Paavo Uusimaa

Remote monitoring of implantable cardioverter defibrillator patients: a safe, time-saving, and cost-effective means for follow-up

Aims The purpose of this prospective study was to investigate whether internet-based remote monitoring offers a safe, practical, and cost-effective alternative to the in-office follow-up visits of patients with an implantable cardioverter defibrillator (ICD). Methods and results Forty-one patients (62 ± 10 years, range 41–76, 83% male) with previously implanted ICD were followed for 9 months. One-hundred and nineteen scheduled and 18 unscheduled data transmissions were performed. There were no device-related adverse events. Over 90% of the patients found the system easy to use. Physicians reported the system as being ‘very easy’ or ‘easy’ to use and found the data comparable to traditional device interrogation in 99% of the cases. They were able to address all unscheduled data transmissions remotely. Compared with the in-office visits, remote monitoring required less time from patients (6.9 ± 5.0 vs. 182 ± 148 min, P < 0.001) and physicians (8.4 ± 4.5 vs. 25.8 ± 17.0 min, P < 0.001) to complete the follow-up. Substitution of two routine in-office visits during the study by remote monitoring reduced the overall cost of routine ICD follow-up by 524€ per patient (41%). Conclusion Remote monitoring offers a safe, feasible, time-saving, and cost-effective solution to ICD follow-up.

Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency.

BACKGROUND Left ventricular function after acute myocardial infarction (AMI) is determined by the expansion of the infarct zone and remodeling of the noninfarcted myocardium. An occluded infarct-related artery (IRA) is an independent risk factor for remodeling. METHODS AND RESULTS Changes in myocardial collagen metabolism were evaluated in 36 patients with suspected AMI. The plasma creatine kinase MB fraction and myoglobin release curves were analyzed for assessment of early reperfusion and infarct size. Collagen scar formation was evaluated by measurement of serum concentrations of the aminoterminal propeptide of type III procollagen (PIIINP), the aminoterminal propeptide of type I procollagen (intact PINP), and the carboxyterminal propeptide of type I procollagen (PICP). Plasma renin activity and urine excretion of cortisol and aldosterone were also measured. Coronary angiography and left ventricular cineangiography were performed during early hospitalization. The serum concentration of PIIINP increased from 3.50+/-0.20 to a maximum of 5.08+/-0.36 microg/L (n=32) in the patients with AMI, whereas the concentrations of intact PINP and PICP tended to decrease. The area under the curve (AUC) of PIIINP during the first 10 postinfarction days was larger in patients with severe heart failure or ejection fractions < or = 40% than in those with no heart failure or with an ejection fraction > 40% (P<.05 and P<.01, respectively), and it was also larger in the patients with TIMI grade 0 to 2 flows than in those with TIMI 3 flows (P<.05), despite similar enzymatically determined infarct sizes. No significant correlations between PIIINP and neurohumoral parameters were observed. The AUC of PIIINP and the change in PIIINP during the first 4 days were significantly correlated with indices of cardiac function. CONCLUSIONS Collagen scar formation after AMI can be quantified by measurement of serum PIIINP concentrations. Scar formation is more prominent in large infarctions causing left ventricular dysfunction and in patients with occluded IRAs.

Plasma vasoactive peptides after acute myocardial infarction in relation to left ventricular dysfunction

We measured plasma concentrations of vasoactive peptides in 32 patients with acute myocardial infarction and evaluated their value as markers of left ventricular dysfunction. Plasma levels of atrial natriuretic peptide (ANP), the N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP) and endothelin-1 were measured serially by radioimmunoassays. The infarct size was estimated from the creatine kinase MB release curve. Coronary angiography and left ventricular cineangiography were performed in all patients during hospitalization and 6 months later in 15 patients. Myocardial infarction caused an increase in vasoactive peptides, the highest values for ANP (36.5+/-6.79 pmol/l), NT-proANP (1130+/-170 pmol/l) and endothelin-1 (9.72+/-0.68 pmol/l) being found on admission and those for BNP (56.0+/-7.13 pmol/l) on Day 2. Plasma levels of natriuretic peptides were dependent on infarct size, its location and degree of myocardial dysfunction and that of BNP also on infarct artery patency. Plasma endothelin-1 level was higher in patients with TIMI 3 than TIMI 0-2 flow. Plasma vasoactive peptides remained elevated during the 6-month follow-up period and they were dependent on the degree of myocardial dysfunction. BNP measured on any day of hospitalization showed the best correlation with ejection fraction measured during the acute phase of infarction or at 6 months. The results show that BNP is the best indicator of left ventricular dysfunction after myocardial infarction and its reliability is not dependent on the time point of measurement.

Ventricular tachyarrhythmia as a primary presentation of sarcoidosis

AIMS Sarcoidosis is a multisystem, granulomatous disease with occasional cardiac manifestations. The clinical course of patients with ventricular tachyarrhythmias as a primary presentation of sarcoidosis is mostly unknown. METHODS AND RESULTS We describe nine patients (four males and five females) in whom sarcoidosis manifested as ventricular tachycardia (VT). The age of the patients was 53 +/- 10 years (range 33-68). The disease was diagnosed by endomyocardial biopsy in eight patients and by lymph node biopsy in one patient. The presenting arrhythmia varied from non-sustained VT to incessant VT and ventricular fibrillation. All patients received implantable cardioverter defibrillator (ICD) and anti-arrhythmic medication. High-dose steroid treatment was used in eight cases. During the follow-up (50 +/- 34 months), five patients underwent appropriate ICD therapies and non-sustained VT episodes were detected in four patients. Two patients developed incessant VT, which was treated by catheter ablation. One patient was referred for heart transplantation. CONCLUSION Our data indicate that sarcoidosis can manifest as VT without any detectable systemic findings. This makes sarcoidosis an important diagnostic consideration in patients with VT of unknown origin. Arrhythmia control in cardiac sarcoidosis is difficult, and all modern treatments including high-dose steroids, anti-arrhythmic drugs, ICD, and catheter ablation are needed to suppress the arrhythmias.

Passive mechanical stretch releases atrial natriuretic peptide from rat ventricular myocardium.

Ventricular hypertrophy is characterized by augmentation of synthesis, storage, and release of atrial natriuretic peptide (ANP) from ventricular tissue, but the physiological stimulus for ANP release from ventricles is not known. We determined the effect of graded, passive myocardial stretch on ANP release in isolated, arrested, perfused heart preparations after removal of the atria in 13-20-month-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). By this age, ANP gene expression was increased in the hypertrophic ventricular cells of SHR, as reflected by elevated levels of immunoreactive ANP and ANP mRNA and the increased ANP secretion (SHR, 93 +/- 14 pg/ml, n = 22; WKY rats, 22 +/- 2 pg/ml, n = 20; p less than 0.001) from perfused ventricles after removal of the atria. The release of ANP from ventricles was examined at two levels of left ventricular pressure by increasing the volume of the intraventricular balloon for 10 minutes. Stretching of the ventricles produced a rapid but transient increase in ANP secretion. As left ventricular pressure rose from 0 to 14 and 26 mm Hg in WKY rats and from 0 to 13 and 27 mm Hg in SHR, increases in ANP release into the perfusate of 1.4 +/- 0.1-fold and 1.5 +/- 0.2-fold (p less than 0.05) in WKY rats and 1.1 +/- 0.1-fold and 1.6 +/- 0.2-fold (p less than 0.05) in SHR, respectively, were observed. There was a highly significant correlation between the left ventricular pressure level and the maximal concentration of ANP in the perfusate during stretching (p less than 0.001, r = 0.59, n = 42), as well as between the maximal ANP concentrations in perfusate during stretching and the ventricular weight/body weight ratios of the corresponding animals (r = 0.38, p less than 0.05, n = 42). High performance liquid chromatographic analysis revealed that the ventricles both before and during stretch primarily released the processed, active, 28-amino acid ANP-like peptide into the perfusate. These results indicate that stretching is a direct stimulus for ventricular ANP release and show that ANP is also a ventricular hormone.

Candidate locus analysis of familial ascending aortic aneurysms and dissections confirms the linkage to the chromosome 5q13-14 in Finnish families.

OBJECTIVE The purpose of the study was to carry out a candidate gene analysis in families with familial thoracic aortic aneurysms and dissections. METHODS The study material consisted of 11 Finnish families (with 115 members genotyped) who underwent echocardiographic examination for measurement of the aortic root diameter. Selected candidate genes included the loci for Marfan and Ehlers-Danlos syndromes, the genes of matrix metalloproteinases 3 and 9 and tissue inhibitor of metalloproteinase 2 as well two loci on the chromosomes 5q13-14 and 11q23.2-q24, previously found to be linked to the disease. RESULTS The chromosomal locus 5q13-14 was linked to the disease risk (nonparametric linkage score 3.0, P =.005) confirming the previous linkage. Other candidate genes and loci were excluded as major loci in these families. CONCLUSIONS The identification of the gene at chromosomal location 5q13-14 causing the development of such diseases would give us important knowledge on the pathogenesis of the disease and enable the identification of subjects at risk. This in turn would lead to appropriate treatment before the occurrence of fatal complications and, likely, to the development of new treatment methods.

Role of myocardial redox and energy states in ischemia-stimulated release of atrial natriuretic peptide

The correlations between myocardial redox and energy states and atrial natriuretic peptide (ANP) secretion were studied in the perfused rat heart by exposing the hearts to global and low-flow ischemia for varying periods. Atrial and ventricular energy states and immunoreactive ANP in the effluent perfusate were measured. The basal secretion rate of ANP was 2.7 +/- 0.2 ng/min.g dry wt and it was stimulated 2.6 +/- 0.4, 4.0 +/- 0.6, 11.2 +/- 2.1 and 13.3 +/- 3.2-fold (means +/- S.E.) at the time point of 2 min after 5, 10, 20 and 30-min periods of ischemia, respectively. The increase in ANP release during the post-ischemic period was statistically significant and showed positive linear correlation with the atrial and ventricular lactate/pyruvate ratios (r = 0.92 and 0.89, respectively) and negative non-linear correlation with the atrial and ventricular phosphorylation potentials (r = -0.97 and -0.94, respectively). In agreement with the enhanced release of ANP after global ischemia, low-flow ischemia also increased ANP release. Cellular damage was not evidently responsible for the increased secretion, because only ANP1-28, the processed form of the peptide, was detected in the perfusates and no processing of exogenous proANP during or after ischemia was observed. These results indicate that myocardial ischemia stimulates ANP release and suggest that cellular redox and energy states may be linked to ANP release during ischemia/reperfusion. Thus, ANP release during and after ischemia in vivo may be due not only to atrial distention but also to changes in energy metabolism.

Serum myoglobin/carbonic anhydrase III ratio as a marker of reperfusion after myocardial infarction

BACKGROUND Coronary patency is important for short- and long-term outcome after myocardial infarction. Serum myoglobin concentration is a sensitive marker of myocardial damage and its specificity can be improved by simultaneous measurement of carbonic anhydrase III, a skeletal muscle marker. In the present study we evaluated the role of myoglobin/carbonic anhydrase III ratio as a non-invasive marker of reperfusion. METHODS We measured myoglobin, carbonic anhydrase III and creatine kinase MB-fraction release serially in 29 patients with acute myocardial infarction treated with thrombolysis and in 28 patients treated with primary coronary angioplasty. RESULTS Thrombolytic therapy was followed by a 9.1+/-2.2-fold increase in myoglobin and 10.8+/-3.3-fold increase in creatine kinase MB-fraction during the first hour of treatment, while carbonic anhydrase III remained unchanged. The peak value of myoglobin/carbonic anhydrase III ratio was found at 2 h and that of creatine kinase MB-fraction at 8 h after thrombolysis. Knowledge of the reperfusion time point during primary angioplasty and follow-up of cardiac markers revealed that cut-off points of 3 and 10 h for the peak values of myoglobin/carbonic anhydrase III ratio and creatine kinase MB-fraction can be used as indicators for reperfusion, respectively. Myoglobin/carbonic anhydrase III ratio measured before treatment and at 2 and 4 h after the onset of treatment screened 23 of those 25 patients with probable reperfusion after thrombolysis. CONCLUSIONS We conclude that measuring myoglobin/carbonic anhydrase III ratio during the first hours after initiation of thrombolysis may be useful in evaluating the success of reperfusion after acute myocardial infarction.

Serum lipoprotein(a) level in relation to severity of coronary artery disease and coronary artery patency in acute myocardial infarction

Abstract Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle that may accelerate atherogenesis and promote thrombosis. In the present study, relationships between serum Lp(a) levels and the severity of coronary artery disease and infarct artery patency were studied in 14 patients with acute myocardial infarction. Lp(a) was measured by enzyme-linked immunosorbent assay and the timing of reperfusion was evaluated using the creatine kinase myosin-brain fraction and myoglobin release curves. Thrombolysis in Myocardial Infarction (TIMI) flow grade and severity of coronary artery disease were assessed using a scoring system based on coronary angiography performed during hospitalization and 6 months thereafter. The median Lp(a) level on admission was 127 (range 11–2 513) mg/l. The overall coronary score was higher in patients with Lp(a) levels greater than 127 mg/l than in those with Lp(a) less than 127 mg/l (P < 0.01). Lp(a) level correlated with the coronary score measured during hospitalization (r = 0.80, P < 0.01) and 6 months later (r = 0.79, P < 0.01). The timing of reperfusion and infarct artery patency were not dependent on the serum Lp(a) level. The results show that the serum Lp(a) level is associated with the angiographic severity of coronary artery disease postmyocardial infarction but does not determine the patency of the infarct-related artery.

Atherosclerosis, type I collagen cross-linking and homocysteine

Patients with homocystinuria have several connective tissue manifestations, the most severe being atherosclerosis. Furthermore, elevated plasma homocysteine concentrations correlate with atherosclerosis without other features of homocystinuria [1]. Homocysteine has been shown to interfere with collagen cross-linking, although the exact biochemical mechanism is unclear [2]. Moreover, the serum level of carboxyterminal telopeptide of human type I collagen (ICTP), the degradation product of type I collagen, decreases in patients with homocystinuria [3]. Thus, the decreased tensile strength of the connective tissue may be at least partially responsible for the clinical manifestations of homocystinuria. We have recently shown that the ICTP assay detects only degradation of mature, trivalently cross-linked type I collagen [4]. We, therefore, wanted to study if there really is a negative correlation between serum homocysteine and ICTP concentrations in patients with severe coronary atherosclerosis. Serum samples were obtained from 109 consecutive patients (75 men, 34 women, mean age 6299) before coronary artery bypass grafting at the Oulu University Hospital. Forty-nine of the patients had previously suffered a myocardial infarction and 70 patients had three-vessel disease. The collection of the samples was approved by the local ethics committee. Homocysteine (reference range 4.5–12.4 mmol/l) and ICTP (reference range 1.6–4.6 mmol/l) were measured by commercially available methods (Abbott Laboratories and Orion Diagnostica, respectively). Spearman’s rank correlation was used for the correlation analyses. The mean ICTP and homocysteine concentrations were 3.391.3 and 14.494.8 mg/l, respectively. These correlated significantly with each other (r=0.260, P=0.006) (Fig. 1). However, both ICTP and homocysteine also correlated significantly with the age of the patients (r=0.265, P=0.005 and 0.310, P= 0.001, respectively). We did not find the expected negative correlation between serum ICTP and homocysteine concentrations, which suggests that cross-linking of type I collagen does not decrease in the presence of increasing homocysteine concentrations, although the observed homocysteine levels were not very high in the present series. Both ICTP and homocysteine correlated significantly with age. Atherosclerosis, in addition to aging, possibly accelerates the turnover of type I collagen, which may mask the effect of homocysteine on collagen cross-linking. Type I collagen is the major constituent of mineralised bone, and thus part of the circulating ICTP could be derived from bone turnover via the matrix metalloproteinase (MMP) pathway [4]. Measurements of type III collagen metabolism with respect to, for instance, plaque rupture might be more relevant, since type III collagen is very abundant in atherosclerotic plaques and vessel walls [5], being absent in bone.