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Created page with "Cardiomyopathy in HIV patients -=ETIOLOGY== The pathophysiology of HIV cardiomyopathy is unclear but is probably multifactorial. Some patients with asymptomatic or overt LV dy..."
Cardiomyopathy in HIV patients
-=ETIOLOGY==
The pathophysiology of HIV cardiomyopathy is unclear but is probably multifactorial.
Some patients with asymptomatic or overt LV dysfunction have a known or clear
etiology such as CAD, cocaine use, EtOH heart disease, drug toxicity, or myocarditis
due to an OI such as toxo or crypto [1,2,41]. The endothelium is a reservoir for HIV
and produces cytokines such as TNF, IL-6, and free radicals in response to
inflammation that in turn causes myocardial dysfunction. Direct infection of
myocardial cells by HIV, while possible, is controversial, since cardiac myocytes
lack HIV-1 receptor proteins (gp120 or gp24) [42]. Other possible causes of
myocardial dysfunction include mitochondrial damage from certain antiretroviral
agents, such as NRTIs [42].
==-Ischemia===
In a study of 608 patients with HIV hospitalized for an acute MI in France, the
prevalence of ischemic cardiomyopathy was higher compared with 1216 uninfected
controls matched for age and gender (7.6% vs 4.2%) [45]. Although in-hospital and
one-year mortality rates were similar in both groups, patients with HIV were more
likely to be rehospitalized for CHF during that year than the controls (3.3% vs
1.4%)。
===Myocarditis==s
Although HIV has been identified in myocardial biopsies from patients with HIV
cardiomyopathy [46], the virus may have been in blood or endothelial cells rather
than in myocardial cells. Other cardiotropic viruses that are not directly
identified, such as CMV, coxsackie, or EBV, also may be important (7,25,41].
Additionally, a dysregulated inflammatory process induced by HIV or other
cardiotropic viruses may also contribute.
In a South African study in which 14 patients with HIV-associated cardiomyopathy
underwent endomyocardial biopsy, myocarditis was identified in 44% and a
cardiotropic virus was identified in all [25]. The most common were EBV, HSV, and
HIV.
Other infectious etiologies that have been implicated in CM associated with HIV
infection include coxsackie [22,40,47], CMV [22,40,48], and Crypto [49].
whether direct infection of the heart by HIV contributes to development of
myocarditis in patients with end-stage HIV disease is unclear, but some studies
suggest that it is possible. Since the myocardial cell lacks CD4 receptors, HIV is
denied the usual mode of entrance into the cell. However, the organism could enter
the cell if the cell was injured by another virus. In in vitro studies, for example,
EBV permitted the entrance and replication of HIV into CD4 receptor-negative
myocardial cells [52].
===Cardiotoxic Agents===
In addition to direct effects of cocaine on the heart as well as indirect effects
Cardiotoxicity from therapeutic drugs such as pentamidine (72] and possibly
zidovudine (73] may contribute to the development of cardiomyopathy in patients with
HIV. Zidovudine produces cardiomyopathy in mice with pathologic changes in the
mitochondria [1,74]. Patients with HIV and cardiomyopathy have been reported on
myocardial biopsy to have similar ultrastructural changes in their mitochondria.
==EPIDEMIOLOGY==
HIV infection has been associated with an increased risk of CHF in the ART era [17).
In the Veterans Aging Cohort Study, which followed 98,015 patients without baseline
CVD for a median of 7.1 years, veterans with HIV had an increased risk of HFrEF
(hazard ratio [HR] 1.61, 95% CI 1.40-1.86) and MFpEF (HR 1.37, 95% CI 1.09-1.72)
compared with matched seronegative veterans. The risk of HFrEF was associated with
high HIV viral loads (› 500 copies/mL) and low CD4 cell counts (< 20/mm3), and it
was pronounced in veterans younger than 40 years at baseline (HR 3.59, 95% CI
1.95-6.58).
By contrast, pericardial effusion and myocardial disease, such as myocarditis and
cardiomyopathy which were frequently reported among patients with HIV before the
widespread use of ART, particularly in the setting of significant immunosuppression,
are increasingly uncommon. However, in resource-limited settings, where many
patients have limited access to ART, these syndromes remain the most common
manifestations of HIV-associated cardiac disease (18,19). In a study of 5328
patients presenting with a first diagnosis of heart disease to a large cardiology
center in South Africa, 518 (10%) had HIV, among whom cardiomyopathy was diagnosed
in 38% (86% of whom reported some level of symptoms and functional limitation),
pericarditis in 13% [19], and CAD in 2.7%. This pattern may change as the use of ART
worldwide has been increasing.
-CLINICAL PRESENTATIONRE
The clinical presentation of cardiomyopathy is similar in patients with HIV as in
those who are not infected. The initial symptoms are nonspecific: as an example,
dyspnea may be due to pulmonary involvement or cardiac disease. More specific signs
of cardiac involvement are an $3 gallop or pulmonary edema or a pathologic murmur.
*DIAGNOSISse
The diagnosis of cardiomyopathy in patients with HIV, as in the general population,
Is made through the finding of characteristic abnormalities on electrocardiography,
chest radiograph, and echocardiography in the setting of symptoms and signs
SuRgestive of heart failure.
*-TREATMENTee
The treatment of the patient with HIV and symptomatic cardiomyopathy is similar to
that in the general population and involves pharmacologic management of heart
failure with diuretics, angiotensin-converting enzyme (ACE) inhibitors, and beta
HIV DCM
blockers. There are limited data on the efficacy of these interventions in the
setting of HIV infection, so the efficacy is extrapolated from evidence in the
general population.
Correction of any identified underlying cause of the cardiomyopathy is warranted.
As
an example, drugs that have been implicated in cardiomyopathy should be
discontinued. Additionally, with increasing evidence that patients with HIV,
especially those on ART regimens, have an increased risk of atherosclerotic disease,
including coronary artery disease, special attention to eliminating conventional
cardiovascular risk factors such as smoking, controlling hypertension and diabetes,
statin use, and reducing weight in overweight patients is important.
There is no definite direct evidence that ART leads to an improvement in
cardiomyopathy, although the decline in the prevalence of HIV-associated
cardiomyopathy following the introduction of potent ART in resource-rich settings
suggest a benefit.
"Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of
HIV-positive Patients"
NEJM, 1998
Barbaro G, Di Lorenzo G, Girsori B, Barbarini G
BACKGROUND - HIV infection is increasingly recognized as an important cause of DCM.
However, the pathogenesis of the heart-muscle disease in AIDS is unclear.
METHODS
- We performed a prospective, long-term clinical and echocardiographic
follow-up study of 952 asymptomatic HIV-positive patients to assess the incidence of
CM and to analyze the clinical variables associated with the development of
cardiomyopathy. All patients with an echocardiographic diagnosis of CM underwent
endomyocardial biopsy for histologic, immunohistologic, and virologic assessment.
RESULTS -- During a mean (+/-SD) follow-up period of 60+/-5.3 months, an
echocardiographic diagnosis of DCM was made in 76 patients (8%), with a mean annual
incidence rate of 15.9 cases per 1000 patients. The incidence of DCM was higher in
patients with a CD4+ count < 400 and in those who received therapy with zidovudine.
A histologic diagnosis of myocarditis was made in 63 of the patients with DCM (83%)
Inflammatory infiltrates were predominantly composed of CD3 and CD8 lymphocytes,
with staining for MHC-I antigens in 71% of the patients. In the myocytes of 58
patients, HIV nucleic acid sequences were detected by ISH, and active myocarditis
was documented in 36 of the 58. Among these 36 patients, 6 were also infected with
coxsackievirus group B (17%), 2 with cytomegalovirus (6%), and 1 with Epstein-Barr
virus (3%).
CONCLUSIONS -- DCM may be related either to a direct action of HIV on the myocardial
tissue or to an autoimmune process induced by HIV, possibly in association with
other cardiotropic viruses.
-=ETIOLOGY==
The pathophysiology of HIV cardiomyopathy is unclear but is probably multifactorial.
Some patients with asymptomatic or overt LV dysfunction have a known or clear
etiology such as CAD, cocaine use, EtOH heart disease, drug toxicity, or myocarditis
due to an OI such as toxo or crypto [1,2,41]. The endothelium is a reservoir for HIV
and produces cytokines such as TNF, IL-6, and free radicals in response to
inflammation that in turn causes myocardial dysfunction. Direct infection of
myocardial cells by HIV, while possible, is controversial, since cardiac myocytes
lack HIV-1 receptor proteins (gp120 or gp24) [42]. Other possible causes of
myocardial dysfunction include mitochondrial damage from certain antiretroviral
agents, such as NRTIs [42].
==-Ischemia===
In a study of 608 patients with HIV hospitalized for an acute MI in France, the
prevalence of ischemic cardiomyopathy was higher compared with 1216 uninfected
controls matched for age and gender (7.6% vs 4.2%) [45]. Although in-hospital and
one-year mortality rates were similar in both groups, patients with HIV were more
likely to be rehospitalized for CHF during that year than the controls (3.3% vs
1.4%)。
===Myocarditis==s
Although HIV has been identified in myocardial biopsies from patients with HIV
cardiomyopathy [46], the virus may have been in blood or endothelial cells rather
than in myocardial cells. Other cardiotropic viruses that are not directly
identified, such as CMV, coxsackie, or EBV, also may be important (7,25,41].
Additionally, a dysregulated inflammatory process induced by HIV or other
cardiotropic viruses may also contribute.
In a South African study in which 14 patients with HIV-associated cardiomyopathy
underwent endomyocardial biopsy, myocarditis was identified in 44% and a
cardiotropic virus was identified in all [25]. The most common were EBV, HSV, and
HIV.
Other infectious etiologies that have been implicated in CM associated with HIV
infection include coxsackie [22,40,47], CMV [22,40,48], and Crypto [49].
whether direct infection of the heart by HIV contributes to development of
myocarditis in patients with end-stage HIV disease is unclear, but some studies
suggest that it is possible. Since the myocardial cell lacks CD4 receptors, HIV is
denied the usual mode of entrance into the cell. However, the organism could enter
the cell if the cell was injured by another virus. In in vitro studies, for example,
EBV permitted the entrance and replication of HIV into CD4 receptor-negative
myocardial cells [52].
===Cardiotoxic Agents===
In addition to direct effects of cocaine on the heart as well as indirect effects
Cardiotoxicity from therapeutic drugs such as pentamidine (72] and possibly
zidovudine (73] may contribute to the development of cardiomyopathy in patients with
HIV. Zidovudine produces cardiomyopathy in mice with pathologic changes in the
mitochondria [1,74]. Patients with HIV and cardiomyopathy have been reported on
myocardial biopsy to have similar ultrastructural changes in their mitochondria.
==EPIDEMIOLOGY==
HIV infection has been associated with an increased risk of CHF in the ART era [17).
In the Veterans Aging Cohort Study, which followed 98,015 patients without baseline
CVD for a median of 7.1 years, veterans with HIV had an increased risk of HFrEF
(hazard ratio [HR] 1.61, 95% CI 1.40-1.86) and MFpEF (HR 1.37, 95% CI 1.09-1.72)
compared with matched seronegative veterans. The risk of HFrEF was associated with
high HIV viral loads (› 500 copies/mL) and low CD4 cell counts (< 20/mm3), and it
was pronounced in veterans younger than 40 years at baseline (HR 3.59, 95% CI
1.95-6.58).
By contrast, pericardial effusion and myocardial disease, such as myocarditis and
cardiomyopathy which were frequently reported among patients with HIV before the
widespread use of ART, particularly in the setting of significant immunosuppression,
are increasingly uncommon. However, in resource-limited settings, where many
patients have limited access to ART, these syndromes remain the most common
manifestations of HIV-associated cardiac disease (18,19). In a study of 5328
patients presenting with a first diagnosis of heart disease to a large cardiology
center in South Africa, 518 (10%) had HIV, among whom cardiomyopathy was diagnosed
in 38% (86% of whom reported some level of symptoms and functional limitation),
pericarditis in 13% [19], and CAD in 2.7%. This pattern may change as the use of ART
worldwide has been increasing.
-CLINICAL PRESENTATIONRE
The clinical presentation of cardiomyopathy is similar in patients with HIV as in
those who are not infected. The initial symptoms are nonspecific: as an example,
dyspnea may be due to pulmonary involvement or cardiac disease. More specific signs
of cardiac involvement are an $3 gallop or pulmonary edema or a pathologic murmur.
*DIAGNOSISse
The diagnosis of cardiomyopathy in patients with HIV, as in the general population,
Is made through the finding of characteristic abnormalities on electrocardiography,
chest radiograph, and echocardiography in the setting of symptoms and signs
SuRgestive of heart failure.
*-TREATMENTee
The treatment of the patient with HIV and symptomatic cardiomyopathy is similar to
that in the general population and involves pharmacologic management of heart
failure with diuretics, angiotensin-converting enzyme (ACE) inhibitors, and beta
HIV DCM
blockers. There are limited data on the efficacy of these interventions in the
setting of HIV infection, so the efficacy is extrapolated from evidence in the
general population.
Correction of any identified underlying cause of the cardiomyopathy is warranted.
As
an example, drugs that have been implicated in cardiomyopathy should be
discontinued. Additionally, with increasing evidence that patients with HIV,
especially those on ART regimens, have an increased risk of atherosclerotic disease,
including coronary artery disease, special attention to eliminating conventional
cardiovascular risk factors such as smoking, controlling hypertension and diabetes,
statin use, and reducing weight in overweight patients is important.
There is no definite direct evidence that ART leads to an improvement in
cardiomyopathy, although the decline in the prevalence of HIV-associated
cardiomyopathy following the introduction of potent ART in resource-rich settings
suggest a benefit.
"Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of
HIV-positive Patients"
NEJM, 1998
Barbaro G, Di Lorenzo G, Girsori B, Barbarini G
BACKGROUND - HIV infection is increasingly recognized as an important cause of DCM.
However, the pathogenesis of the heart-muscle disease in AIDS is unclear.
METHODS
- We performed a prospective, long-term clinical and echocardiographic
follow-up study of 952 asymptomatic HIV-positive patients to assess the incidence of
CM and to analyze the clinical variables associated with the development of
cardiomyopathy. All patients with an echocardiographic diagnosis of CM underwent
endomyocardial biopsy for histologic, immunohistologic, and virologic assessment.
RESULTS -- During a mean (+/-SD) follow-up period of 60+/-5.3 months, an
echocardiographic diagnosis of DCM was made in 76 patients (8%), with a mean annual
incidence rate of 15.9 cases per 1000 patients. The incidence of DCM was higher in
patients with a CD4+ count < 400 and in those who received therapy with zidovudine.
A histologic diagnosis of myocarditis was made in 63 of the patients with DCM (83%)
Inflammatory infiltrates were predominantly composed of CD3 and CD8 lymphocytes,
with staining for MHC-I antigens in 71% of the patients. In the myocytes of 58
patients, HIV nucleic acid sequences were detected by ISH, and active myocarditis
was documented in 36 of the 58. Among these 36 patients, 6 were also infected with
coxsackievirus group B (17%), 2 with cytomegalovirus (6%), and 1 with Epstein-Barr
virus (3%).
CONCLUSIONS -- DCM may be related either to a direct action of HIV on the myocardial
tissue or to an autoimmune process induced by HIV, possibly in association with
other cardiotropic viruses.