This document summarizes various cardiovascular manifestations that can occur in systemic diseases. It discusses how thiamine deficiency can cause heart failure and how supplementation can help. It also discusses protein-energy malnutrition and how it can affect the heart. Other conditions mentioned include hyperhomocysteinemia, obesity, carcinoid syndrome, pheochromocytoma, acromegaly, systemic lupus erythematosus, antiphospholipid antibody syndrome, systemic sclerosis, and rheumatoid arthritis; and their potential impacts such as cardiomyopathy, pericarditis, accelerated atherosclerosis, and pulmonary hypertension.

1. CARDIOVASCULAR manifestation in systemic
disease
Dr. ANIL KHATRI

3. THIAMINE
• Thiamine deficiency in where polished rice
use, chronic alcoholics, after chemotherapy
etc.
• thiamine deficiency has been found in 20–90%
of patients with chronic heart failure. This
deficiency appears to result from both
reduced dietary intake and a diuretic-induced
increase in the urinary excretion of thiamine.
• The acute administration of thiamine to these
patients increases the left ventricular ejection
fraction and the excretion of salt and water.

4. • The classic associated cardiovascular
syndrome is characterized by high-output
heart failure, tachycardia, and often elevated
biventricular filling pressures. The major cause
of the high-output state is vasomotor
depression leading to reduced systemic
vascular resistance, the precise mechanism of
which is not understood.
• The cardiac examination may reveal a wide
pulse pressure, tachycardia, a third heart
sound, and an apical systolic murmur.

5. • The electrocardiogram (ECG) may reveal decreased
voltage, a prolonged QT interval, and T-wave
abnormalities.
• The chest x-ray generally reveals cardiomegaly and
signs of congestive heart failure (CHF).
• The response to thiamine is often dramatic, with an
increase in systemic vascular resistance, a decrease
in cardiac output, clearing of pulmonary congestion,
and a reduction in heart size often occurring in
12–48 h.
• Although the response to inotropes and diuretics
may be poor before thiamine therapy, these agents
may be important after thiamine repletion.

6. PEM
• In patients whose intake of protein, calories,
or both is severely deficient, the heart may
become thin, pale, and hypokinetic with
myofibrillar atrophy and interstitial edema.
• Generalized edema is common and relates to
a variety of factors, including reduced serum
oncotic pressure and myocardial dysfunction.
• Open-heart surgery poses increased risk in
malnourished patients.

7. HYPERHOMOCYSTEINEMIA
• Vitamin B6 , vitamin B12, and folate are cofactors
in the metabolism of homocysteine. Their
deficiency probably contributes to the majority of
cases of hyperhomocysteinemia, a disorder
associated with increased atherosclerotic risk.
• Supplementation of these vitamins has reduced
the incidence of hyperhomocysteinemia, however
the clinical cardiovascular benefit of normalizing
elevated homocysteine levels has not been
proved. (inhibit the formation artery, collagen,
proteoglycans)

8. OBESITY
• Obesity is associated with an increased
prevalence of hypertension, glucose
intolerance, atherosclerotic CAD, atrial
fibrillation, obstructive sleep apnea, and
pulmonary hypertension, and is associated
with increased cardiovascular morbidity and
mortality rates.
• In addition, obese patients have a distinct
hemodynamic profile characterized by
increased total and central blood volumes,
increased cardiac output, and elevated left
ventricular filling pressure

9. • In part as a result of chronic volume overload,
eccentric cardiac hypertrophy with cardiac dilation
and ventricular diastolic and/or systolic dysfunction
may develop.
• In addition, altered levels of adipokines secreted by
adipose tissue may contribute to adverse
myocardial remodeling via direct effects on cardiac
myocytes and other cells.

10. • Treatment with angiotensin-converting enzyme
inhibitors, sodium restriction, and diuretics may be
useful to control heart failure symptoms.
• Weight reduction, however, is the most effective
therapy and results in reduction in blood volume
and the return of cardiac output toward normal.
However, rapid weight reduction may be dangerous,
as cardiac arrhythmias and sudden death owing to
electrolyte imbalance have been described.

11. MALIGNANT CARCINOID
• Carcinoid tumors most often originate in the
small bowel and elaborate a variety of
vasoactive amines (e.g., serotonin), kinins,
indoles, and prostaglandins that are believed
to be responsible for the diarrhea, flushing,
and labile blood pressure that characterize the
carcinoid syndrome.
• Some 50% of patients with carcinoid
syndrome have cardiac involvement, usually
manifesting as abnormalities of the tricuspid
or pulmonic valves.

12. • Pathologically, carcinoid lesions are fibrous plaques
that consist of smooth-muscle cells embedded in a
stroma of glycosaminoglycans and collagen. They
occur on the cardiac valves, where they cause
valvular dysfunction, as well as on the endothelium
of the cardiac chambers and great vessels.
• Carcinoid heart disease most often presents as
tricuspid regurgitation, pulmonic stenosis, or both.
In some cases, a high cardiac output state may
occur, presumably as a result of a decrease in
systemic vascular resistance resulting from
vasoactive substances released by the tumor.

13. • Treatment with somatostatin analogues (e.g.,
octreotide) or interferon α improves symptoms and
survival in patients with carcinoid heart disease but
does not appear to improve valvular abnormalities.
• In some severely symptomatic patients, valve
replacement is indicated.
• Coronary artery spasm, presumably due to a
circulating vasoactive substance, may occur in
patients with carcinoid syndrome.

14. PHEOCHROMOCYTOMA
• In addition to causing labile or sustained
hypertension, the high circulating levels of
catecholamines resulting from a
pheochromocytoma may cause direct myocardial
injury.
• Focal myocardial necrosis and inflammatory cell
infiltration are present in ~50% of patients who die
with pheochromocytoma and may contribute to
clinically significant left ventricular failure and
pulmonary edema.
• Left ventricular dysfunction and CHF may resolve
after removal of the tumor.

15. ACROMEGALY
• Exposure of the heart to excessive growth hormone
may cause CHF as a result of high cardiac output,
diastolic dysfunction owing to ventricular
hypertrophy global systolic dysfunction.
• Hypertension occurs in up to one-third of patients
with acromegaly and is characterized by
suppression of the renin-angiotensin-aldosterone
axis and increases in total-body sodium and plasma
volume.
• Some form of cardiac disease occurs in about one-
third of patients with acromegaly and is associated
with a doubling of the risk of cardiac death.

16. SLE
• Damage by tissue-binding autoantibodies and
immune complexes
• A multigenic disease
• More common in women and can occur at any
age.
• Diagnosis of SLE is based on characteristic clinical
features and autoantibodies.
• SLE may involve one or several organ systems;
over time, additional manifestations may occur

17. Cardiovascular Manifestations
• Pericarditis is the most commonly recognized
cardiac problem[30%]
• Coronary arteritis, resulting in ischemic
syndromes, rarely occur.
• In SLE, myocardial infarctions are primarily
manifestations of accelerated atherosclerosis.
• Risk factors for accelerated atherosclerosis
include disease duration, period of time treated
with corticosteroids, postmenopausal status and
hypercholesterolemia.

18. • Additional causes of ACS in SLE include
thrombosis, often related to the presence of
APLA, and embolism from Libman-Sacks.
• Valvular pathology in SLE is common.
• PAH can occur
• Pericardial effusion , myocarditis & arrythmias
are rare.
• Babies born to mothers with SLE and have an
increased incidence of congenital complete AV
block.

19. Antiphospholipid Antibody Syndrome
• Defined as the presence of either APLA or a lupus
anticoagulant and a history of otherwise unexplained
recurrent venous or arterial thrombosis, or frequent
second or third trimester miscarriages.
• Cardiac manifestations include thrombotic CAD,
intracardiac thrombi, and NBE.
• Heart valve abnormalities occur in approximately 30
percent of patients with primary APLAS and include
leaflet thickening, thrombotic masses extending from
the valve ring or leaflets, or vegetations.

20. • Pulmonary hypertension can occur in patients
with APLA secondary to chronic
thromboembolic disease. APLA may promote
pulmonary artery intimal proliferation.

21. Systemic sclerosis
• Chronic systemic disorder of unknown
etiology.
• Early stage → prominent inflammation,
followed by widespread functional and
structural alterations in multiple vascular beds
and progressive visceral organ dysfunction
due to fibrosis.
• Mainly 2 subtypes

22. • Pericardial involvement is common in PSS, and
includes fibrinous pericarditis in up to 70
percent of patients at autopsy.
• The presence of moderate or large pericardial
effusions is an independent risk factor for
mortality.
• Cardiac involvement in SSc may be due to
ischemic damage, myocarditis, replacement
fibrosis, systemic hypertension, and PAH.
• Myocardial involvement may be due to
myocardial ischemia, fibrosis, and myocarditis.

23. • Ventricular conduction abnormalities are
common and, along with a septal pseudo-infarct
pattern (q wave inversion in ecg mimic mi due to
elongation and partial stretching of cardiac nerve
fibres) , correlate with reduced myocardial
function with exercise.
• Renal crisis may be associated with minimal or
extreme hypertension, rapidly rising creatinine
level, microangiopathy, thrombocytopenia, and
left ventricular failure.
• Pulmonary hypertension occurs in both limited
scleroderma and PSS
• Outcome in SSc-associated PAH is considerably
worse.

24. Rheumatoid Arthritis
• Most common form of chronic inflammatory
polyarthritis
• Chronic symmetrical polyarthritis that affects
small and large joints
• Affects pericardium mostly. Chronic,
asymptomatic effusive pericardial disease is more
common
• Does not usually cause clinically significant
myocarditis but CHF seen with increased
prevelance

25. • Secondary amyloidosis – rare, It can cause
cardiomyopathy & AV block.
• Potential risk factors for CAD in patients with
RA - the chronic systemic inflammatory state,
generation of proatherosclerotic LDL forms,
use of selective or nonselective NSAIDs, under-
usage of aspirin, and use of steroids, which
may accelerate atherosclerosis.
• Coronary arteritis & valve involvement - rarely
reported

26. Ankylosing spondylitis
• Chronic inflammatory disease of unknown
cause associated HLA-B27
• TNFα - plays a central role in the immuno-
pathogenesis of AS.
• Features - Low back pain and stiffness,
enthesitis, chest pain, joint involvement,
uveitis, slowly progressive fibrosis of the
upper lobes of the lungs, neurological
syndromes, renal involvement & osteoporosis

27. • Aortic root disease- reported in up to 100
percent of AS patients who also had aortic
valve involvement in an autopsy series.
Characteristic findings - thickening of the
aortic root with subsequent dilation. Aortic
cusp nodularity with proximal thickening seen.
• Cardiac conduction disease has been well
described & more common in males
• Pericarditis & CAD rare.

28. Polymyositis and Dermatomyositis
• Localized or generalized myocardial
dysfunction is common by echocardiographic
assessment, but infrequently causes clinical
failure.
• The cardiomyopathy may be steroid-
responsive.
• PM and dermatomyositis frequently affect the
conduction system.

29. Sarcoidosis
• Granulomatous inflammatory disease of
unknown cause.
• Pericarditis though uncommon – usually
clinically insignificant
• Granulomatous infiltrative disease of the
myocardium is often asymptomatic, but can
cause arrhythmias, conduction disease and,
rarely, otherwise unexplained congestive
heart failure

30. • Pulmonary artery hypertension and cor
pulmonale can occur in sarcoidosis, generally
as a result of pulmonary fibrosis.
• Systemic vasculitis - an uncommon
complication of sarcoidosis.
• Sarcoid vasculitis can affect small- to large-
caliber vessels, including the aorta.

31. VASCULITIS
• Heterogeneous group of disorders linked by
the primary finding of inflammation within
blood vessel walls.
• Can be primary or secondary
• Constitutional symptoms: fever, weight loss,
malaise, arthralgias/arthritis (common to
vasculitides of all vessel sizes)

34. Takayasu Arteritis
• The pulseless disease or occlusive
thromboaortopathy
• Most frequently in young women.
• Most commonly in Japan, China, India, and
Southeast Asia.
• Arterial stenoses 3-4 times more often than
aneurysms. Claudication (upper [60 %] versus
lower extremities [30 %]) is the most common
complaint and bruits (approximately 80 percent),
blood pressure, and pulse asymmetries (60-80 %)
are the most common findings.

35. • Aneurysms are most common and clinically most
significant in the aortic root, where they can lead
to valvular regurgitation (approximately 20
percent)
• Hypertension is most often caused by renal artery
stenosis, but can also be associated with
suprarenal aortic stenosis or a chronically
damaged, rigid aorta.
• Cardiac, renal, and central nervous system (CNS)
vascular diseases are the principal causes of
severe morbidity and mortality.
• Coronary artery vasculitis is rare(< 5 %)

36. Treatment
• Corticosteroids are the mainstay of treatment of active
TA.
• Initial dose of prednisone1mg/kg is continued for 4 to
12 weeks before commencing a gradual taper.
• Frequently requires revascularization procedures
• Surgical intervention should be deferred until TA is in
remission
• Bypass surgery yields better results than angioplasty.
With bypass graft procedures, autologous vessels give
better results than synthetic grafts

37. Giant Cell Arteritis
• Cause of GCA remains unknown, the
inflammatory lesion begins in the adventitia.
• Most characteristic features of GCA are new
onset of atypical and often severe headaches,
scalp and temporal artery tenderness, acute
visual loss, polymyalgia rheumatica, and pain in
the muscles of mastication.
• GCA may produce clinically apparent aortitis in
~15 % of cases and involve the primary branches
of the aorta, especially the subclavian arteries,

38. Treatment
• Prednisone (0.7 to 1 mg/kg/day) will reduce
symptoms within 1 to 2 days and often
eliminate symptoms within 1 week. About 2 to
4 weeks after clinical and laboratory para-
meters, tapering of CS can begin.

39. Churg-Strauss Syndrome
• Rare syndrome that includes a history of asthma,
eosinophilia, pulmonary infiltrates, upper airway
inflammation, and a variable frequency of renal,
neurological, cutaneous, and cardiac
involvement.
• Cardiac disease in CSS is the most common cause
of death. It is reported in 15 to 55 percent of
cases and may include pericarditis, myocarditis,
and coronary arteritis. Congestive heart failure
occurs in 15 to 30 percent of cases.

40. • Corticosteroids are mainstay.
Cyclophosphamide is another option.

41. Polyarteritis Nodosa
• Nongranulomatous disease of only medium-
sized arteries.
• Necrotizing changes seen, with weakening of
the vessel wall and aneurysm formation or
myointimal proliferation, causing stenosis and
occlusion.

42. • Features include
– painful nodules (similar to erythema nodosum) or
– infarction and gangrene (30 to 50 percent),
– neuropathy (especially mononeuritis multiplex, 20
to 50 percent),
– renal infarction and insufficiency (approximately
10 to 30 percent),
– hypertension (approximately 30 percent),
– segmental pulmonary infarctions (less than 40
percent), and
– cardiac disease (10 to 30 percent; congestive
failure, angina, infarction, pericarditis).
• PAN like spectrum obligates a search for bacterial and fungal infections as
causes of endocarditis or endovascular vegetations.

43. Kawasaki Disease
• Acute febrile systemic illness of childhood.
• Features – fever, conjunctivitis, adenopathy, rash,
mucocutaneous changes & others
• Cardiac abnormalities - pericardial effusions (~ 30
%), myocarditis, mitral regurgitation (~ 30 %),
aortitis and aortic regurgitation (infrequent),
congestive heart failure, and atrial and ventricular
arrhythmias.
• Deaths usually result from acute coronary artery
thrombosis in aneurysms that form following
vasculitis.

44. Treatment
• High dosages of aspirin and IVIG
• Aspirin - 80 to 100 mg/kg/day until the patient
is afebrile After fever subsides, the dose of
aspirin is reduced (3 to 5 mg/kg/day) to
achieve primarily antiplatelet effects.
• Lifelong aspirin if aneurysms persist

45. a
Diseasea Pericardium Myocardium Endocardium
(Valves)
Coronary
Arteries
Peripheral
Vessels
SLE ++ + ++ + +
Systemic
Sclerosis
+ ++ 0 ++ +
PAN +/- + 0 ++ +
Ankylosing
Spondylitis
0 +/- ++ 0 0
RA ++ + + + 0
Polymyositis/
dermatomyosi
tis
++ ++ +/- +/- 0
Takayasu
Arteritis
0 0 + + ++
APLA 0 0 + + ++
CSS + + 0 + +/-
GCA 0 0 0 0 ++
Kawasaki d/s + + +/- +/- 0

46. THYROID

57. DIABETES
• CAD is the most common cause of death in adults
with diabetes mellitus.
• Diabetes mellitus, both insulin- and non-insulin
dependent, is an independent risk factor for
coronary artery disease and accounts for 14–50%
of new cases of cardiovascular disease.
• Pathogenesis- involves endothelial dysfunction,
increased lipoprotein peroxidation, increased
inflammation, a prothrombotic state, and
associated metabolic abnormalities.

59. .Diabetic patients are more likely to have a
myocardial infarction, have a greater burden of
CAD, have larger infarct size, and have more post
infarct complications, including heart failure,
shock, and death.
.“silent ischemia,” resulting from autonomic
nervous system dysfunction, is more common in
diabetic patients, accounting for up to 90% of
their ischemic episodes.

60. • Patients with diabetes mellitus also may have
abnormal left ventricular systolic and diastolic
function, reflecting concomitant epicardial
CAD and/or hypertension, coronary
microvascular disease, endothelial
dysfunction, ventricular hypertrophy, and
autonomic dysfunction.

61. • The increase in intramyocardial lipid
deposition that is characteristic of diabetic
states may contribute to both systolic and
diastolic dysfunction by impairing insulin
signaling, reducing trans-sarcolemma calcium
flux, and inducing myocyte apoptosis.
• Restrictive cardiomyopathy may be present
with abnormal myocardial relaxation and
elevated ventricular filling pressures.

63. ALCOHOLIC CARDIOMYOPATHY