Simon W Dubrey

Mode of death in patients with newly diagnosed heart failure in the general population.

Early prognosis for incident (new) heart failure (HF) patients in the general population is poor. Clinical trials suggest approximately half of chronic HF patients die suddenly but mode of death for incident HF cases in the general population has not been evaluated.

Amyloid Heart Disease

The systemic amyloidoses are an uncommon group of disorders characterized by the extracellular deposition of amyloid in one or more organs. Cardiac deposition, leading to an infiltrative/restrictive cardiomyopathy, is a common feature of amyloidosis. It may be the presenting feature of the disease or may be discovered while investigating a patient presenting with non-cardiac amyloidosis. In this article we review the features of cardiac amyloidosis and its varied manifestations. The need for a high index of suspicion and the critical importance of precise biochemical typing of the amyloid deposits is stressed in light of recent advances in therapy which can, when appropriately used, significantly improve prognosis.

Progression of ventricular wall thickening after liver transplantation for familial amyloidosis.

BACKGROUND Familial amyloidosis (FAP) is characterized by the progression of neurologic and cardiac impairment ultimately leading to death within 7 to 15 years after the onset of the disease. Liver transplantation represents the only definitive therapy for this disease and has been performed since 1990. METHODS To determine the effect of liver transplantation on disease progression, electrocardiography and Doppler echocardiography were performed and blindly analyzed on 11 patients with FAP who were followed 0.8 to 8.6 years before liver transplantation and 0.8 to 4.1 years after liver transplantation. RESULTS; After liver transplantation, five patients showed progression of left ventricular wall thickening with increased left ventricular mass, and three of these five showed a reduction in electrocardiographic voltage despite abolition of the mutant protein from the serum. Of the five patients showing progressive wall thickening, four had the transthyretin variant Glu 42 Gly and one patient had the Ala 36 Pro variant; none of the remaining six patients, all of whom possessed the Val 30 Met variant, showed echocardiographic changes. Although 9 of the 11 patients have shown symptomatic improvement in neurologic symptoms, 1 patient has developed heart failure and a second patient has suffered a sudden cardiac death. CONCLUSIONS After liver transplantation, patients with FAP should have regular clinical evaluations including electrocardiographic and echocardiographic examinations to look for continued deterioration in heart structure or function.

Familial and primary (AL) cardiac amyloidosis: echocardiographically similar diseases with distinctly different clinical outcomes.

OBJECTIVE: To determine whether patients with myocardial amyloidosis due either to AL (primary) amyloid or familial amyloid have distinguishing echocardiographic or electrocardiographic features; and to compare the prevalence of heart failure and survival in the two types of amyloidosis in relation to echocardiographic findings. DESIGN: Blinded group comparison of randomly selected cases of cardiac amyloidosis. SETTING: International referral centre for amyloid research and treatment. PATIENTS: 36 patients with cardiac amyloid heart disease, of whom 12 had familial and 24 had primary AL amyloidosis. RESULTS: Familial and AL echocardiograms were morphologically indistinguishable, with similar left ventricular wall thickness, mean (SD) 15.4 (2.3) nu 15.8 (2.5) mm, respectively; right ventricular wall thickness was also similar between amyloid types: 9.6 (2.8) nu 9.7 (6.5) mm, respectively. Doppler indices of left and right ventricular function, left ventricular volume, and ejection fraction were also similar. Low voltage electrocardiograms (< 0.5 mV) were more common in the AL (16/24, 67%) than in the familial group (4/12, 25%), P < 0.05. The one year survival for familial and AL forms was 92% (11/12) nu 38% (6/24), respectively, with virtually all deaths due to cardiac causes. CONCLUSIONS: Although cardiac involvement is echocardiographically indistinguishable, cardiac mortality is very different between the two forms of amyloidosis. Preservation of electrocardiographic voltage in familial amyloidosis suggests that the particular biochemical characteristics of distinct types of amyloid fibril have different pathological effects on the myocardium. This distinction becomes critical in the evaluation, treatment, and management of patients who have a diagnosis within the spectrum of the protein deposition diseases.

Effect of orthotopic liver transplantation on the progression of familial amyloidotic polyneuropathy.

BACKGROUND Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protein transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ultimately, death. The majority of TTR is produced in the liver, and transplantation of the liver has been shown to ameliorate this source of mutant TTR, arresting the progression of this fatal disease. METHODS Thirteen patients with FAP have undergone successful liver transplant surgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow-up are excluded from the analysis. RESULTS Ten of 13 patients (77%) remain alive an average of 49 months (range, 17-64 months) after transplantation. Three patients suffered sudden death, with autopsy documentation of amyloid deposits involving the conduction system of the heart. Liver transplantation was performed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis. Neurological and nutritional symptoms improved in the majority of affected patients. Those patients with echocardiographic evidence of ventricular wall and valve thickening before transplantation progressed postoperatively despite neurologic improvement. CONCLUSIONS Liver transplantation offers the only cure for the genetic defect causing FAP and appears to result in subjective and objective improvement in neurological dysfunction. Patients with preexisting cardiovascular abnormalities progress despite transplantation; therefore, consideration for combined heart-liver transplantation may be warranted in this subset of patients.

Diagnosis and Management of Cardiac Sarcoidosis

Cardiac sarcoidosis is an underdiagnosed disease that may be present in as many as 25% of patients with systemic sarcoidosis. Although most commonly recognized in patients with other manifestations of sarcoidosis, it may occur in isolation and its presence is often not appreciated. Cardiac sarcoidosis may present as asymptomatic left ventricular dysfunction, congestive heart failure, atrioventricular block, atrial or ventricular arrhythmia and sudden death. Although untested in clinical trials, early use of high-dose steroid therapy may halt or reverse cardiac damage. This article reviews the clinical manifestations, diagnosis and treatment of sarcoidosis, with an emphasis on new imaging techniques and therapies.

A randomized trial of home telemonitoring in a typical elderly heart failure population in North West London: results of the Home-HF study

Heart failure chiefly affects the elderly, with frequent emergency admissions. Telemonitoring can identify worsening heart failure but previous randomized trials have enrolled selected patient populations. The Home‐HF study examined the impact of home telemonitoring on typical heart failure patients discharged from three acute hospitals in North West London, UK.

Amyloid diseases of the heart: assessment, diagnosis, and referral

The amyloidoses are a group of diseases in which amyloid, a proteinaceous substance, deposits in one or more organs. As many as 23 different precursor proteins to the formation of amyloid have been described in man. These may deposit themselves in a fibrillar matrix within selected tissues. Fibrils are formed when normally soluble constituents undergo transformational change and misfold to become relatively insoluble. A variety of mechanisms promote these changes, which result in the final common pathway of the deposition of non-branching fibrils that can be visualised by electron microscopy and which are seen on light microscopy as a homogenous extracellular material (figure 1). Figure 1 Myocardial biopsy from a patient with congestive cardiac failure and echocardiographic appearances of amyloid deposition. The myocytes appear yellow with the amyloid staining turquoise (sulfated Alcian blue stain). Immunostaining subsequently confirmed transthyretin as the constituent protein. In the developed world, cardiologists predominantly encounter three main types of amyloidosis that affect the heart; light chain (AL) amyloidosis, senile systemic amyloidosis (SSA), and familial amyloidosis (FAP); the latter most commonly results from a mutation in transthyretin. In the developing world, secondary amyloid (AA) is more prevalent, due to chronic infections and inadequately treated inflammatory conditions. Occurring worldwide and later in life, a further amyloid type to affect the heart is isolated atrial amyloid (IAA).w1 w2 Finally, and much less common, are the non-transthyretin variants, including mutations of fibrinogen, apoprotein, and gelsolin. These rarer types can cause significant cardiac compromise. Cardiac involvement in amyloidosis is usually part of a systemic disease. The heart is frequently the predominant organ affected but, in some forms of the disease, isolated heart involvement can occur. In patients with a non-cardiac biopsy showing amyloid deposition, cardiac involvement has been defined—by a consensus opinion from the 10th International Symposium on Amyloidosis1—as …

Long term results of heart transplantation in patients with amyloid heart disease

OBJECTIVE To determine the outcome of heart transplantation for end stage amyloid heart disease in patients treated at a single centre. DESIGN Records of all patients with amyloid heart disease who underwent heart transplantation were examined to determine survival, graft involvement by amyloid, the course of systemic amyloid disease, and the cause of death. PATIENTS 10 patients, mean (SD) age 54 (8) years, received transplants in the 13 year period 1984 to 1997. RESULTS Two patients, both with AL amyloid (primary systemic amyloidosis), died perioperatively. Mean follow up in the remaining eight patients was 49.9 (39.5) months (range 3–116 months). Amyloid deposits in the grafts became evident histologically in five patients with AL amyloid at 5, 11, 12, 28, and 30 months after transplantation, and in one patient with familial amyloid at 60 months. Echocardiography showed no evidence of left ventricular systolic impairment at the time of recurrence. Seven patients died, at 3, 11, 26, 32, 49, 85, and 116 months after transplantation; four of these deaths were related to amyloidosis. Actuarial survival at one and two years was 60% and at five years, 30%. CONCLUSIONS Heart transplantation for amyloid heart disease remains controversial because of the scarcity of hearts for transplantation, the systemic nature of amyloidosis, and the potential for amyloid deposition in the graft. Postoperative mortality was high (20%), reflecting extracardiac amyloid. Heart transplantation for end stage cardiac amyloidosis is feasible but, without treatment of the underlying process, it is a palliative procedure.

Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation.

Thrombus formation in the left atrium is rare in patients in sinus rhythm. In three patients with extensive cardiac amyloidosis transthoracic echocardiography showed large atrial thrombi in or protruding into the body of the left atrium during sinus rhythm. Doppler studies showed no A wave on mitral inflow. Severe atrial and ventricular infiltration by amyloid may have resulted in mechanical atrial standstill with resultant thrombus formation. These findings suggest that patients with severe cardiac amyloidosis may require anticoagulation when atrial function is impaired.