Bert-Ove Olofsson

Progression of cardiomyopathy after liver transplantation in patients with familial amyloidotic polyneuropathy, Portuguese type

BACKGROUND Transthyretin amyloidosis is today an accepted indication for orthotopic liver transplantation (OLT). For several mutations progression of the cardiomyopathy has been observed after OLT. The aim of this study was to assess the course of cardiac involvement in Swedish familial amyloidotic polyneuropathy (FAP), Portuguese type, after OLT. By comparison of the echocardiographic findings before OLT with those obtained after, the course of the heart involvement was followed. METHODS Twenty-three patients, who had undergone OLT and were examined with echocardiography 1-12 months before OLT, were available for the study. Twenty-one patients were examined 12-27 months after OLT, and 12 were re-examined 52-71 months after OLT. Two-dimensional and M-mode echocardiography were performed in accordance with the standards of the American Society of Echocardiography. RESULTS A significantly increased septal and left ventricular posterior wall thickness and a significantly increased left atrial dimension was observed at the post-OLT examinations, indicating a progression of the amyloid heart disease. This increase of the cardiac involvement was neither correlated to waiting time for OLT or to pre-operative signs of cardiomyopathy. CONCLUSIONS Even though the production of the amyloidogenic-mutated transthyretin is stopped by OLT, the cardiomyopathy may progress after the operation even for the Portuguese type of FAP. The increase of the septal and left ventricular posterior wall thickness after OLT is not restricted to patients with signs of left ventricular hypertrophy before the transplantation. The findings have important implications for the follow-up of FAP patients after OLT.

Atenolol in Secondary Prevention after Stroke

This study investigated the effect of 50 mg atenolol in reducing the risk of death, stroke and myocardial infarction after stroke and transient ischaemic attacks (TIA). The study was designed as a Swe

Liver transplantation does not prevent the development of life-threatening arrhythmia in familial amyloidotic polyneuropathy, Portuguese-type (ATTR Val30Met) patients

Background. Orthotopic liver transplantation (OLT) is today the only available treatment to halt the progress of familial amyloidotic polyneuropathy (FAP). Because heart arrhythmia and conduction disturbances are well-known manifestations of FAP, the aim of this study was to investigate the occurrence and development of heart conduction and rhythm disturbances in Swedish FAP patients who underwent liver transplantation. Methods. Ambulatory 24-hour electrocardiography (ECG) recordings (Holter-ECGs) were available from 30 patients, who had been investigated before and reexamined after OLT. Results. The number of patients with abnormalities on their ECG recordings increased after OLT. Four patients developed serious arrhythmia after transplantation that necessitated the insertion of a pacemaker 40 months or longer after OLT. Conclusions. The development of cardiac conduction disturbances and arrhythmias appear not to be halted by liver transplantation, indicating that the physician should be aware of the potential risk for FAP patients receiving transplants to develop fatal arrhythmia. The follow-up after liver transplantation should include Holter-ECG recordings.

Ischemic Stroke Impact of a Recent Myocardial Infarction

BACKGROUND AND PURPOSE The risk of ischemic stroke is increased after a myocardial infarction. We quantified the stroke risk and evaluated ischemic stroke characteristics after an acute myocardial infarction. METHODS A case-control study including patients with first-ever stroke was undertaken. Cases (n=103) were recorded prospectively in the population-based Northern Sweden World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study. Two controls per case with a stroke but without a recent myocardial infarction were matched for age, sex, and year of stroke onset. RESULTS The sudden onset of neurological symptoms (76.7% versus 54.9%, P<0.001), impairment of consciousness (35.0% versus 18.4%, P<0.01), and a progression in neurological deficits (19.4% versus 8.7%, P<0.01) were more common in cases, while the onset of stroke during sleep was rarer in cases (6.8% versus 21.4%, P<0.01). In cases and controls, the clinical subclasses of stroke were as follows: total anterior circulation infarcts, 51.5% versus 37.9% (P<0.05); partial anterior circulation infarcts, 28.2% versus 26.7% (P=NS); lacunar infarcts, 4.8% versus 27.2% (P<0.001); and posterior circulation infarcts, 15.5% versus 8.2% (P=0.051). During the first 28 days after myocardial infarction, the daily rate of stroke declined rapidly from approximately 9 to 1 stroke per 10 000 myocardial infarction patients compared with an age-adjusted average daily stroke rate of 0.14 per 10 000 in the MONICA population. CONCLUSIONS We conclude that the clinical characteristics of the stroke differ between patients with and without a recent myocardial infarction. The risk of a first-ever ischemic stroke is highest during the first few days after a myocardial infarction, but it then declines rapidly, and the absolute number of stroke events is low.

Myocardial hypertrophy and function are related to age at onset in familial amyloidotic polyneuropathy

Heart complications are frequently encountered in hereditary transthyretin amyloidosis. Lately, reports of late onset familial amyloid polyneuropathy (FAP) cases presenting with a phenotype similar to that observed in senile systemic amyloidosis have emerged. The aim of the present study was to evaluate morphological and functional features of the heart by echocardiography including myocardial strain measurements, and to compare the outcome for early with those of late onset FAP cases. Eighty-one biopsy and genetically proven FAP, ATTR Val30Met patients were investigated with two-dimensional, M-mode echocardiography and myocardial strain with special attention to inter-ventricular septum (IVS) thickness. IVS thickness was closely related to the age at onset (P < 0.0001), but not to duration of disease. Seventeen percent of the patients had severe left ventricular hypertrophy (IVS > 15 mm). These patients were all late onset cases and represented 39% of all of the late onset cases. Strain measurements were also closely related to IVS thickness and age at onset thereby signifying a decreased function of the heart muscle in late onset cases. From the present investigation it appears that late onset Swedish FAP-cases more readily develop cardiomyopathy with an increased IVS thickness. Different pathways for amyloid formation in the heart may operate in early and late onset cases.

Electrophysiologic evaluation of the cardiac conduction system and its autonomic regulation in familial amyloid polyneuropathy

A high incidence of cardiac conduction disturbances is a salient feature in familial amyloid polyneuropathy (FAP) and amyloid infiltration of the conduction system has been found. In patients with FAP autonomic nervous dysfunction involving gastrointestinal, urogenital and cardiovascular systems has been described. However, the present study is the first to evaluate the results of autonomic tests and pharmacologic intervention in the autonomic nervous regulation of the cardiac conduction system during an invasive electrophysiologic study. Seven patients with FAP and severe disturbances of the conduction system, evaluated concerning indications for pacemaker treatment, were studied; in 3 of them the parasympathetic regulation was found to be abolished. In 1 patient the observations indicated either vagal overactivity or denervation oversensitivity of the receptors. The function of the beta adrenoceptors was intact in all patients, but a disturbance of sympathetic innervation could not be excluded. Dysfunction of autonomic nervous regulation of the cardiac conduction system was thus found in 4 of 7 patients. However, most conduction abnormalities were irreversible, indicating amyloid infiltration of the conduction system as the predominant pathophysiologic mechanism, in accordance with the findings of pathoanatomic studies.

Impact of liver transplantation on autonomic neuropathy in familial amyloidotic polyneuropathy: An evaluation by spectral analysis of heart rate variability

Suhr OB, Wiklund U, Ando Y, Ando E & Olofsson B‐O (Umeå University Hospital, Umeå, Sweden). Impact of liver transplantation on autonomic neuropathy in familial amyloidotic polyneuropathy: an evaluation by spectral analysis of heart rate variability. J Intern Med 1997; 242: 225–9.

Autonomic neuropathy in familial amyloidotic polyneuropathy

ABSTRACT— Familial amyloidotic polyneuropathy (FAP) is characterized by both sensimotor and autonomic dysfunction. Autonomic disturbance involving the gastrointestinal tract, the urinary bladder, the cardiac conduction system, and the peripheral circulation has been described. In this study simple, non‐invasive tests of autonomic function based on heart rate variability were applied to 12 patients with FAP and 12 healthy volunteers. The heart rate variation during normal breathing, deep breathing and during tilt from recumbent to standing position was measured. All tests showed significantly less heart rate variation in patients than in controls and the heart rate variation decreased with increasing severity of neurological disability, but the small number of patients in our study does not allow any further comparison between subgroups. Our study thus indicates impaired cardiovascular autonomic function in patients with FAP and we believe that these findings might also be of importance in other forms of systemic amyloidosis.

Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1

Abstract.  Mörner S, Lindqvist P, Mellberg C, Olofsson B‐O, Backman C, Henein M, Lundblad D, Forsberg H (Umeå University Hospital, Umeå; Umeå University, Umeå; Sunderby Hospital, Luleå; Sweden). Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1. J Intern Med 2010; 268:59–65.

Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or both?

BACKGROUND Myotonic dystrophy type 1 (DM1) is a systemic disease which affects the heart and may be a cause of sudden death. Conduction disturbances are the major cardiac abnormalities seen in this condition. We sought to assess electrical and mechanical cardiac functions to identify abnormalities that might explain sudden cardiac death in DM1. METHODS Thirty six patients with DM1 and 16 controls were studied using echocardiography including myocardial Doppler. ECG recordings were also obtained. RESULTS Left ventricular (LV) dimensions were maintained but systolic function was reduced (p<0.001), including stroke volume (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was significantly asynchronous demonstrated by prolonged total isovolumic time (t-IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min (upper 95% normal CI), 13 of whom had PR≥200 ms, 11 had QRS duration>120 ms (5 had combined abnormality) and the remaining 5 had neither. Over the 3 years follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6 patients, PR interval in 4 and QRS duration in one. CONCLUSIONS In DM1 patients, LV conventional measurements are modestly impaired but cardiac time relations suggest marked asynchronous cavity function. Although our findings were primarily explained on the basis of long PR interval or broad QRS duration a minority presented an evidence for myocardial cause of asynchrony rather than electrical. Early identification of such abnormalities may guide towards a need for additional electrical resynchronization therapy which may improve survival in a way similar to what has been shown in heart failure trials.