The coxsackievirus and adenovirus receptor (CAR) was identified
as a common cellular receptor for both viruses, but its biological and
pathogenic relevance is uncertain. Knowledge of CAR localization in
the human cardiovascular system is limited but important with respect
to CAR-dependent viral infections and gene transfer using CAR-dependent
viral vectors.
METHODS AND RESULTS: Explanted failing hearts from 13 patients (8 with
dilated cardiomyopathy [DCM] and 5 with other heart diseases [non-DCM])
and normal donor hearts (n=7) were investigated for the expression levels
and subcellular localization of CAR and the adenovirus coreceptors alpha(v)beta(3)
and alpha(v)beta(5) integrins. CAR immunoreactivity was very low in
normal and non-DCM hearts, whereas strong CAR signals occurred at the
intercalated discs and sarcolemma in 5 of the 8 DCM hearts (62.5%);
these strong signals colocalized with both integrins. In all hearts,
CAR was detectable in subendothelial layers of the vessel wall, but
not on the luminal endothelial surface, and on interstitial cells. Human
CAR (hCAR) expressed in rat cardiomyocytes was targeted to cell-cell
contacts, which resembled CAR localization in DCM hearts and resulted
in 15-fold increased adenovirus uptake.
CONCLUSIONS: Low hCAR abundance may render normal human myocardium
resistant to CAR-dependent viruses, whereas re-expression of hCAR, such
as that observed in DCM, may be a key determinant of cardiac susceptibility
to viral infections. Asymmetric expression of hCAR in the vessel wall
may be an important determinant of adenovirus tropism in humans. hCAR
subcellular localization in human myocardium and hCAR targeting to cell-cell
contacts in cardiomyocyte cultures suggest that hCAR may play a role
in cell-cell contact formation.
|
| HISTOLOGICAL TYPES |
CHARACTERIZATION |
| GENERAL |
|
| HYPERTROPHIC |
|
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Hypertrophic cardiomyopathy: histopathological features
of sudden death in cardiac troponin T disease.
Varnava AM, Elliott PM, Baboonian C, Davison F, Davies
MJ, McKenna WJ.
Department of Cardiological Sciences, St George's
Hospital Medical School, Cranmer Terrace, London, UK.
|
Circulation 2001 Sep 18;104(12):1380-4 Abstract quote
BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at
increased risk of premature death; this is particularly apparent for
patients with mutations of the troponin T gene. Myocyte disarray and
interstitial fibrosis, pathological features of HCM, may be determinants
in these deaths. The relation between genotype, pathological phenotype,
and mode of death has not been explored.
METHODS AND RESULTS: Seventy-five hearts with HCM were examined. DNA
was available in 50 for screening of the troponin T gene. The macroscopic
findings, percentage of disarray, percentage of fibrosis, and percentage
of small-vessel disease were correlated with the genotype. A troponin
T mutation was identified in 9 of the 50 patients, 8 of whom died suddenly.
Patients with a troponin T mutation were younger (mean age, 21.0 years
[range, 6 to 37] versus 39.1 years [range, 14 to 72]; P<0.0001), had
more sudden death (P=0.02), and had lower heart weights, less fibrosis,
and greater disarray than other HCM patients (mean heart weight, 380.3+/-105.4
versus 585.0+/-245.7 g, P=0.002; mean fibrosis, 0.7+/-0.4% versus 2.6+/-2.8%,
P=0.001; mean disarray, 46.2+/-7.2% versus 24.1+/-15.9%, P<0.0001; and
mean small-vessel disease, 11.7+/-14.6 versus 14.1+/-8.7, P=0.6, respectively).
Similarly, patients with troponin T mutations who died suddenly had
lower heart weights and greater disarray than patients who died suddenly
with unknown genotype (ie, troponin T mutation excluded) (mean heart
weight, 429.8+/-75.4 versus 559.6+/-204.43 g, P=0.04, and mean disarray,
40.1+/-9.4% versus 20.2+/-12.6%, P=0.002, respectively).
CONCLUSIONS: Patients with troponin T mutations had severe disarray,
with only mild hypertrophy and fibrosis. These patients died suddenly
and at an especially early age. We propose that extensive myocyte disarray
in the absence of marked hypertrophy is the pathological substrate for
sudden death in these patients.
|
| RESTRICTIVE |
|
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Spectrum of restrictive cardiomyopathy: report of
the national survey in Japan.
Hirota Y, Shimizu G, Kita Y, Nakayama Y, Suwa M, Kawamura
K, Nagata S, Sawayama T, Izumi T, Nakano T, et al.
Department of Internal Medicine, Osaka Medical College,
Japan.
|
Am Heart J 1990 Jul;120(1):188-94 Abstract quote
This report describes clinical profiles and echocardiographic, hemodynamic,
and histologic findings in 26 cases of idiopathic RCM based on the diagnostic
criteria of (1) heart failure resulting from a stiff left ventricle,
(2) normal LV size and systolic function, (3) absence of LV hypertrophy,
and (4) cause or association unknown.
There were 14 male and 12 female patients ranging in age from 5 to
63 years. Ten patients died during the mean follow-up period of 145
months, and five died of heart failure after 10 years. Three had a family
history of HCM. Thromboembolism was observed in eight. Echocardiograms
showed normal LV wall thickness and contraction. Hemodynamic characteristics
included elevated biventricular filling pressures and a pulmonary wedge
pressure that was usually higher than the right atrial pressure. Equalization
of biventricular filling pressures was seen, however, in almost all
patients with severe tricuspid regurgitation (seven of eight). The square
root sign was seen in 50% in RV diastolic pressure tracings and 28%
in LV tracings. This sign was observed in patients with elevated filling
pressures. Interstitial fibrosis (22 of 23), endocardial thickening
(13 of 23), and myofibrillar hypertrophy (10 of 23) were common histologic
findings. Severe myocardial fiber disarray consistent with HCM was seen
in four patients.
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Idiopathic restrictive cardiomyopathy in childhood.
A diastolic disorder characterized by delayed relaxation.
Gewillig M, Mertens L, Moerman P, Dumoulin M.
Department of Pediatric Cardiology, Gasthuisberg University
Hospital, Leuven, Belgium.
|
Eur Heart J 1996 Sep;17(9):1413-20 Abstract quote
Six children with idiopathic restrictive cardiomyopathy were evaluated.
Electrocardiographic evaluation disclosed left atrial dilatation and
repolarization abnormalities. Echocardiographic examination showed gross
left atrial enlargement (182 +/- 29% of predicted values, P < 0.001)
in the presence of normal left ventricular cavity dimensions (99 +/-
6%, P: ns). Left ventricular wall thickness varied from normal to mild
concentric hypertrophy (septum: 116 +/- 16%, P < 0.05). Global left
ventricular systolic function was normal or slightly subnormal; however,
the relaxation was significantly delayed throughout diastole. E/A ratio
was 4.1 +/- 1.4 and deceleration time 94 +/- 7 ms. Marked ventricular
filling occurred in mid-diastole as could be deduced from a prominent
mid-diastolic mitral L wave on the Doppler flow tracing. Early filling
contributed 56 +/- 6%, mid-diastolic filling 28 +/- 4% and atrial contraction
16 +/- 3% to total ventricular filling as estimated by determining E-area,
L-area and A-area, respectively. The left ventricular pressure curve
showed a steady decline during mid-diastolic filling. This implies that
the driving force for mid-diastolic filling is not the increased left
atrial pressure but suction by the ventricle.
The restrictive haemodynamics are therefore not caused by increased
intrinsic stiffness of the ventricular wall, but most likely result
from serious dysfunction and delay of the active relaxation of the ventricle.
Progression of the disease was observed in three out of six patients,
resulting in death or extreme low cardiac output. The three other patients
remained clinically stable during the follow-up period of 6-10 years.
|
|
Clinical profile and outcome of idiopathic restrictive
cardiomyopathy.
Ammash NM, Seward JB, Bailey KR, Edwards WD, Tajik
AJ.
Division of Cardiovascular Diseases and Internal Medicine,
Mayo Clinic and Mayo Foundation, Rochester, Minn. 55905, USA.
|
Circulation 2000 May 30;101(21):2490-6 Abstract quote
BACKGROUND: Idiopathic restrictive cardiomyopathy is a poorly recognized
entity of unknown cause characterized by nondilated, nonhypertrophied
ventricles with diastolic dysfunction resulting in dilated atria and
variable systolic function.
METHODS AND RESULTS: Between 1979 and 1996, 94 patients (61% women)
10 to 90 years old (mean, 64 years) met strict morphological echocardiographic
criteria for idiopathic restrictive cardiomyopathy, mainly dilated atria
with nonhypertrophied, nondilated ventricles. None had known infiltrative
disease, hypertension of >5 years' duration, or cardiac or systemic
conditions associated with restrictive filling. Nineteen percent were
in NYHA class I, 53% in class II, and 28% in class III or IV. Atrial
fibrillation was noted in 74% of patients and systolic dysfunction in
16%. Follow-up (mean, 68 months) was complete for 93 patients (99%).
At follow-up, 47 patients (50%) had died, 32 (68%) of cardiovascular
causes. Four had heart transplantation. The death rate compared with
actuarial statistics was significantly higher than expected (P<0.0001).
Kaplan-Meier 5-year survival was 64%, compared with expected survival
of 85%. Multivariate analysis using proportional hazards showed that
the risk of death approximately doubles with male sex (hazard ratio
[HR] = 2.1), left atrial dimension >60 mm (HR = 2.3), age >70 years
(HR = 2.0), and each increment of NYHA class (HR = 2.0).
CONCLUSIONS: Idiopathic restrictive cardiomyopathy or nondilated, nonhypertrophic
ventricles with marked biatrial dilatation, as defined morphologically
by echocardiography, affects predominantly elderly patients but can
occur in any age group. Patients present with systemic and pulmonary
venous congestion and atrial fibrillation and have a poor prognosis,
particularly men >70 years old with higher NYHA class and left atrial
dimension >60 mm.
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| DILATED |
|
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Apoptosis in myocarditis and dilated cardiomyopathy:
Does enterovirus genome persistence protect from apoptosis? - An endomyocardial
biopsy study.
Alter P, Jobmann M, Meyer E, Pankuweit S, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University
Marburg/Lahn, Baldingerstrasse, D-35033, Marburg, Germany
|
Cardiovasc Pathol 2001 Sep-Oct;10(5):229-34 Abstract quote
The purpose of this study was to examine the role of apoptosis in myocarditis
and dilated cardiomyopathy. Apoptosis is an active energy-consuming
mechanism of cell death in several cardiac diseases in different quality
and quantity.
Methods: Endomyocardial biopsies from 81 patients with active (1)
and chronic myocarditis (10), dilated cardiomyopathy with inflammation
(DCMi; 10) and without inflammation (DCM; 20), with borderline myocarditis
and positive PCR for cytomegalovirus-DNA (6), adenovirus-DNA, or enterovirus-RNA
(7), and controls (17) were analysed. Apoptosis was detected by using
the TUNEL method.
The highest rate of apoptotic cardiocytes was found in active and chronic
myocarditis. One patient with severe active myocarditis demonstrated
6.15% of apoptotic cardiocytes. Mean percentage of apoptotic cardiocytes
in chronic myocarditis was significantly increased (0.61+/-1.25%) when
compared to controls (0.01+/-0.04%, P<.05). Particularly, patients with
cytomegalovirus-DNA persistence in borderline myocarditis had an elevated
rate of apoptosis (0.34+/-0.68%, P<.05). Increased rates of apoptosis
were found in borderline myocarditis with adenovirus-DNA persistence
(0.20+/-0.57%) and in DCM (0.06+/-0.15%). Only a nonsignificant increase
of apoptotic cardiocytes was found in DCMi (0.03+/-0.08%). No apoptosis
was found in patients with enteroviral genome persistence in borderline
myocarditis.
Conclusions: Apoptosis of cardiac cells is increased in myocarditis
and dilated cardiomyopathy, being highest in severe active myocarditis.
Apoptosis thus contributes to cell death in active myocarditis and may
play a role not to be neglected in dilated cardiomyopathy. Enteroviruses
seem to have anti-apoptotic effects, because no apoptosis at all was
found in the myocardium.
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| VARIANTS |
|
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Arrhythmogenic right ventricular cardiomyopathy: Clinicopathologic
correlation based on a revised definition of pathologic patterns
Giulia D'Amati, PhD
Ornella Leone, MD
Cira Rosaria Tiziana di Gioia, PhD, etal.
|
Hum Pathol 2001;32:1078-1086. Abstract quote
Different morphologic features of arrhythmogenic right ventricular
cardiomyopathy (ARVC) have been described. However, it is still unclear
whether they correspond to distinct forms of the same disease.
A pathologic study was performed on a series of ARVC (15 from heart
transplant and 12 from autopsy) from 2 Italian referral university hospitals.
Based on both myocellular features and the nature of myocardial replacement,
hearts were divided into 2 groups: infiltrative, with a lacelike pattern
of transmural fatty infiltration and strands of normal residual cardiomyocytes
(n = 11); and cardiomyopathic, with massive myocardial replacement by
fibro fatty tissue and cardiomyopathic changes (such as hypertrophy
and myofibril loss) of residual cardiomyocytes (n = 16). Hearts from
the infiltrative group were mostly obtained at autopsy of patients who
died suddenly. Fatty substitution was limited almost exclusively to
the right ventricle. Mitral valve dysplasia (prolapse or cleft) was
frequently present. Hearts from the cardiomyopathic group came mainly
from heart transplants for congestive heart failure. Fibro fatty replacement
was more extensive, usually biventricular. Active myocarditis and features
suggestive of myocardial transdifferentiation were also observed.
Despite these differences in clinical outcome and morphologic features,
patients from the 2 groups showed similar mean age, sex distribution,
occurrence of threatening ventricular arrhythmias, and prevalence of
family history of sudden death, arrhythmias, or cardiomyopathy.
Infiltrative and cardiomyopathic patterns represent different clinical
and pathologic subsets of ARVC. Myocellular features are an important
clue in the distinction between the two entities. The differentiation
between the 2 patterns is feasible on endomyocardial biopsy and could
give important prognostic information.
|
| PROGNOSIS AND TREATMENT |
CHARACTERIZATION |
| PROGNOSTIC FACTORS |
|
| HYPERTROPHIC |
|
|
Hypertrophic cardiomyopathy: the interrelation of
disarray, fibrosis, and small vessel disease.
Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies
MJ.
Department of Cardiovascular Pathology, St George's
Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
|
Heart 2000 Nov;84(5):476-82 Abstract quote
OBJECTIVE: To make a quantitative assessment of the relation between
disarray, fibrosis, and small vessel disease in hypertrophic cardiomyopathy.
DESIGN: Detailed macroscopic and histological examination at 19 segments
of the left and right ventricle and the left atrial free wall.
PATIENTS: 72 patients with hypertrophic cardiomyopathy who had suffered
sudden death or progression to end stage cardiac failure (resulting
in death or heart transplantation).
MAIN OUTCOME MEASURES: The presence of scarring, atrial dilatation,
and a mitral valve impact lesion were noted, and heart weight, wall
thickness, per cent disarray, per cent fibrosis, and per cent small
vessel disease quantitated for each heart.
RESULTS: Within an individual heart the magnitude of hypertrophy correlated
with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002).
Overall, however, total heart weight related weakly but significantly
to fibrosis (r = 0.4, p = 0.0001) and small vessel disease (r = 0.3,
p = 0.03), but not to disarray. Disarray was greater in hearts with
mild left ventricular hypertrophy (maximum wall thickness < 20 mm) and
preserved systolic function (60.9 (26)% v 43 (20.4)% respectively, p
= 0.02) and hearts without a mitral valve impact lesion (26.3% v 18.9%,
p = 0.04), but was uninfluenced by sex. Fibrosis was influenced by sex
(7% in male patients and 4% in female, p = 0.04), but not by the presence
of an impact lesion. No relation was found between disarray, fibrosis,
and small vessel disease.
CONCLUSIONS: Myocyte disarray is probably a direct response to functional
or structural abnormalities of the mutated sarcomeric protein, while
fibrosis and small vessel disease are secondary phenomena unrelated
to disarray, but modified by factors such as left ventricular mass,
sex, and perhaps local autocrine factors.
|
|
Relation between myocyte disarray and outcome in hypertrophic
cardiomyopathy.
Varnava AM, Elliott PM, Mahon N, Davies MJ, McKenna
WJ.
Department of Cardiovascular Pathology and Cardiological
Sciences, St George's Hospital Medical School, London, United Kingdom.
|
Am J Cardiol 2001 Aug 1;88(3):275-9 Abstract quote
Hypertrophic cardiomyopathy (HC) is associated with an increased risk
of sudden cardiac death or death from heart failure. Little is known
of the pathologic substrate for risk of premature death in this disease.
We therefore set out to correlate the pathologic findings with the
mode of death and risk profile in 75 patients with HC. Hearts with HC
were obtained after death or transplantation.
The clinical details were correlated with the macroscopic findings
and the percent fibrosis, disarray, and small-vessel disease across
19 sections of each heart. Thirty-nine patients died suddenly, 28 had
end-stage heart failure, and 8 died of other causes. Myocyte disarray
correlated positively with evidence of ischemia (r = 0.5, p <0.0001),
and was greater in patients who died before age 21 years (mean disarray
33% vs 18%, p <0.0001) and in those with an abnormal vascular response
to exercise (mean disarray and 30% vs 19%, p = 0.04). Myocardial fibrosis
was greater in patients who died in heart failure (mean percent fibrosis
was 2.8% versus 0.9%, p = 0.003), and in patients with nonsustained
ventricular tachycardia or a high risk fractionation study (4.9% vs
2.7%, p = 0.04, and 6.84% vs 2.8%, p = 0.03, respectively).
In conclusion, young patients who die with HC have greater disarray
than their older counterparts. In contrast, myocardial fibrosis is the
substrate for premature deaths from heart failure and is associated
with an increased risk of a primary ventricular arrhythmia.
|
| RESTRICTIVE |
|
|
Clinical profile and outcome of restrictive cardiomyopathy
in children.
Lewis AB.
Division of Cardiology, Childrens Hospital of Los
Angeles, CA 90054-0700.
|
Am Heart J 1992 Jun;123(6):1589-93 Abstract quote
The clinical profile and outcome of idiopathic restrictive cardiomyopathy
in a group of eight children are reviewed.
There were six girls and two boys. Age at presentation was 4.0 +/-
2.6 years (range 1.3 to 9.5 years). All patients had evidence of congestive
heart failure with systemic venous congestion. Right or left atrial
enlargement was the most consistent ECG finding and was present in all
patients. Left ventricular shortening fraction was normal in five patients,
increased in two, and mildly reduced in one. The most striking echocardiographic
feature was severe biatrial dilatation in the presence of normal or
near-normal ventricular cavity dimensions. Marked elevation of left
ventricular end-diastolic pressure was noted in all seven patients undergoing
cardiac catheterization (34 +/- 7 torr; range 24 to 40 torr). Right
ventricular end-diastolic pressure was elevated but significantly different
from left ventricular pressure (18 +/- 7 torr; p less than 0.01). A
characteristic early diastolic dip with a rapid rise to an elevated
plateau (square root sign) was present in five of seven patients. Median
survival was 1.4 years. Six patients died 0.2 to 7.0 years after they
were initially seen. The actuarial survival rate 1.5 years after presentation
was 44%, decreasing to 29% at 4 years.
Restrictive cardiomyopathy has a worse prognosis in children than in
adults. In part this may reflect the more advanced symptoms of congestive
failure at initial presentation. Pediatric patients should be considered
for early cardiac transplantation.
|
|
Clinical spectrum of restrictive cardiomyopathy in
children.
Chen SC, Balfour IC, Jureidini S.
Saint Louis University School of Medicine, Department
of Pediatrics and Cardinal Glennon Children's Hospital, 1465 South Grand
Blvd., St. Louis, MO 63104-1095, USA.
|
J Heart Lung Transplant 2001 Jan;20(1):90-2 Abstract quote
We reviewed the clinical spectrum and possible prognostic factors in
14 children with restrictive cardiomyopathy. The patients were not homogeneous
in clinical presentation or morphology. The mortality rate was high:
21.4% at 1 year and 50% at 2 years after presentation.
Younger patients with respiratory symptoms, thromboembolism, increased
cardiothoracic ratio on chest radiogram or patients with endocardial
fibroelastosis appear to have a worse prognosis and orthotopic cardiac
transplantation may be indicated.
|
| DILATED |
|
|
Infantile dilated cardiomyopathy. Relation of outcome
to left ventricular mechanics, hemodynamics, and histology at the time
of presentation.
Matitiau A, Perez-Atayde A, Sanders SP, Sluysmans
T, Parness IA, Spevak PJ, Colan SD.
Department of Cardiology, Children's Hospital, Harvard
Medical School, Boston, Mass. 02115.
|
Circulation 1994 Sep;90(3):1310-8 Abstract quote
BACKGROUND: For patients with acute dilated cardiomyopathy, definition
of prognosis and of clinical features predictive of outcome is particularly
important due to the availability of cardiac transplantation and other
innovative treatment strategies.
METHODS AND RESULTS: We reviewed our experience with 24 children under
2 years of age with dilated congestive cardiomyopathy to determine outcome
and potential predictive variables. Clinical, serological, ECG, echocardiographic,
hemodynamic, and histological findings were analyzed. Idiopathic cardiomyopathy
or myocarditis constituted 29% of the patients presenting with congestive
heart failure without structural heart disease. Among these patients,
45% recovered completely, 25% survived with persistent left ventricular
dysfunction, and 30% died. All except one of the deaths occurred during
the first 2 months after presentation. Poorer outcome and higher mortality
were associated with a more severely depressed left ventricular ejection
fraction and/or a more spherical left ventricular shape at presentation.
Histological evidence of myocardial inflammation was a favorable prognostic
indicator, whereas histological evidence of endocardial fibroelastosis
was associated with a poor outcome. During the recovery phase, diastolic
volume fell rapidly. Ventricular mass was elevated from the earliest
observations and fell more slowly, with persistent elevation of the
mass-to-volume ratio up to 2 years. Function and contractility improved
over the first several months in most patients who recovered, although
in occasional patients continued improvement was seen for as long as
2 years after presentation.
CONCLUSIONS: Histological and echocardiographic features can be used
to identify patients at particularly high risk for death. To have any
impact on outcome, decisions about cardiac transplantation must be reached
rapidly, since almost all deaths occurred within the first 2 months
after presentation. Recovery of function is often rapid, but continued
improvement may be seen for as long as 2 years.
|
|
Prognostic value of posterior wall thickness in childhood
dilated cardiomyopathy and myocarditis.
Carvalho JS, Silva CM, Shinebourne EA, Redington AN.
Department of Paediatric Cardiology, Royal Brompton
National Heart and Lung Hospital, London, U.K.
|
Eur Heart J 1996 Aug;17(8):1233-8 Abstract quote
M-mode indices of left ventricular dimension and posterior wall thickness
were derived from echocardiograms of children presenting with dilated
cardiomyopathy/myocarditis and were related to outcome.
Echocardiograms from 16 of 18 children were manually digitized to
obtain changes of left ventricular dimension and posterior wall thickness
throughout the cardiac cycle. Indices of ventricular function and the
ratio of end-diastolic posterior wall thickness to cavity dimensions
were obtained. Patients were divided into group I (alive, n = 7), and
group II (died, n = 6 or heart transplantation, n = 3) at median follow-up
of 25 months. No significant difference was seen for the shortening
fraction, the percentage of posterior wall thickening or the normalized
peak rate of left ventricular filling. The normalized peak rate of posterior
wall thinning was greater in group II. The posterior wall thickness
to cavity dimension ratio was higher in group I (median = 0.19) than
group II (median = 0.13) (P < 0.005). Five of six survivors, whose ventricular
function improved, had ratios > 0.17. All but one with a ratio < or
= 0.16 remained with a dilated heart, died or required transplantation
(P = < 0.01).
A relatively thicker posterior wall (ratio > 0.17) was associated with
better prognosis and recovery. This index should be taken into account
in decision-making regarding timing for cardiac transplantation.
|
|
Idiopathic dilated cardiomyopathy in children: prognostic
indicators and outcome.
Arola A, Tuominen J, Ruuskanen O, Jokinen E.
Department of Pediatrics, University of Turku, Turku,
Finland.
|
Pediatrics 1998 Mar;101(3 Pt 1):369-76 Abstract quote
OBJECTIVE: To determine the outcome of Finnish children and adolescents
with idiopathic dilated cardiomyopathy (IDCM) and factors that might
be useful as prognostic indicators.
METHODOLOGY: The clinical profile and course of 62 Finnish children
and adolescents (median age, 13 months; range, 1 day to 20 years) with
IDCM in 1980 to 1991 were evaluated to detect factors that might predict
outcome. Factors studied included age, gender, family history, previous
viral illness, and symptoms and signs at presentation. Furthermore,
data on serial electrocardiographic, echocardiographic, and chest x-ray
examinations, histologic findings, and treatments were analyzed.
RESULTS: During a mean (+/-SD) follow-up of 3.9 +/- 4.5 years (range,
1 day to 25 years), 10 patients (16%) recovered, 17 (27%) had residual
disease, 4 (6.4%) underwent heart transplantation, and 31 (50%) died.
Infants (<1 year of age) and adolescent (>/=15 years of age) male patients
with progressing symptoms of left ventricular failure after initiation
of medical therapy tended to have the poorest outcome. However, in multivariate
analysis, only histologic evidence of endocardial fibroelastosis, clinical
signs of right ventricular failure at presentation, and the need for
anticoagulative therapy during follow-up, the last an expression of
a severely impaired left ventricular systolic function, appeared to
be significant predictors of long-term outcome.
CONCLUSIONS: Our study confirms that the outcome of children with IDCM
still remains poor. However, a group of patients, mainly infants, make
a full recovery. Adolescent male patients as well as infants suffering
from endocardial fibroelastosis with persisting symptoms of congestive
heart failure after initiation of medical therapy tend to have the poorest
outcome. These patients need a careful follow-up at short time intervals
and, in the case of lacking response to medical treatment with resulting
growth failure and/or poor quality of life, should be offered urgent
heart transplantation.
|
|
Idiopathic dilated cardiomyopathy in children: clinical
profile and prognostic determinants.
Nogueira G, Pinto FF, Paixao A, Kaku S.
Servico de Cardiologia Pediatrica-Hospital de Santa
Marta.
|
Rev Port Cardiol 2000 Feb;19(2):191-200 Abstract quote
Idiopathic dilated cardiomyopathy is a severe disease with a high mortality
rate in childhood. Its clinical evolution and prognosis are important
for the selection of cardiac transplantation candidates.
In order to characterize its evolution and identify prognostic factors,
the clinical records of 41 children with the diagnosis of idiopathic
dilated cardiomyopathy, admitted from January 1985 to December 1997,
were reviewed. Survivors (Group I) and deceased (Group II) were separately
analyzed, according to the following parameters: age, sex, race, clinical
severity, electrocardiographic, echocardiographic and haemodynamic findings.
Seven children were excluded from the study: six of them were lost to
follow-up and one died from a surgical complication. Of the remaining
34 children, 20 were male (M) and 14 were female (F) (M/F: 1.4). Age
range at diagnosis was 7 days to 14 years (median: 1.5 years), and follow-up
time was from 18 days to 10.5 years (median: 2.5 years). Eleven (32.3%)
children fully recovered, 13 (38.2%) survived with left ventricular
dysfunction, and ten (29.4%) died, half of them within the first three
months of follow-up. Mortality was 23.5% (8 out of 34 children) during
the first year of follow-up and 29.4% (ten out of 34 children) at five
years.
Unfavorable prognosis was more frequently associated to: 1) clinical
severity at the time of presentation; 2) lower mean left ventricular
shortening fraction (10 +/- 7% in group II and 13 +/- 5% in group I);
3) occurrence of severe arrhythmia (40% in group II and 3.5% in group
I).
In this series a group of higher mortality risk was identified, based
on some of the analyzed parameters, which should be considered as selection
criteria for early heart transplantation.
|
| TREATMENT |
|
|
Poor survival of patients with idiopathic cardiomyopathy
considered too well for transplantation.
Stevenson LW, Fowler MB, Schroeder JS, Stevenson WG,
Dracup KA, Fond V.
Department of Medicine, UCLA Medical Center 90024-1679.
|
Am J Med 1987 Nov;83(5):871-6 Abstract quote
Although the success of cardiac transplantation has encouraged earlier
referral of potential candidates, those with mild symptoms of heart
failure are frequently considered "too well" for transplantation.
Outcome was investigated for 28 patients with non-ischemic dilated
cardiomyopathy and ejection fraction of 25 percent or less who were
denied transplantation due to lack of severe symptoms. One-year survival
without transplantation was 46 percent. Low stroke volume and history
of ventricular arrhythmias were independent predictors of early mortality.
High risk, defined as either stroke volume of 40 ml or less or history
of ventricular arrhythmia, identified 13 of 14 patients who did not
survive one year and only one of 12 one-year survivors (p less than
0.001). Low stroke volume predicted hemodynamic failure (p less than
0.05) whereas arrhythmic history predicted sudden death (p less than
0.001). Clinical status improved in only six patients, all of whom had
symptom duration of seven or less months at initial evaluation (p less
than 0.001).
Thus, patients referred to transplantation for dilated cardiomyopathy
with an ejection fraction of 25 percent or less have a poor prognosis
even if symptoms are mild. Patients with high hemodynamic risk may require
early transplantation, whereas those with high arrhythmia risk may require
other aggressive therapy in order to avoid transplantation until symptoms
become severe.
|
| DILATED |
|
-
Effect of Beta-Blocker Therapy on Myocardial Perfusion Defects in Thallium-201 Scintigraphy in Patients with Dilated Cardiomyopathy.
Hara Y, Inoue K, Ogimoto A, Ohtsuka T, Shigematsu Y, Nakata S, Higaki J.
Department of Internal Medicine, Ehime University School of Medicine, Toon City, Japan.
|
-
| Cardiology. 2005 May 28;104(1):16-21 [Epub ahead of print] Abstract quote |
|
Background: Thebeneficial effects of beta-blocker therapy in patients with heart failure have been confirmed. However, the effects of beta-blockers on myocardial perfusion defects are unclear.
The aim of this study was to evaluate the effect of beta-blockers on myocardial perfusion defects estimated by thallium-201 myocardial scintigraphy in patients with dilated cardiomyopathy (DCM) and to investigate the relationships between beta-blocker treatment and myocardial damage and cardiac function.
Methods:(201)Tl and echocardiography were performed in 37 patients before and after 6 months of beta-blocker therapy. Extent score (ES) by (201)Tl was used to quantitate myocardial perfusion defects before and after treatment.
Results: ES was significantly decreased by beta-blocker therapy. According to the change in ES, DCM patients were classified into three groups, patients who improved, patients showing no change and patients who deteriorated. In the improvement and no-change groups, beta-blocker therapy induced a reduction in left ventricular dimensions and an associated increase in ejection fraction. However, in the deterioration group, left ventricular dimensions and ejection fraction were unchanged. There was a significant relationship between the change in left ventricular dimension at end-diastole and the change in ES.
Conclusions: beta-Blocker therapy could attenuate myocardial perfusion defects in some patients with DCM. The improvement in left ventricular function associated with beta-blocker therapy may be related to the attenuation in myocardial perfusion defects.
|
|
The effect of treatment with angiotensin-converting
enzyme inhibitors on survival of pediatric patients with dilated cardiomyopathy.
Lewis AB, Chabot M.
Division of Cardiology, Childrens Hospital Los Angeles,
CA 90054-0700.
|
Pediatr Cardiol 1993 Jan;14(1):9-12 Abstract quote
Outcome in 81 pediatric patients with dilated cardiomyopathy was reviewed
to assess whether treatment with angiotensin-converting enzyme (ACE)
inhibitors affected survival.
Age at onset was 3.6 +/- 0.6 years. Twenty-seven children (group 1)
were treated with ACE inhibitors. Conventional therapy was used in the
remaining 54 patients (group 2). There were no significant differences
between the two groups in age at onset, left ventricular shortening
fraction, left ventricular end-diastolic pressure, or mean pulmonary
artery pressure. Patients treated with ACE inhibitors had a significantly
better survival during the first year (p < 0.05) with continuation of
this trend throughout the second year (p = 0.06). Beyond 2 years there
was a tendency toward better survival in ACE inhibitor-treated patients,
but the differences were no longer significant (p = 0.14).
These data, along with observations in adult patients with chronic
cardiac failure, indicate that converting enzyme inhibitors have a beneficial
effect on prolonging survival of infants and children with severe left
ventricular dysfunction from dilated cardiomyopathy.
|
|
Changing mortality in dilated cardiomyopathy. The
Heart Muscle Disease Study Group.
Di Lenarda A, Secoli G, Perkan A, Gregori D, Lardieri
G, Pinamonti B, Sinagra G, Zecchin M, Camerini F.
Department of Cardiology, Ospedale Maggiore and University,
Trieste, Italy.
|
Br Heart J 1994 Dec;72(6 Suppl):S46-51 Abstract quote
OBJECTIVE--To analyse the changes in mortality in dilated cardiomyopathy
over the past 15 years and to identify the factors that might have influenced
survival. DESIGN--Follow up study of 235 patients (aged 16-70) systematically
enrolled on a register from 1 January 1978 to 31 December 1992.
SETTING--Hospital department of cardiology.
PATIENTS--Three groups corresponding to three periods of 5 years: group
1 (diagnosis between 1 January 1978 and 31 December 1982) 26 patients;
group 2 (diagnosis between 1 January 1983 and 31 December 1987) 65 patients;
and group 3 (diagnosis between 1 January 1988 and 31 December 1992)
144 patients.
MAIN OUTCOME MEASURES--Death or heart transplantation.
RESULTS--Two and four year survival was 73.8% and 53.8% in group 1,
87.7% and 72.3% in group 2, and 90.3% and 82.9% in group 3 (P = 0.02).
During the 15 years of the study period the number of cases increased
progressively and the baseline clinical characteristics changed (that
is, patients were younger and less severely affected), partly explaining
the improvement in survival. None the less, the three mortality curves
tended to diverge progressively and the improvement in survival in the
different groups was still significant after stratification for the
severity of the disease, suggesting that treatment had a sustained effect.
A progressively higher proportion of patients were treated with angiotensin
converting enzyme (ACE) inhibitors and more recently with beta blockers.
In group 2, after stratification for the severity of heart failure,
patients who were treated with ACE inhibitors showed a better survival
than patients who were not. Furthermore, analysis of group 3 showed
that beta blockers had a significant additive effect with conventional
therapy both by intention to treat and actual treatment. Four year survival
in patients with mild and moderate to severe heart failure treated with
beta blockers, and usually digitalis and ACE inhibitors, was respectively
90% and 87.5%.
CONCLUSIONS--The improvement in the survival of patients with dilated
cardiomyopathy over the past 15 years may be explained by earlier diagnosis,
new treatments, and a change in the clinical characteristics of the
patients at enrolment.
|
|
Long-term survival effect of metoprolol in dilated
cardiomyopathy. The SPIC (Italian Multicentre Cardiomyopathy Study)
Group.
Di Lenarda A, De Maria R, Gavazzi A, Gregori D, Parolini
M, Sinagra G, Salvatore L, Longaro F, Bernobich E, Camerini F.
Department of Cardiology, Ospedale Maggiore and University,
Trieste, Italy.
|
Heart 1998 Apr;79(4):337-44 Abstract quote
OBJECTIVE: To evaluate the additive effect of metoprolol treatment
on long-term incidence of fatal and non-fatal cardiac events in idiopathic
dilated cardiomyopathy.
DESIGN: 586 patients with idiopathic dilated cardiomyopathy were prospectively
enrolled in a multicentre registry and followed up for a mean (SD) of
52 (32) months. Metoprolol, carefully titrated to the maximum tolerated
dose, was added to conventional heart failure treatment in 175 patients.
RESULTS: Survival and transplant-free survival at seven years were
significantly higher in the 175 metoprolol treated patients than in
the remaining 411 on standard treatment (81% v 60%, p < 0.001, and 69%
v 49%, p < 0.001, respectively). By multivariate analysis, metoprolol
independently predicted survival and transplant-free survival (relative
risk reduction values for all cause mortality and combined mortality
or transplantation 51% (95% confidence interval 21% to 69%), p = 0.002,
and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association
class, left ventricular end diastolic diameter, and pulmonary wedge
pressure were also predictive. Seven year survival (80% v 62%, p = 0.004)
and transplant-free survival (68% v 51%, p = 0.005) were significantly
higher in 127 metoprolol treated cases than in 127 controls selected
from the entire control cohort and appropriately matched. Metoprolol
was associated with a 30% reduction in all cause mortality (7% to 48%,
p = 0.015) and a 26% reduction in mortality or transplantation (7% to
41%, p = 0.009).
CONCLUSIONS: The addition of metoprolol to standard heart failure treatment,
including angiotensin converting enzyme inhibitors, was effective in
the long-term, reducing both all cause mortality and transplantation
in patients with idiopathic dilated cardiomyopathy.
|
|
Outcomes for children with cardiomyopathy awaiting
transplantation.
Nield LE, McCrindle BW, Bohn DJ, West LJ, Coles JG,
Freedom RM, Benson LN.
Department of Paediatrics, The Hospital for Sick Children,
The University of Toronto School of Medicine, Ontario, Canada.
|
Cardiol Young 2000 Oct;10(4):358-66 Abstract quote
OBJECTIVE: To determine factors associated with outcomes after listing
for transplantation in children with cardiomyopathies.
BACKGROUND: Childhood cardiomyopathies form a heterogeneous group of
diseases, and in many, the prognosis is poor, irrespective of the etiology.
When profound heart failure develops, cardiac transplantation can be
the only viable option for survival.
METHODS: We included all children with cardiomyopathy listed for transplantation
between 12/89 and 4/98 in this historical cohort study.
RESULTS: We listed 31 patients, 15 male and 16 female, 27 with dilated
and 4 with restrictive cardiomyopathy, for transplantation. The median
age at listing was 5.7 years, with a range from fetal life to 17.8 years.
Transplantation was achieved in 23 (74%), with a median interval from
listing of 54 days, and a range from zero to 11.4 years. Of the patients,
14 were transplanted within 30 days of listing. Five patients (16%)
died before transplantation. Within the Canadian algorithm, one of these
was in the third state, and four in the fourth state. One patient was
removed from the list after 12 days, having recovered from myocarditis,
and two remain waiting transplantation after intervals of 121 and 476
days, respectively. Patients who died were more likely to be female
(5/5 vs. 11/26; p=0.04) and to have been in the third or fourth states
at listing (5/5 vs. 15/26; p=0.04). The use of mechanical ventricular
assistance, in 10 patients, was not a predictor of an adverse outcome.
While not statistically significant, survival to transplantation was
associated with treatment using inhibitors of angiotensin converting
enzyme, less mitral regurgitation, a higher mean ejection fraction and
cardiac index, and lower right ventricular systolic pressure.
CONCLUSIONS: Children with cardiomyopathy awaiting transplantation
have a mortality of 16% related to their clinical state at the time
of listing.
|
|
Surgical approaches to dilated cardiomyopathy.
Smolens IA, Bolling SF.
Section of Cardiac Surgery, University of Michigan,
Taubman Health Care Center, 2120D, Box 0348, 1500 East Medical Center
Drive, Ann Arbor, MI 48109-0348, USA.
|
Curr Cardiol Rep 2000 Mar;2(2):99-105 Abstract quote
Heart failure is one of the leading causes of hospitalization in the
United States today. Congestive heart failure is a chronic progressive
disease with the common central element being the remodeling of the
cardiac chamber associated with ventricular dilation. Secondary mitral
regurgitation is a complication of end-stage cardiomyopathy and is associated
with a poor prognosis. Historically, these patients were not considered
operative candidates due to the high morbidity and mortality in this
patient population.
Heart transplantation is now considered the standard of treatment for
select patients with end-stage heart disease, however, it is only applicable
to a small number of patients. In an effort to address this problem,
newer and alternative surgical approaches are evolving, including mitral
valve annuloplasty, the Batista myoplasty, and cardiomyoplasty.
When these operative techniques that alter the shape of the left ventricle
are utilized, in combination with optimal medical management for heart
failure, survival is improved and patients can avoid or postpone transplantation.
|
|
Outcome while awaiting heart transplantation in children:
a comparison of congenital heart disease and cardiomyopathy.
Rosenthal DN, Dubin AM, Chin C, Falco D, Gamberg
P, Bernstein D.
Department of Pediatricsa, Lucile Salter Packard Children's
Hospital and Stanford University Hospital, Stanford University, Stanford,
California, USA.
|
J Heart Lung Transplant 2000 Aug;19(8):751-5 Abstract quote
BACKGROUND: Outcomes for children who undergo heart transplantation
differ for children with congenital heart disease as compared to those
with structurally normal hearts. Similar data have not been reported
for these groups of patients for the morbidity and mortality associated
with waiting for a donor. We report these data.
METHODS: A retrospective review was performed for all pediatric patients
who were listed for heart transplantation at Stanford from 1977 to 1996,
comparing mortality and major morbidity for patients with congenital
heart disease and those with cardiomyopathy and structurally normal
hearts.
RESULTS: There were 96 patients who met study criteria, of whom 67
were successfully transplanted. The median waiting time was 23 days.
Survival at 30 days was 93% and at 90 days was 81%, with no difference
between groups. Major complications were identified in 38% of patients
with structurally normal hearts, vs 9% of patients with congenital heart
disease (p < 0.001).
CONCLUSIONS: Overall mortality is similar for patients with congenital
heart disease and those with structurally normal hearts while listed
for heart transplantation, but patients with congenital heart disease
have fewer episodes of major morbidity during this time.
|
|
Impact of cardiac transplantation on molecular pathology
of ET-1, VEGF-C, and mitochondrial metabolism and morphology in dilated
versus ischemic cardiomyopathic patients.
Aharinejad S, Schafer R, Hofbauer R, Abraham D, Blumer
R, Miksovsky A, Traxler H, Pullirsch D, Alexandrowicz R, Taghavi S,
Kocher A, Laufer G.
Laboratory for Cardiovascular Research, First Department
of Anatomy, University of Vienna, Waehringerstrasse 13, A-1090 Vienna,
Austria.
|
Transplantation 2001 Sep 27;72(6):1043-9 Abstract quote
Little is known about the long-term impact of cardiac transplantation
on activity and modifications of endothelin (ET)-1 system, vascular
endothelial growth factor (VEGF), and mitochondrial metabolism and morphology
in patients with ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy
(DCM).
Messenger RNA (mRNA) expression levels of ET-1, endothelin converting
enzyme (ECE)-1, VEGF-C, carnitine palmitoyltransferase (CPT)-1, and
carnitine acetyltransferase (CARAT), as well as the number of normal,
edematous, and degenerated mitochondria were assessed in left ventricular
biopsies of 21 patients with DCM and 20 with ICM (New York Heart Association
class III-IV) before and up to 3 months after cardiac transplantation.
|
