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.

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.

Swedish familial systemic amyloidosis with polyneuropathy (FAP) depends on a mutation leading to a methionine-for-valine substitution in transthyretin. The disease appears with different clinical manifestations, including age of onset and involvement of the heart. Liver transplantation is currently the only curative treatment, but progressive cardiomyopathy may occur post-transplant. Two amyloid deposition patterns have previously been described in the heart. In one, the amyloid consists partially of transthyretin fragments and is weakly stainable by Congo red, while in the other, only full-length molecules are found and the fibrils have a strong affinity for Congo red. The present study aimed to see whether these morphological and biochemical variations have clinical implications. Subcutaneous adipose tissue biopsies were taken from 33 patients with Val30Met FAP and examined by microscopy, electrophoresis and western blot. Clinical data included age, sex, duration of disease and echocardiographic determination of the interventricular septum (IVS) thickness. It was found that fibrils composed of only full-length transthyretin were associated with early age of onset (44.8 +/- 12.9 years), no clinical cardiac involvement and a strong affinity for Congo red. In contrast, presence of transthyretin fragments in the amyloid was associated with late age of onset (67.3 +/- 7.0 years), signs of cardiac involvement and weak Congo red staining. For each individual, the same molecular type of amyloid was found in different organs. This is the first report showing that variations in clinical appearance of familial ATTR amyloidosis are associated with specific structural differences in the amyloid fibrils, and therefore may have a molecular cause. The molecular type of amyloid can be determined from a subcutaneous fat tissue biopsy. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

OBJECTIVES:Cardiomyopathy is a well known complication in familial amyloidotic polyneuropathy (FAP). Troponin T and B-natriuretic peptide (BNP) have been shown to be excellent markers for heart complications in AL-amyloidosis. The aim of the study was to investigate troponin T, troponin I and BNP as markers for myocardial damage and failure in FAP. DESIGN:Retrospective investigation of patients with FAP. SETTING:Tertiary referral centre. SUBJECTS:Twenty-nine patients who had been submitted for evaluation of FAP. INTERVENTIONS:Two-dimensional M-mode and Doppler echocardiography and strain echocardiographic examination. Measurement of Troponin T, troponin I and BNP. RESULTS:Troponin T was detectable in only three patients who all had abnormal interventricular septal (IVS) thickness. Troponin I was abnormal in six patients (21%), of which only two had an increased IVS thickness. The heart function was generally well preserved in the patients in spite of hypertrophy of the IVS in 14 patients. BNP was elevated in 22 patients (76%), and it correlated significantly with IVS thickness and basal septal strain. CONCLUSIONS:Transthyretin amyloid seems to be less harmful to myocytes than that of AL amyloid as evaluated by serum troponin T and I as well as by echocardiography. BNP appears to be a sensitive marker for cardiomyopathy in FAP, and could prove valuable for follow-up purposes as has been shown for AL-amyloidosis patients.

Background: Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis with cardiac involvement. As early identification of the cardiac involvement is of major clinical interest we performed this study to test the hypothesis that tissue Doppler imaging (TDI) and strain imaging (SI) might disclose cardiac involvement in patients with early stages of FAP.Methods: Twenty-two patients with FAP and 36 healthy controls were studied. Standard M-mode and Doppler echocardiography were performed. TDI and SI were used to assess the regional longitudinal left ventricular (LV) lateral and septal and right ventricular (RV) watt functions. All time intervals were corrected for heart rate by dividing with R-R interval and presented as percentage.Results: We found that patients in comparison with controls had increased LV and RV wall thickness and by using TDI a prolonged isovolumic relaxation time (IVRt) at the septal segment (15.0 +/- 7.0 vs 10.7 +/- 4.1%, p < 0.05) and prolonged isovolumic contraction time (IVCt) at LV lateral (12.8 +/- 4.3 vs 10.1 +/- 3.3%, p < 0.05), septal (12.5 +/- 3.5 vs 8.9 +/- 1.9%, p < 0.001) and RV free wall segments (12.0 +/- 3.6 vs 8.3 +/- 2.1%, p < 0.001). Strain was reduced at LV lateral basal segment (-4.6 +/- 14.0 vs -20.2 +/- 9.1, p < 0.001), RV free wall mid segment (-16.2 +/- 12.8 vs -29.4 +/- 15.2) as well as both septal segments (-4.1 +/- 11.7 vs -16.2 +/- 9.0%, p < 0.001, -8.8 +/- 11.5 vs -19.4 +/- 8.4%, p < 0.001 for septal basal and midsegment). Even in the absence of septal hypertrophy the septal strain was reduced and the regional IVCt was prolonged.Conclusions: This is the first clinical study using TDI and strain in patients with FAP showing functional abnormalities before any morphological echocardiographic abnormalities were present. Both the left and right heart functions are involved and the disease should therefore be regarded as biventricular. (C) 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

Summaryobjectives To assess effects of GH replacement therapy on cardiac structure and function, exercise capacity as well as serum lipids in elderly patients with GH deficiency (GHD).patients and methods Thirty‐one patients (six females, 25 males), aged 60–79 years (mean 68 years) with GHD on stable cortisone and thyroxine substitution were studied. All men with gonadotropin deficiency had testosterone and one woman had oestrogen replacement. They were randomized in a double‐blind manner to GH or placebo treatment for 6 months, followed by another 12 months GH (Humatrope, Eli Lilly & Co, Uppsala, Sweden). GH dose was 0·017 mg/kg/week for 1 month and then 0·033 mg/kg/week divided into daily subcutaneous injections at bedtime. Echocardiography, exercise capacity tests and serum lipid measurements were performed at 0, 6, 12 and 18 months.results During the 6‐month placebo‐controlled period there were no significant changes in the placebo group, but in the GH‐treated group there was a significant increase in IGF‐I to normal levels for age, with median IGF‐I from 6·9 to 18·5 nmol/l, increase in resting heart rate and maximal working capacity. During the open GH study, IGF‐I increased from 8·7 to 19·2 nmol/l at 6 months and 18·8 nmol/l at 12 months (P ≤ 0·001). At 6 months, in the open GH study group, a minor decrease in aortic outflow tract integral (VTI) from 21·8 to 20·7 cm (P = 0·031) and an increase in heart rate at rest from 63 to 67 bpm (P = 0·017), heart rate at maximum exercise from 138 to 144 bpm (P = 0·005) and maximum load at exercise from 142 to 151 Watts (P = 0·014) were seen. These changes were temporary and returned at 12 months with no significant difference from baseline values. Left ventricular dimensions and blood pressure showed no significant changes. At 6 months, in the open GH study group, there was a significant decrease in serum low‐density lipoprotein (LDL) cholesterol from 3·7 to 3·4 mmol/l (P = 0·006), a decrease in LDL/HDL ratio from 3·4 to 3·1 (P = 0·036) and a decrease in serum total cholesterol from 5·6 to 5·3 mmol/l (P = 0·036). At 12 months, serum lipids showed same changes with a significant decrease in serum LDL cholesterol (P = 0·0008), in LDL/HDL ratio (P = 0·0005) and in serum total cholesterol (P = 0·049). Serum HDL cholesterol showed no significant change at 6 months, at 12 months a significant increase was seen from 1·2 to 1·4 mmol/l (P = 0·007). There were no significant changes in serum triglycerides.conclusions GH substitution to elderly patients with GHD caused only a transient increase in heart rate. At the end of the 12 months there were no significant changes on cardiac noninvasive structural and functional parameters. Maximal working capacity transiently improved. Thus, the therapy was safe without negative effects on cardiac structural and functional noninvasive parameters. Lipid profiles improved with reduction of serum LDL cholesterol accompanied by significant improvement of LDL/HDL ratio and serum HDL cholesterol after 12 months treatment.

OBJECTIVE To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. METHODS Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE-selectin). RESULTS Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. CONCLUSION Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels.

The effects of anaesthesia for major abdominal vascular surgery on coronary flow regulation and mechanisms of myocardial ischaemia were studied in 56 patients with CAD, using a randomized, partly double–blinded protocol. After induction with fentanyl (3 μg–kg‐1) and thiopentone (2–4 mg kg‐1) and tracheal intubation, principal anaesthetics were nitrous oxide/oxygen (60/40) with isoflurane (n = 20), halothane (n = 19) or fentanyl (15–20 μg kg‐1) (n = 17). Conventional invasive techniques and coronary venous retrograde thermodilution were used to assess systemic and coronary haemodynamics. Coronary vascular resistance was estimated from myocardial oxygen extraction. Myocardial ischaemia was diagnosed by 12–lead ECG and/or anterior wall motion abnormalities by cardiokymography and/or myocardial lactate production. When adjustment of anaesthetic dose was insufficient for haemodynamic control, iv phenylephrine and nitroglycerine were adminstered to treat hypotension and hypertension or cardiac failure respectively. Measurements were performed at four specific intervals; awake, before surgery and 10 and 30 min after abdominal incision.Comparable changes of systemic haemodynamics and myocardial oxygen consumption were observed in the three groups. Coronary vasodilation was evidenced in isoflurane patients only and was linearly dose–dependent (P < 0.001). Partial Least Squares Projections to Latent Structures modelling with cross validation confirmed this dose–dependency and ruled out a clinically measurable influence by intervention drugs or simultaneous systemic haemodynamic abnormalities.The incidence of myocardial ischaemia during anaesthesia and surgery was comparable in the three groups (35, 37 and 24%, respectively) and there was an association with systemic haemodynamic aberrations in 19 of the 27 ischaemic episodes. In contrast to ischaemic halothane and fentanyl patients, isoflurane patients with ischaemia had significantly lower myocardial oxygen extraction (P = 0.008 and P = 0.001, respectively), indicating that the oxygen extraction reserve was not utilized in a normal way during ischaemia.

This study examines the effects of nitrous oxide on haemodynamics, anterior left ventricular (LV) function and incidence of myocardial ischaemia in abdominal vascular surgical patients with coronary artery disease. Forty-seven patients were randomly assigned to isoflurane-fentanyl anaesthesia with nitrous oxide-oxygen vs air-oxygen (control). Systemic and coronary haemodynamics, 12-lead ECG, LV anterior wall motion by cardiokymography (CKG) and myocardial lactate balance were recorded at four intervals: before and during anaesthesia and 10 and 30 minutes into surgery. Systemic haemodynamics were controlled by anaesthetic dose, and, when insufficient, by i.v. nitroglycerine (NG) in case of LV failure (PCWP > 18 mmHg) and by phenylephrine during hypotension. We found that nitrous oxide was associated with greater need for i.v. nitroglycerin (patients: P = 0.031, episodes P = 0.005) and more myocardial ischaemia (patients P = 0.012, episodes P = 0.001) despite systemic and coronary haemodynamics comparable to the control group. We conclude that nitrous oxide, known to have both sympathomimetic and cardiodepressive actions, produced cardiodepression in the face of sympathetic stimulation. Our study design did not allow to conclude if myocardial ischaemia was the consequence of increased wall stress or a reason for the observed LV dysfunction. The higher incidence of introperative myocardial ischaemia and need for NG did not cause increased cardiac morbidity.

Cerium-labeled microspheres were used for blood-flow measurements in 7 New Zealand white rabbits with exercise-induced chronic Achilles paratenonitis and tendinosis. The blood flow increased 1.9 times more on the exercised side as compared with the contralateral, unexercised (control) side with respect to both the tendon and the paratenon. The blood flow of the tendon of the exercised leg showed a strong correlation with the blood flow in the paratenon of the ipsilateral side (r = 0.81). We concluded that the relative contribution of blood from the paratenon to the tendon remained unaltered in the exercised tendon and that degeneration of the tendon cannot be primarily explained by chronic circulatory impairment.

In a controlled, retrospective, clinical study, the relationships between traumatic digital amputation, digital replantation, and cold intolerance were investigated. The results of the investigation indicate that cold intolerance is a major reason for disability after digital amputation. They also indicate that the cold intolerance experienced after digital replantation is due to the original injury, and that it is not aggravated by the reconstructive surgery. Cold intolerance, in and of itself, is not a contraindication to digital replantation, regardless of whether the patient lives or works in high- or low-temperature environments.

Twenty-two patients with the Swedish variant of familial amyloidosis with polyneuropathy were studied by M-mode and two-dimensional echocardiography. These patients had few symptoms consistent with cardiac disease but, nevertheless, echocardiograms of only two of them, both with a short history of the disease, were considered normal in all aspects. The most common abnormality was increased thickness of the interventricular septum found in 20 (91%) of the patients. This septal hypertrophy was asymmetric in 12 (55%) of them. Two-dimensional echocardiography revealed a characteristic hyperrefractile appearance of the myocardium in 15 (68%) of the patients. Thus, echocardiography showed a characteristic pattern in these patients. This study also indicates that cardiac amyloidosis can be diagnosed in the preclinical, asymptomatic state by M-mode and two-dimensional echocardiography.