CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 2, May/June 2023 124 AFRICA common due to low stroke volume and peripheral tone. Peripheral neuropathy and carpal tunnel syndrome are uncommon in other forms of HFpEF but are seen in many patients with CA. A history of carpal tunnel syndrome is seen in almost half of the patients and this should be considered a red flag for ATTR V122I CA among older patients of African ancestry with HF.29 From a diagnostic perspective, an electrocardiogram may show low voltage in the limb leads or pseudo-infarction pattern. However, 44.3% of patients with ATTR V122I CA have normal or increased voltage and an abnormal electrocardiogram may not be reliable for the diagnosis of ATTR V122I CA cases.30 Echocardiography typically reveals thickened walls, which may be interpreted as demonstrating hypertrophy, either related to hypertension or HCM, both common conditions in African patients. The three most important studies for a patient with suspected CA (with HFpEF and any degree of wall thickening on echocardiogram) are (1) serum-free light-chain assay (kappa and lambda light chains to assess monoclonality as determined by an abnormal ratio), (2) serum and immuno-fixation to assess for the presence of a monoclonal protein, and (3) technetium pyrophosphate scan for myocardial uptake of ATTR. Abnormal monoclonal protein and consistent echocardiographic features are highly suspicious for AL amyloidosis. An abnormal free light-chain kappa/lambda ratio is found in > 90% of patients with untreated AL amyloidosis. All patients with suspected AL amyloidosis should have a bone marrow biopsy to determine the percentage of plasma cells and rule out co-existing multiple myeloma. Biomarker values of NT-proBNP, troponin T, and free light chains have prognostic value in AL amyloidosis. The presence of a positive pyrophosphate scan is highly sensitive for the diagnosis of ATTR CA.31 In the absence of a monoclonal protein, a scan that is graded 2 or 3 in uptake is considered diagnostic of ATTR CA without biopsy.32 However, the presence of a monoclonal protein and a positive technetium pyrophosphate scan makes a tissue biopsy necessary to establish a diagnosis. Many patients with ATTR CA have a detectable abnormality of immunoglobulins. All patients with suspected ATTR CA based on a pyrophosphate scan should have genetic testing and counselling offered for abnormal results. Diagnosis of CA requires a high degree of clinical suspicion due to its ability to mimic other cardiac diseases such as hypertensive heart disease and that there is no single confirmatory diagnostic test. Therapy for AL amyloidosis includes steroids (dexamethasone), proteasome inhibitors (bortezomib) and/ or chemotherapy (cyclophosphamide).34 Tafamidis is an oral stabiliser administered once daily that was tested in wild-type and mutant ATTR CA in the ATTR-ACT trial. This trial demonstrated lower all-cause mortality and cardiovascularrelated hospitalisations with tafamidis compared to placebo, leading to its approval. It has a very favourable toxicity profile. Gene-silencing medications are either small interfering RNAs or antisense oligonucleotides: patisiran and inotersen. They demonstrated improvement in neurological impairment and quality of life when compared with a 15- to 18-month placebo arm in phase 3 trials in mutant TTR peripheral neuropathy,35,36 and are currently being tested in amyloid cardiomyopathy. Supportive management of ATTR CA includes reduction of preload with loop diuretics; either high-dose furosemide > 80 mg daily or torsemide due to superior absorption ± metolazone (can cause hypokalaemia or hypotension). Patients with advanced ATTR CA require higher intravascular fluid volumes and have higher filling pressures and may tolerate diuretics poorly. Tachycardia is compensatory and required to maintain cardiac output. Beta-blockade to reduce the heart rate may result in worsening of symptoms. For patients with supraventricular tachyarrhythmias, digoxin is preferred to metoprolol or carvedilol. Atrial arrhythmias occur commonly in ATTR CA, and cardioversion may be attempted although its efficacy is limited in this patient population. Pacemaker implantation can be beneficial in patients with significant bradycardia, but the value of implantable cardiac defibrillators remains controversial as many patients die with electrical mechanical dissociation, and the efficacy of the defibrillator impulse capture in an amyloid-involved ventricle is uncertain. Orthostatic hypotension is common in patients with amyloidosis and may be due to progression of the disease with moderate/severe cardiac involvement, autonomic failure, or aggressive diuretic therapy. Pulmonary hypertension The conference acknowledged that causes of PH may be different in SSA than in other parts of the world. In SSA, PH may be more commonly due to untreated congenital heart diseases or HIV (WHO group I PH) or group II related to RHD, mitral valve disease or cardiomyopathies or other WHO groups such as PH secondary to schistosomiasis or sickle cell disease.37 PH is classified into five WHO class groups based on aetiology. A distinction needs to be made between pulmonary arterial hypertension (PAH) defined by mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance (PVR) > 2 wood units and pulmonary hypertension secondary to left heart disease.38 PAH is a rare orphan disease and affects approximately two to 3% of patients with PH. However, PH secondary to left heart disease (WHO group II PH), defined as mPAP > 20 mmHg, PAWP > 15 mmHg and PVR < 2 wood units but with PVR > 3 wood units for combined pre- and post-capillary PH, is commoner.38,39 The pathophysiology of PAH involves pulmonary vascular proliferation mediated by the endothelin, nitric oxide and prostacyclin pathway but that of WHO group II PH is due to passive venous congestion. Echocardiogram and right heart catheterisation are important diagnostic tools for diagnosis. In SSA, Dopplerderived echocardiogram measurement of mPAP remains the main method for PH diagnosis although there are some data that Doppler-derived pressures correlate poorly with invasive PA pressures and may be unreliable for making a diagnosis of PH.40 Echocardiogram features such as right ventricular (RV) or right atrial (RA) enlargement, septal straightening, loss of inferior vena cava, respiratory collapse, tricuspid regurgitation and signs of RV systolic dysfunction are shown. Right heart catheterisation is required for confirmatory diagnosis for almost all patients with suspected PH. It measures PAWP or left ventricular end-diastolic pressure (LVEDP), confirms the diagnosis, establishes severity and prognosis, and can be used to monitor progress and test for vasodilatory response for patients with PAH. A vasodilator responder meets the three haemodynamic criteria on right heart catheterisation
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