Jason Dungu

Senile Systemic Amyloidosis: Clinical Features at Presentation and Outcome

Background Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac‐isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors. Methods and Results All patients with biopsy‐proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N‐terminal pro‐B‐type natriuretic peptide (NT pro‐BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro‐BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro‐BNP <1420 pmol/L. Conclusions Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro‐BNP level can aid in distinguishing ATTRwt from AL amyloidosis.

Systemic Amyloidosis in England: an epidemiological study

Epidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60–79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population.

Cardiac transthyretin amyloidosis

Cardiac amyloidosis of transthyretin fibril protein (ATTR) type is an infiltrative cardiomyopathy characterised by ventricular wall thickening and diastolic heart failure. Increased access to cardiovascular magnetic resonance imaging has led to a marked increase in referrals to our centre of Caucasian patients with wild-type ATTR (senile systemic) amyloidosis and Afro-Caribbean patients with the hereditary ATTR V122I type. Both subtypes present predominantly as isolated cardiomyopathy. The differential diagnosis includes cardiac amyloid light-chain (AL) amyloidosis, which has a poorer prognosis and can be amenable to chemotherapy. We review here the clinical features of cardiac ATTR amyloidosis and describe the diagnostic tests to determine ATTR type. Correct diagnosis is ever more crucial given that several novel therapies for ATTR amyloidosis are on the near horizon.

Afro-Caribbean Heart Failure in the United Kingdom: Cause, Outcomes, and ATTR V122I Cardiac Amyloidosis.

Background— It has been reported that subjects of African descent present with heart failure at a younger age and because of different causes than whites. We present contemporary data from UK Afro-Caribbean patients in London. Methods and Results— All patients with heart failure presenting to St George’s Hospital Heart Failure clinic between 2005 and 2012 were included (n=1392). Patients were predominantly white (71%) and male (67%), and median age at presentation was 73 years (range, 18–100 years). In 211 Afro-Caribbean patients, the most common cause of heart failure was nonischemic dilated cardiomyopathy in 27.5% (whites, 19.9%; P <0.001). Lower rates of ischemic cardiomyopathy were observed (13% versus 41%; P <0.001). The fourth most common cause of heart failure in Afro-Caribbeans was cardiac amyloidosis (11.4%). The prevalence may have been even higher as not all patients were tested for amyloidosis. Patients with ATTR V122I had the worst prognosis compared with other causes of Afro-Caribbean heart failure and white patients. To better understand this condition, we analyzed data from the largest international cohort of ATTR V122I patients, followed up at the UK National Amyloidosis Center (n=72). Patients presented with cardiac failure (median age, 75 [range, 59–90] years). Median survival was 2.6 years from diagnosis. Conclusions— In London, the cause of heart failure varies depending on ethnicity and affects age of presentation and outcomes. In Afro-Caribbean patients, ATTR V122I is an underappreciated cause of heart failure, and cardiomyopathy is often misattributed to hypertension. As promising TTR therapies are in development, increased awareness and proactive detection are needed.Background—It has been reported that subjects of African descent present with heart failure at a younger age and because of different causes than whites. We present contemporary data from UK Afro-Caribbean patients in London. Methods and Results—All patients with heart failure presenting to St George’s Hospital Heart Failure clinic between 2005 and 2012 were included (n=1392). Patients were predominantly white (71%) and male (67%), and median age at presentation was 73 years (range, 18–100 years). In 211 Afro-Caribbean patients, the most common cause of heart failure was nonischemic dilated cardiomyopathy in 27.5% (whites, 19.9%; P<0.001). Lower rates of ischemic cardiomyopathy were observed (13% versus 41%; P<0.001). The fourth most common cause of heart failure in Afro-Caribbeans was cardiac amyloidosis (11.4%). The prevalence may have been even higher as not all patients were tested for amyloidosis. Patients with ATTR V122I had the worst prognosis compared with other causes of Afro-Caribbean heart failure and white patients. To better understand this condition, we analyzed data from the largest international cohort of ATTR V122I patients, followed up at the UK National Amyloidosis Center (n=72). Patients presented with cardiac failure (median age, 75 [range, 59–90] years). Median survival was 2.6 years from diagnosis. Conclusions—In London, the cause of heart failure varies depending on ethnicity and affects age of presentation and outcomes. In Afro-Caribbean patients, ATTR V122I is an underappreciated cause of heart failure, and cardiomyopathy is often misattributed to hypertension. As promising TTR therapies are in development, increased awareness and proactive detection are needed.

Patterns of late gadolinium enhancement in 94 patients with AL or transthyretin cardiac amyloidosis

Background Cardiac MRI (CMR) is increasingly used to further investigate patients in whom amyloidosis is suspected on echocardiography. Late gadolinium enhancement (LGE) reflects expansion of the interstitium, and circumferential subendocardial LGE has been reported to be a typical finding in AL amyloidosis; by contrast, a more diffuse transmural LGE pattern has been associated with ATTR (transthyretin amyloidosis).

Treatment strategies for chronic stable angina

Introduction: Stable angina pectoris – generally the expression of an imbalance between myocardial oxygen demand and supply – is often the first manifestation of ischemic heart disease. The effective management of this highly prevalent condition is largely dependent on the identification of the prevailing pathogenic mechanism, the implementation of lifestyle changes and the appropriate use of pharmacological agents and revascularization techniques. There is abundant literature on management of chronic stable angina, but publications are generally devoted to focused areas. There is a need for a comprehensive review that addresses both the different types of angina and their pathogenic mechanisms, as well as rational approaches to patient management. Areas covered: This paper reviews the pathogenesis and pathophysiological mechanisms of myocardial ischemia, along with its consequences and current treatment options. Relevant papers in the English literature were identified via PubMed, using the following keywords relating to chronic stable angina: ischemic heart disease, coronary artery disease and antianginal therapy. Expert opinion: The treatment of chronic stable angina has improved in recent years as a result of a better understanding of its pathogenic mechanisms, the implementation of lifestyle changes and aggressive management of risk factors, as well as pharmacological advances and better revascularization techniques. Understanding the pathogenesis of the disease is important to identify effective treatment strategies. A careful clinical history, the implementation of appropriate diagnostic tests and a rational use of antianginal drugs and revascularization protocols often ensure the successful control of the patients symptoms.

Senile cardiac amyloidosis: an underappreciated cause of heart failure

This case presents a patient with biopsy-proven, wild-type transthyretin (TTR) senile amyloidosis. The case was that of a man in his early 70s who presented with gradually progressive symptoms and signs of heart failure. The recent history included an episode of severe pancreatitis secondary to cholelithiasis and subsequently (and incidentally) noted hepatomegaly and marked ascites. Further evaluation of the aetiology of the heart failure, through echocardiography, coronary angiography and endomyocardial biopsy, led to an exact diagnosis of SSA. The patient is being treated with conventional heart failure medications while consideration is given to the use of diflusinal as an antiamyloidogenic small molecular stabiliser of TTR. Monitoring and further management advice are being coordinated by the National Amyloidosis Centre.

Hard to swallow: atypical transthyretin amyloid neuropathy mistaken for CIDP

In April 2009, a 59-year-old Afro-Caribbean man gave a 6-month history of progressive unsteadiness and falls. He reported heavy legs, tiredness on walking and painless paraesthesia below the knees. There were cramps in his hands, with weakness when attempting to open jars. He had a previous diagnosis of achalasia, for which he had sought medical attention 1 year before developing neurological symptoms. He had reported dysphagia to solids and liquids, with 10 kg weight loss. Barium swallow showed barium hold up in the distal oesophagus, tapering to a beak-like appearance. Oesophageal manometry showed elevated lower oesophageal sphincter pressure, with failure to relax on swallowing, consistent with achalasia. This was managed with two cycles of botulinum toxin injections to the lower oesophageal sphincter and oesophageal dilatation, initially with good results. He took ferrous sulfate for an unspecified anaemia. There was no toxin exposure or alcohol overuse, but he smoked marijuana occasionally. There was no relevant family history. On examination, there was wasting below the knees and in the small hand muscles, with distal symmetrical weakness. He had only a flicker of movement in the hallux and small muscles of the hands and mild weakness of movements around the ankle and finger extensors. He was areflexic. Sensory examination showed ‘stocking-and-glove’ sensory loss to light touch; vibration sense was present at the ankles, but proprioception present only for large movements of the hallux. Pinprick sensation was normal. General examination was normal. Nerve conduction studies showed a severe sensorimotor polyneuropathy, which …

PATTERNS OF LATE GADOLINIUM ENHANCEMENT PREDICT SURVIVAL IN CARDIAC AMYLOIDOSIS: A SYSTEMATIC REVIEW OF 95 CASES WITH AL OR TTR TYPE

Results: The mean age was 69.2 ± 11.3 years with male predominance (73%). Amyloid type was AL in 39 patients (41%) and ATTR in 56 patients (59%). LGE was evident in all ATTR patients and 36 AL patients (92%, p<0.01). Fifty-three ATTR patients (95%) demonstrated ≥ 1 transmural segment, compared to 12 AL patients (31%, p<0.01). Circumferential transmural LGE was specific to ATTR (6 patients (10.7%), p<0.01). Right ventricular (RV) LGE was present in all ATTR patients but only 26 AL patients (67%, p <0.01). Circumferential subendocardial LGE was present in only 8 AL patients (21%) and 2 ATTR patients (3%, p <0.01). Median survival was significantly reduced in AL patients (24 vs 36 months, p<0.01). However, the presence of transmural LGE in any segment was associated with improved survival in AL amyloid (p=0.04).

Cardiac involvement in cardiac AL amyloidosis as measured by equilibrium contrast cardiovascular magnetic resonance

Background Involvement of the heart drives prognosis in Systemic AL Amyloidosis, predicting outcome and influencing therapeutic options. Current methods of cardiac assessment do not allow formal quantification of the amyloid load. We used Equilibrium Contrast Cardiovascular Magnetic Resonance (EQ-CMR) to measure the interstitial compartment of the heart by measuring the myocardial contrast volume of distribution, VDm.