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Cardiovascular Changes in Sickle Cell Anaemia
*R.A. ADEBAYO fwacp, * M.O. BALOGUN fmcp, § N.O. AKINOLA fmcp, FMCPath, *A.O.AKINTOMIDE fwacp. Departments of "Medicine, Haematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospital Complex, He-He, Nigeria
Nigerian Journal of Medicine, Vol. II, Mo. 4, October-December, 2002
the commonest inherited
haemoglobinopathy in Nigeria anil is associated with liigh
morbidity and mortality, particu/ar/v in early childhood in
most oj'the affected population. The cardiac
manifestations of SCA are a significant feature of the disease
but there is a paucity of information on the cardiovascular
involvement in SCA in Nigeria and Africa. The size of the
sickle cell problem in the country ix growing rapidly and there
should therefore be a greater awareness of the cardiac
problems associated witli SCA. This review highlights
the clinical features, changes in cardiac structure and function
at rest and on exercise, cardiac pathology and associated
heart diseases in SCA as well as the recent global progress
made in the understanding of the cardiovascular changes in
the disease, Emphasis is laid on data derived from Nigerian studies.
KEYWORDS: Sickle cell anaemia; Cardiovascular; Haemoglobinopathy.
Sickle cell anaemia (SCA) is the commonest symptomatic haemoglobinopathy in Nigeria with a prevalence of 2% and the most troublesome in terms of frequency and severity of clinical manifestations1'2.
The heart is largely involved and cardiac signs and symptoms were prominent in many of the early cases of SCA described . SCA has been thought to be associated with cardiomyopathy and cardiac dysfunction5"10. However, echocardiographic studies of ejection phase indices have reported conflicting data in patients with SCA living in America12"16 and in Africa13"16. In addition, conflicting reports have been observed with respect to its association with mitral valve prolapse17"20.
Despite the high prevalence of the disease in Nigeria, there is paucity of data on the cardiovascular involvement in SCA in the country and Africa as a whole, as most of the previous works and reviews were from North-America. Therefore, this article reviews the literatures on the clinical features, changes in cardiac structure and function at rest and on exercise, cardiac pathology and associated heart diseases in SCA.
Cardiovascular Alteration in Sickle Cell Anaemia and other Chronic Anaemias
Chronic anaemia and SCA have a series of well-described effects on the heart21'22. Cardiac dilatation and hypertrophy are known to be associated with chronic anaemia22'23. The cardiovascular alterations in SCA often vary in type and degree from those found in other causes of anaemia22. The chronicity of the anaemia, the increased viscosity of the red blood cells, the microthrombi and tissue infarctions, the characteristic oxygen undersaturation of arterial blood and the more pronounced rightward shift of the oxyhaemoglobin dissociation curve probably influence the response of the cardiovascular system in SCA'4
Klinefelter25 produced the first systemic review of the cardiovascular findings in this disorder in an attempt to detect distinguishing features which could be attributed to the chronic anaemic state. He concluded that the cardiac changes seen in SCA were more marked tnan the changes found in other anaemias because- of the long duration of the severe anaemia. The reduced oxygen carrying capacity due to anemia increases demand on the heart with an increase in cardiac output26. This increase is achieved in chronic anaemia predominantly by increased stroke volume2627, which results in the clinical findings of hyperdynamic circulation, heart murmur and cardiomegaly. Cardiomegaly in children with SCA is a healthy adaptation to anaemia and should not by itself be considered pathologic26. The cardiac output is elevated with less severe anaemia in patients with SCA and the auscultatory findings associated with anaemia tend to be present in SCA patients at a higher hemoglobin level than in other anaemic patients22.
Both preload and afterload are altered in SCA28. Cardiac dilatation increases preload and decreased peripheral resistance reduces afterload. In severe anaemia, cardiac output and stroke volume increase because of both cardiac dilatation and decreased peripheral vascular resistance22 2j
When cardiac decompensation occurs in patients with SCA or other forms of chronic anaemia, it is usually the result of other coexisting complications of the SCA or the presence of underlying cardiovascular abnormalities. For instance, deaths secondary to congestive cardiac failure occurring in children and young adults with SCA are usually precipitated by chronic renal failure, pulmonary thrombosis, or infections2329.
Complaints of dyspnoea on exertion, easy fatiguability and palpitations are frequent in SCA4, and these may lead to clinical misdiagnosis of heart failure Seven of the 12 patients studied by Klinefelter had exertional dyspnoea without frank evidence of congestive cardiac failure26.
On examination of the patient, signs of cardiovascular agitation are most typically seen in those with Hb level of less than 7g per 100ml of blood4. These may include prominent pulsations in the neck, often accompanied by a thrill in the suprasternal notch and the base of the right side of the neck. A thrill in the suprasternal notch was noted in 15 patients (41 percent) by Ng et al.30 and was significantly more common in
children with low Hb levels. The jugular venous pressure is rarely raised in the absence of cardiac failure13
There is collapsing pulse with tachycardia as well as visible praecordial and apical impulse that is not easily located, although forceful in character when located . There is a high output state in SCA31, but cyanosis is extremely uncommon4.
Blood pressure in the steady state is lower than normal and fails to show the age-related rise common in normal populations32"36. The mechanism is unclear. Intermittent systolic hypertension has been described during the painful crisis37 but the frequency or mechanism of the finding is unknown. Hypertension with convulsions has occasionally followed blood transfusion38'39.
A left parasternal heave is common and a pulsation may be palpated over the pulmonary artery in the second left intercostal space. An accompanying loud pulmonary component of the second sound suggests a diagnosis of pulmonary hypertension, but pulmonary artery pressures are usually normal in such cases. These signs probably result from a pulmonary artery dilated from carrying high blood flows, palpated more readily because of a thin chest wall5.
On auscultation, the first and second heart sounds are loud and frequently split more widely than normal, consistent with the increased haemodynamic load. A loud third heart sound and mid systolic (ejection type) murmurs are common5. Diastolic flow murmurs, which represent increased flow across normal atrio-ventricular (A-V) valves, are also heard frequently40. Mid-diastolic rumbles were noted in 13/36 (36%) children by Ng et a!30. Patients without audible murmurs tend to be those without cardiomegaly and with high Hb levels5. Cardiac Structure
The changes in cardiac structure are age dependent5. Cardiac enlargement was one of the earliest cardiovascular features of SCA patients3'2641 and was found to occur early in childhood6 with most SCA children developing cardiomegaly in their first 5 years5. In adults, left ventricular hypertrophy (LVH) is almost constant and right ventricular hypertrophy (RVH) is common, depending on the method of detection .
There is often a cardiomegaly with a globular configuration from an early age42. This is a result of the hypovolaemic circulation from the chronic anaemic state. The lungs show multiple interstitial scars which cause a generalised loss of translucency to the lung fields; this together with coarse trabeculation of the widened ribs, gives the characteristic appearance to the chest x-ray of patients with SCA42. Enlargement of the heart was confirmed radiologically in three-quarters of SCA patients4344. The cardiac dilatation is usually moderate, affecting mainly the LV with prominence of aortic knuckle, but in patients with frank mitral regurgitation or additional stress like pregnancy, cardiac enlargement may be gross4. The increased heart size on X-ray reflects not only dilatation, but also cardiac hypertrophy .In a group of SCA children aged 2-17years, Ng et al.30 found cardiomegaly in 86% radiologically and there was radiological evidence of a dilated vessel system, a prominent aortic arch occurring in 47 percent and increased pulmonary markings in 36% of the children
Steven et al. , in their comparison of cardiac si2 using cardiothoracic ratio (CTR) in SCA children ar with matched AA controls, found that heart size wj significantly greater in SS disease before the age 1year and values continued to diverge up to the age of years, but no correlation was found between the degr« of cardiomegaly and Hb level. However, the degree cardiomegaly may be inversely related to the Hb level older children and adults27.
Akinola and Balogun4647, assessed l\ cardiovascular status of 22 adult Nigerians with SCA ar 22 controls and found that SS patients had significant larger hearts than AA controls, the CTR ranged fro 0.46 to 0.63 for SS patients and 0.37 to 0.50 for ft individuals.
The electrocardiographic (ECG) changes are simil to those seen in other chronic anaemias and do n appear to be specific to SCO5 40. Such non-specific EC changes described include prolongation of PR interv; sinus arrhythmia, first degree A-V block, reversible wave inversion in the praecordial leads, flattening of wave and abnormal septal Q-waves25 40'48~50 The ( waves are believed to be secondary to septal thicknes the increased LV mass and degree of anaemia40 5L.
Voltage criteria for ventricular hypertrophy must I applied cautiously, since there is some evidence th higher voltages may occur as a normal racial variation black population and the lack of skin fat and thin che walls in patients with SS disease may contribute to hi< recorded voltages6. Voltage evidence of LVH occurn in 18 per cent of 148 SCA patients reviewed by Uzso> and in 20/34 (59%) children studied by Ng30.
Seven patients (21.2%) of the thirty three adi Nigerians with SCA studied by Adebiyi17 had prolonged QTc while the QTc was within normal limits all the controls. There were significant different between the patients and the controls in the T-waves leads V2 and V3, with 15 patients (48.4%) and 4 centre (12.9%) having low or inverted T-wave in V2, and patients (41.9%) and one control (3.3%) having low inverted T-wave in V3. The ECG of SS patients studn by Odia52 had statistically preponderance of T-wa inversion in more than one right ventricular lead and suggested that the T-wave abnormality in the patier might be an index of right ventricular ishaemia.
Akinola and Balogun4647 found abnormal restii ECG in 16 (72.7%) SS patients. Abnormalities sei included voltage LVH in 14 (63.8%) patients, sin arrhythmia in 6 (27.3%), prolonged PR interval in (9.1%), unifocal premature ventricular contraction (PV in 3 (13.6%), sinus bradycardia in 1 (4.5%) and no specific intra-ventricular conduction defect in 5 (22.7°/ T-wave inversion and non-specific T-wave chang occurred more in SS patients than normal controls, b obvious changes suggestive of ischaemic heart disea were not found.
Thirty-eight (48%) of 78 Nigerian SS children ai adolescents studied by Aluko53 had LVH, 1(1.3%) h; RVH while 14(17.9%) had biventricular hypertrophy. S T changes were found only in 7(9%) of the patients.
Echocardiographic studies of cardiac structure a size in children and adults with SCA confirmed tr
chamber enlargement and myocardial hypertrophy with increased left ventricular mass (LVM) were common15"
Balfour et al6, in their studies of 124 children and adolescents with SCA, noted significant increases in left atrial (LA) and LV diastolic dimensions and LVM, all which increased with age. In comparison with a control group of 28 normal black children, Rees and associates7 found that 35 symptomatic children out of a total 44 with SCA had significantly higher LV end-diastolic dimension (LVEDD) and cardiac index.
In a study of 23 adult SCA patients and 9 normal controls, Gerry and colleagues observed that SCA patients had significantly greater mean LV systolic and diastolic dimension indices, LVM, stroke volume index, interventricular septal width, aortic root index and LA index. Simmon et al.17 noted that abnormalities were found more frequently in the left than the right heart of the adult SCA patients studied, as manifested primarily by increased LVM, and LV and LA dilatation.
Adebiyi et al.16 found that there were significant differences between the Nigerian SCA patients and controls in the estimate of RV, LV, aortic root and LA dimensions, and LVM indexes, with the LV posterior wall thickness in systole being significantly larger in the patients. LV dimensions were also increased in SS patients in the study by Braden and Colleagues58, but they had normal septal and posterior wall thickness.
The recently concluded Cooperative Study of Sickle Cell Disease by Covitz et al.54 showed that stable SCO patients had dilated chambers and septal hypertrophy. In another study on 22 adolescents and young adults with SCA, Covitz and Colleagues12 revealed LVH in all the patients, with resulting high stroke volume and cardiac output. Lewis et al.36 found that LV transverse end-diastolic dimension was greater in 30 SCO patients compared to 30 controls, and that calculated LVM and LV mass index was also increased in the patients than the control.
LV dimension was found to be inversely related to Hb level14'54, and age (duration of illness) was an important factor in that relationship54. However, Kilinc et al. did not find any correlation between echocardiographic findings of the 30 SCA children and their haematological indices, despite the LV volume load and dilatation. Similarly, Covitz et al.12 noted that the dilated ventricles and increased cardiac output did not correlate significantly with haematocrit.
Mitral Valve Prolapse: Lippman et al.18, using M-mode echocardiography diagnosed mitral valve prolapse (MVP) in 25% of 57 patients with SCO. All these patients had a mobile systolic click and/or late systolic murmur. This figure was significantly greater than the reported 5 to 6% prevalence in general adult population and 3% (1/35) in the anaemic control group. The authors postulated that this unexpected high prevalence of MVP in SCO patients is due to an abnormality in collagen or elastic tissue.
However, other workers have presented contrary reports to the above. Simmon and Colleagues17 found that valvular structures were normal in their 40 SCA patients despite an increased incidence of flow murmur. There was no association with myxomatous valvular degeneration or MVP. Hussain et al.20, in a prospective controlled study of 316 subjects divided into four groups of SCO, sickle cell traits, those with other anaemias and
normal control found the prevalence of MVP to be 17.4%, 21.4%, 19.4% and 13.3% respectively. They concluded that the prevalence of MVP by echocardiographic criteria (M-mode and 2-dimensional) in SCO patients was the same as in the general population.
Cardiac Function and Haemodynamics
A. At Rest
i. Heart Rate: Most workers6'9'13'46'51 found higher resting heart rates (HR) in patients with SCA compared with normal controls. Akinola and Balogun47 demonstrated that the mean resting HR of SS patients, although normal, was significantly higher than that of normal controls. Adebiyi13 also founci that the mean resting pulse rates was significantly higher in the patients than the normal controls.
Others workers6'51 also reported a significantly higher resting HR in SCA patients compared to control subjects, and a sinus tachycardia occurred in 27% of one series51. However, Lewis36 and Rees7 found no statistically significant difference between the normal resting HR of SCA patients and the controls.
ii. Blood Pressure: Some studies13'32"36 had shown that the normal blood pressure (BP) in steady state of SS patients is lower than those of controls. Akinola and Balogun47 found that the mean resting systolic BP was normal and not different from AA controls. It also failed to show the expected rise with age. Adebiyi13 demonstrated no significant difference in the systolic and mean arterial BP in the patients and controls. However, the pulse pressure was significantly higher in the patients compared with the controls.
iii. Cardiac Output: Cardiac output (CO) in SCA is constantly elevated at rest, with cardiac index ranging from 3.6 - 11.71/min/m25'9'13'16'28'41'59'60
Lindsay et al.61 noted that the greatest CO tended to occur in patients with the lowest Hb levels. However, Leight et al.31 was unable to demonstrate a relationship between cardiac index and Hb. Some studies had found that the cardiac index and stroke index were significantly elevated in SCA patients while the total peripheral resistance index was significantly reduced in them when compared with controls '41|6°.
iv. Echocardiographic assessment of LV Function
The LV echocardiogram is an effective technique for the noninvasive determination of LV dimensions and function62.
(a) Systolic Function: Many echocardiographic studies of ejection phase indices of LV function in SCA have reached conflicting conclusions5"10'14"
Rees et al.7 observed significant differences in SCA children and the normal group in LV ejection fraction, cardiac index, mean velocity of circumferential fibre shortening (Vcp), and the percentage shortening of LV minor axis. Only symptomatic SCA patients had significantly depressed LV performance indices. In another study on children and adolescents, Balfour and Colleagues6 identified abnormality of systolic time intervals (STI) when the opposing influence of volume
overload due to anaemia and ventricular dysfunction were separated, although contractility indices were normal. LV STI ratio and LV preejection period were higher in the SCA group and became increasingly abnormal with age, suggesting that LV function deteriorated with time.
Denenberg et al.28, in their study of 11 SCA patients and controls, questioned the validity of using ejection phase indices as indication of LV function under the altered loading condition in chronic anaemia. They found increased preload (end-diastolic volume), reduced afterload (reduced systemic vascular resistance), a high cardiac index and normal ejection fraction (EF). They observed that increased preload and decreased afterload compensated for the LV dysfunction and maintained a normal EF and a high CO. The depressed LV muscle contractile performance was demonstrated by the significantly decreased ratio of resting end-systolic stress to end-systolic volume index in SCA patients compared with control subjects. Balfour and associates63 evaluated LV systolic function in 38 SCA patients and 11 normal black subjects. Systolic function, assessed by LV wall stress, was significantly decreased in the patients.
To determine if there are chronic changes in cardiac function, 13 subjects with SS Hb were studied between crisis by Val-Mejias and co-workers56. Those under 23 years of age were not dissimilar from a group of normals and a group of patients with chronic blood loss anaemia. A significant abnormality of the pre ejection period (PEPJ/LV ejection time (LVET) ratio was observed in subjects over 23 years of age. Similar observations were made on echocardiography, with subjects above 23 years demonstrating an abnormal EF compared to the younger group, despite enhanced end-diastolic diameter. Thus, it was suggested that the chronic hemolytic process in subjects with SCA may effect cumulative myocardial alteration, resulting in chronic cardiac malfunction in the apparent absence of acute ischaemia during crisis.
In contrast to the above findings, the following researchers reported an essentially normal LV systolic function in SCA patients9'11'12'14'16-18^'4'55'57'58
Adebiyi et al.16 did not demonstrate any significant difference in the LV systolic function at rest between SCA patients and controls. There were no significant differences in the STI, LV fractional shortening, EF and vcf between the 2 groups. In addition, no significant difference was noted in the end-systolic stress, end-systolic dimension index ratio and in the slope of the relationship between the end-systolic stress and the end-systolic dimension index in the 2 groups. Simmon and Colleagues17 found preserved LV function, as evidenced by normal EF, in their SCA patients.
The conclusion of Gerry et al.11 that LV dysfunctions were uncommon findings in SCA patients and were no more prevalent in older patients than in younger ones was based on their findings of no significant differences in the vcf, EF or STI between patients and normal controls. In addition, there was no decline in LV function in patients over SOyears as compared to younger subjects, suggesting that cardiac involvement in this disease was not progressive. Covitz et al.54 found normal LV contractility in stable SCA patients with normal STI ratio and fractional shoitening (FS), though LVET was prolonged and vcf was abnormally low. They
concluded that no specific cardiomyopathy was associated with SCA. Kilinc et al.55 demonstrated normal LV systolic function in SCA patients, as LV fractional shortening (LVFS) was more or less the same with controls. Braden and coworkers58 found that Doppler indices of systolic function were not significantly different between SCA groups and normal values.
After their assessment of cardiovascular features in 55 adolescents and adults SCA patients in Kenya, Ayuo and associates14 found that 80-90% of patients had normal LV systolic function. Covitz et al12 also demonstrated normal LV systolic function at rest in SCA patients, as shown by normal EF. Lippman and colleagues18 did not show abnormal LV systolic function in their 57 SCO patients, as indicated by normal percent FS, systolic wall thickening, and endocardial motion to suggest papillary muscle dysfunction. Covarrubias et al. also concluded that cardiac function at rest was normal in patients with SCA, after studying 14 patients using simultaneous echocardiography and phonocardiography. They found that STI and echocardiographic indices of LV function were similar to those of normal subjects and those with comparable degree of anaemia.
(b) Diastolic Function: The exact contribution of diastolic dysfunction to morbidity and mortality in many disease states and its relationship to systolic dysfunction remains to be defined64, Digitized M-mode echocardiography and 2 Dimensional echocardiography have been used to measure LV filling64. Doppler echocardiography, using the pulsed wave Doppler is being increasingly used to detect LV diastolic abnormalities since it may provide an accurate non-invasive beat-to-beat evaluation of LV diastolic function64"68.
Simmon et al.17 suggested that the effects of SCA on the cardiovascular mechanism may be consequent on diastolic dysfunction secondary to long term volume overload. This was after they found no systolic abnormality in their SCA patients using echocardiography. Adebiyi et al.16 also demonstrated normal systolic function at rest in SCA patients and suggested that the prominent cardiovascular abnormalities seen in these patients might have resulted from LV diastolic dysfunction.
Lewis and coworkers36 clearly demonstrated that LV filling abnormalities were evident with Doppler echocardiography in many patients with SCA, even in the absence of symptoms of heart failure or LV systolic dysfunction. Seventeen (57%) of the 30 patients had evidence of abnormal diastolic filling while the remaining 13 patients showed normal filling pattern. Six of these 17 patients had a 'restrictive' filling abnormality while the remaining 11 showed impaired LV relaxation pattern.
In another study by Braden et al.58 cardiac functions at rest and during exercise were measured in 9 patients with SCA and coexisting homozygous alpha thalassemia-2 (alpha thal-2) and the results were compared with 18 matched SCA patients with normal alpha globin gene and published normal values. SS alpha thal-2 patients did have abnormal diastolic filling at rest, as evidenced by a reduced ratio of early/late diastolic filling, even after correcting for LVH. The recent results of Doppler assessment of LV diastolic function of 41 SCA patients and merged controls suggested that LV
filling abnormalities were present in patients with SCA despite their normal systolic function9' °.
B. Cardiac Function on Exercise
There is much evidence that the response to exercise is abnormal in SS disease6'9'26'46. On mild exercise, the heart rate (HR) increases by a similar proportion as that observed in AA controls but much greater increases are apparent in cardiac index and stroke volume60.
On maximal exercise, heart ratos (HRs) were lower than in healthy black controls9'46. In addition, duration of exercise, pressure rate product, change in resting to maximal HRs and 5-minutes post exercise HRs were significantly lower in SCA than normal controls46'47.
The CO triples on maximal exercise in normal adults but the average increment was only twice the resting level in SS disease12. Since the CO determines the work capacity, this is also reduced. The work capacity was found to correlate with the haematocrit and to fall in serial observations in adolescents over 5-6years12.
Exercise performance improved markedly following isovolaemic partial exchange transfusion with normal blood69 and also following simple transfusion70'71. The role of myocardial ischaemia in limiting the work capacity of SS patients is unclear5. ECG chjinges interpreted as ischaemic occurred on exercise in 7/47 (15%) children aged 5-18years72. Such patients achieved lower maximal HRs and work capacities on exercise, and also had lower Hb levels. These observations were noted by Covitz et al.12 who explained that in patients with ECG evidence of ischaemia, the ejection fraction (EF) actually fell on maximal exercise compared lo an increase in SS patients without ECG changes of ischaemia.
This study by Covitz and colleagues12 on exercise induced cardiac dysfunction in 2'.' adolescents and young adults with SCA also revealed a decrease in LV end-diastolic volume with exercise. The authors suggested that an abnormality of ventricular filling (diastolic function) was present and might be a factor contributing to the poor exercise performance of these patients. Similarly, Balfour et al.6 showed evidence of diastolic dysfunction consisting of reduced rate of change in LV cavity diastolic dimension and posterior wall thinning in SCA patients compared with normal controls. They suggested that in some of these patients' abnormalities of diastolic function might be responsible for exercise intolerance and failure of LV EF to increase appropriately during exercise.
Cardiac Pathology and Myocardial
Sickle cell Anaemia
Typically, there is cardiomegaly with LVH and RVH. The heart valves and pericardium are usually normal5.
Clinical and autopsy studies in adult SS patients demonstrated the infrequent occurrence of myocardial infarction (Ml) in them. Coronary anatomy in these patients is remarkable for the absence of significant atherosclerosis. SCA is normally associated with dilated coronary arteries free of atherosclerotic plaque28.
Gerry et al.23 studied 52 autopsy patients with SCA and noted no evidence of recent or temote Ml, coronary thrombosis or arteritis in any of them. Renal failure and infection were the most common causes of death, with 17 patients having clinical evidence of congestive cardiac failure before death. Baroldi73 noted intramural
fibrosis in only 8 of his 53 autopsied SCA patients, the pathological basis of which was unclear. No evidence of coagulation necrosis was found in any of the autopsied specimen and he concluded that Ml due to sickled erythrocytes thrombosis was uncommon.
Pathological confirmation of Ml in SS disease is even less frequent6. Karayalcin et al.74 reported one patient with evidence of Ml but without atherosclerosis and only diffuse intravascular sickling in the coronary arteries. Barret et al.75 described 2 deaths in SS disease from acute Ml with their autopsy revealing minimal coronary atherosclerosis.
D. Sickle Cell Anaemia and Associated Heart Diseases
i. Ischaemic Heart Disease: This is excessively rare in SCA perhaps because few patients demonstrate the risk factors commonly observed in the general population. Obesity is uncommon, serum cholesterol level is low, atheroma is uncommon, BP may be lower than in age-matched controls and until recently, a relatively small proportion of the total SS population reached the aae at which Ml is common in the general population .
Angina may occur in anaemia. Angina is rare in SCA patients. Typical angina and exercise -induced ECG changes were described in a 7 year old boy and were relieved by a transfusion programme76.
ii. Rheumatic Heart Disease: Its frequency of occurrence is unknown5. There is nothing to prevent rheumatic heart disease (RHD) in SCA but it is very rare4. Wiernick77 said there was less than 10 historically documented cases in English literature. True RHD does occur. Multiple valvular involvement has been confirmed by cardiac catheterization31 and at autopsy78.
The clinical features of SCD such as intermittent fever, joint pains, cardiomegaly and heart murmurs may mimick acute rheumatic fever with cardiac involvement and this leads to diagnostic difficulties79. Meanwhile , it is essential that patients with atypical cardiac features be investigated for associated RHD since surgery may offer striking benefits in such patients80'81.
iii. Congenital Heart Disease: Diagnostic confusion
can occur with congenital heart disease (CHD)
which may be erroneously diagnosed in young
children with SCD42'48, but may also be
Harris et al.82 reported 3 cases of CHD among a group of 70 children with SCA. The lesions includes an atrial septal defect and 2 cases of congenital pulmonary stenosis. Transposition of great vessels had also been reported83.
iv. Pulmonary Heart Disease: Pulmonary hypertension secondary to recurrent pulmonary thrombosis with sickled erythrocytes has long been suspected as a complication of SCA84. However, increased pulmonary artery pressure has been a rare finding in studies employing cardiac catheterization31'41.
Simmon et al.17 found that pulmonary hypertension, which was present in 2/3 of their 40 SCA patients, was minimal to moderate as assessed by passive Doppler technique. They
concluded that passive elevation of pulmonary pressure was one of the cardiac effects of SCA.
Death from right heart failure has been described in patients, who ataulopsy, demonstrated multiple thrombotic occlusion of the small and medium sized pulmonary arteries and marked RVH11'85 The time required for pulmonary vascular obstruction to develop appeared to explain why this syndrome was uncommon helow the age of 20years5, although one case or severe pulmonary hypertension was reported in a i;hild of 5 years86. v. Sickle Cell Cardiomyopathy: Congestive cardiac failure is common in SCA over the age of SOyears5'87 and occasionally in younger patients88.
Recognizable causes of caidiac failure such as systemic or pulmonary hypei tension, ischaemic heart disease and valvular disease are rare. After excluding all these potential causes, there remains a group of patients with unexplained congestive cardiac failure.
These observations have led to the hypothesis that a sickle cell cardiomyopathy may result from occlusion or slugging within the small cardiac vessels. Although widely proposed, the evidence supporting this concept is entiiely circumstantial5. Fleischer and Rubier8 described a cardiomyopathy in 6 alcoholic patients with sickle cell traits and suggested that this association was not fortuitous.
However, Gerry et al.23, in i:heir autopsy study, concluded that cardiac dysfunction in SCA can usually be explained by the adverse effect of coexisting disease on the iliminished cardiac reserve of chronic anaemia, and that their data did not support this concept of a specific "sickle cell cardiomyopathy".
Covitz et al.54 also concluded that no specific cardiomyopathy was associated with SCO.
These conclusions may nend to be reevaluated in the light of the echocaidiographic studies indicating functional impairment in the presence of ECG evidence of ischaemia12'7 . The presence of unexplained impaired LV function in some patients with mechanisms for vaso-ooclusion, which is unlikely to spare the myocardium, might be considered strong circumstantial evidence of sickle cell cardiomyopathy5.
The cardiac manifestations of SCA are a significant feature of the disease.
Although, the size of the SCA problem is growing rapidly in Nigeria, the cardiac diagnostic facilities are improving and becoming more available. There should therefore be a greater awareness of i:he cardiac problem associated with SCA.
This review has therefore provided a global glimpse of the recent progress made in the understanding of the cardiovascular findings in SCA with emphasis on relevant Nigerian studies to provide local experience.
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Correspondence to: Dr. R.A. Adebayo
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