AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Kenya Cardiac Society July 2023 22 The precise epidemiology of CA is uncertain owing to the rarity of cardiac involvement of amyloidosis [4]. However, studies indicate that this may be attributed to significant underdiagnosis [2, 6, 11]. Therefore, increased awareness, clinical suspicion, and improved non-invasive diagnostic capabilities are expected to change this in the future [3]. This article aims at presenting three case reviews of patients suspected to have cardiac amyloidosis and, subsequently, underwent non-invasive diagnostic evaluations for the same. Case One Mr T.W.G. an 80-year-old patient living with hypertension on medication presented to the clinic with uncontrolled blood pressure. However, he had poor drug compliance and poor followup. Initial electrocardiogram (ECG) and echocardiogram (Echo) findings revealed moderate concentric LVH with grade II diastolic dysfunction and a mildly dilated LA. Simpson’s LVEF was 54.9%. All the aforementioned were in keeping with hypertensive heart disease. His antihypertensive medications were reviewed and changed to target optimal BP control (<130/80 mmHg) [10]. He was also advised on the need to adhere to his drug regimen, do regular follow-ups, and do home BP charting. Notably, 6 months later, Mr. T presented with limiting exertional dyspnea, bilateral lower limb swelling, and dry cough. Significant findings in a repeat echocardiogram included deteriorating LVEF (43.7%) with moderate LVH, grade III diastolic dysfunction, and global hypokinesis of the LV ventricle. Due to the reduced LVEF, Mr. T was started on anti-failure medication with the plan for a coronary angiogram to rule out coronary artery disease (CAD) as a contributor to the low LVEF. A year later, Mr. T progressively worsened into NYHA class IV exertional dyspnea. He had troublesome bilateral upper limb peripheral neuropathies limiting his ability to perform several tasks despite being on medication. Further evaluation revealed that he was having bilateral carpal tunnel syndrome with median nerve neuropathy and was planned for median nerve release. An Echo done during this period showed that the LVEF had worsened to 2530%, global hypokinesis of the LV ventricle, grade IV (restrictive) diastolic dysfunction, and severe asymmetric LV hypertrophy. His NTproBNP was elevated at 1297 pg/ml. This prompted us to think of an infiltrative cardiomyopathy. Hereby, he was sent for a cardiac magnetic resonance imaging (CMR) and the results confirmed that there were features suggestive of an infiltrative cardiomyopathy, likely cardiac amyloidosis. Other findings included a reduced LV systolic function (36%), and mild tricuspid and mitral regurgitation with moderate bi-atrial enlargement. To follow it up, Mr. T was sent for nuclear medicine bone scans and the cardiac tracer uptake was suggestive of ATTR cardiac amyloidosis. In addition, free light chains were done around the same period revealing high S-Kappa Free Light Chains with a high Kappa/Lambda ratio. Case Two Mrs. B.W.G. a 73-year-old female referred for a cardiologist’s review after presenting with bilateral lower limb swelling, irregular heart sounds, and cardiomegaly on a chest radiograph. A cardiac evaluation using an ECG/Echo revealed sinus arrhthymia, moderate asymmetric LVH, RVH, with preserved LV systolic function (LVEF was 56%). Additionally, she had mild bi-atrial enlargement and mild tricuspid regurgitation with elevated pulmonary pressures. The transmitral spectral Doppler flow pattern was suggestive of impaired LV relaxation. She was, subsequently, sent for a CMR whose summary findings included cardiomegaly with bi-atrial enlargement and diffuse LVH/ RVH. Notably, the papillary muscles and inter-atrial and interventricular septa were all diffusely hypertrophied. The LV systolic function was severely reduced with an ejection fraction of 37%. There was also altered blood pool kinetics with a reverse nulling pattern. Moreover, she was noted to have diffuse transmural left and right ventricle late gadolinium enhancement (LGE). A serum profile electrophoresis with free light chains showed an elevated S-Kappa free light chain with a high normal Kappa/ Lambda ratio. She was, however, unable to go for nuclear bone imaging owing to financial constraints. Case Three Mr. S.K.G. an 80-year-old male noted to have asymmetric LVH on a baseline ECG/Echo. Consequently, he was sent for CMR and the findings included cardiomegaly with severe RA dilatation, asymmetric LVH, wall motion abnormalities in LV (hypokinesia of IV septum: basal and mid-cavity). Furthermore, he had a reduced LVEF at 46%, moderate TR, mild MR, and mild pericardial effusion Here, further evaluation for possible cardiac amyloidosis was abandoned as the CMR was not convincing for an infiltrative cardiomyopathy. This is because there was no left or right ventricle LGE, no bi-atrial enlargement, no atrial septal thickening, no left ventricular outflow tract obstruction with no associated systolic anterior motion of the mitral valve. Furthermore, he was having a normal mitral valve E/A ratio not indicative of diastolic dysfunction unlike in patients with infiltrative cardiomyopathy [1, 11, 13]. Discussion The sequence of events illustrated in the initial two cases establishes a diagnostic pathway and key findings in CA. This is evidenced by: i. Clinical presentation: Both patients are over 70 years with hypertension and symptoms of clinical heart failure. Such symptoms include progressive dyspnea, lower limb swelling, and dry nocturnal cough [1]. Additionally, bilateral upper limb peripheral neuropathies may be indicative of systemic involvement [3, 7]. This is because carpal tunnel syndrome has been shown to be one of the early diagnosis associated with ATTR CA [7]. ii. Echocardiography Findings: The echocardiography findings are suggestive of infiltrative cardiomyopathy rather than hypertensive heart disease. These include worsening systolic and diastolic dysfunction despite adequate management of heart failure alongside well-controlled BPs [11]. Also, the asymmetric LVH with a speckled myocardium raised suspicions of infiltrative cardiomyopathy further [1, 13]. Notably, patients with CA have also demonstrated regional wall motion abnormalities with reduced longitudinal strain and this is evidenced by the noted global hypokinesis [1]. iii. Cardiac Magnetic Resonance Imaging (CMR) CMR is increasingly being used as a critical noninvasive diagnostic measure in diagnosing CA [3, 14]. The CMR findings were consistent with infiltrative cardiomyopathy. Firstly, there was diffuse transmural left and right ventricle late gadolinium enhancement (LGE) which is considered a classical finding in CA [1, 12]. Also, some of these patients exhibited altered blood pool kinetics with a reverse nulling pattern which has been considered one of the accurate non-invasive methods of detecting CA [8]. Moreover, other findings such as hypertrophied left and right ventricles, valvular regurgitation, and bi-atrial enlargement can also be seen in CA [4, 14]. CMR also helps distinguish hypertensive from infiltrative cardiomyopathy [1, 14]. iv. Nuclear bone scans The cardiac tracer uptake on the nuclear bone scans done was suggestive of ATTR CA. Notably, this indicates the presence of transthyretin amyloid deposits in the heart [12]. Radionuclide imaging has been shown to help distinguish between ATTR and AL amyloidosis and thus an integral part of the CA diagnostic chain [1]. v. Natriuretic biomarkers and serum protein electrophoresis NT-proBNP is a biomarker associated with heart failure; elevated levels can indicate cardiac stress [2]. The noted elevated NTproBNP level further supports the presence of significant cardiac dysfunction. Notably, this marker has also proved imperative in monitoring the prognosis of CA patients [1, 17]. Lastly, elevated S-kappa free light chains with an increased Kappa/ Lambda ratio are indicative of monoclonal gammopathy [16]. The combination of elevated free light chains and evidence of cardiac involvement supports the diagnosis of systemic amyloidosis. Importantly, the sFLC assay can also be applied as a prognosticating factor during the follow-up of these patients [6, 17]. All the aforementioned supports a diagnosis of CA, specifically ATTR CA. This diagnosis has been commonly misdiagnosed as hypertensive cardiomyopathy and, thus, underestimating its true prevalence [1]. This would, consequently, warrant the prescription of Tafamidis, which is an FDA-approved agent shown to increase
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