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M Kupari

Publications and source records attributed to M Kupari.

At least 19 recordsLinked to original sources
PubMed2006

Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure.

AIMS: To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure. METHODS AND RESULTS: This was a double-blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty-two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 microg/kg followed by a continuous infusion of 0.1-0.2 microg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7-9 days, and in CO was 12-13 days. Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855, maximal metabolite levels occurred at day 3. CONCLUSIONS: Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1-3 days after starting the infusion, effects were sustained for up to at least a week.

Atrial Natriuretic Factor↗
PubMed2005

Leakage of cardiac troponin I in aortic valve stenosis.

OBJECTIVE: Degeneration and death of cardiomyocytes contribute to the genesis of heart failure (HF) in aortic valve stenosis (AS). We studied whether the ongoing myocyte damage in AS can be detected from circulating cardiac troponin I (cTnI) concentrations. DESIGN AND SETTING: A cross-sectional cohort study in a university hospital. SUBJECTS AND METHODS: We examined 131 adult patients undergoing echocardiography and cardiac catheterization for isolated AS. Blood was sampled from the aortic root and, in a subset of 49 patients, also from the coronary sinus for the determination of cTnI using a sensitive immunoanalysis. RESULTS: Seventy-three patients (56%) had detectable aortic cTnI (> or =5 ng L(-1)) with 30 of them (23% of the total group) having cTnI above the reference limit in healthy subjects (>14 ng L(-1)). Patients with detectable cTnI had a higher prevalence of HF than those with undetectable cTnI (42% vs. 19%, P = 0.004). Plasma cTnI rose from the aorta to the coronary sinus by > or =5 ng L(-1) in 13 of 49 patients with AS (27%) versus in none of 12 control patients free of structural heart disease (P = 0.044). AS patients with transcardiac cTnI gradients > or =5 ng L(-1) had lower left ventricular (LV) ejection fractions than AS patients with gradients <5 ng L(-1) (mean +/- SD, 52 +/- 14% vs. 61 +/- 11%; P = 0.011). CONCLUSIONS: Detectable circulating cTnI is not uncommon in AS and shows a moderate association with the presence of HF. Leakage of cTnI into the coronary sinus associates with impairment of LV systolic function. Monitoring cTnI could provide a means to expose incipient clinical deterioration in AS.

Aged↗
PubMed2004

Diagnosing heart failure in aortic valve stenosis.

OBJECTIVE: In aortic valve stenosis (AS), heart failure (HF) omens a high risk of death and is an indication for prompt valve replacement. We studied whether its detection can be facilitated by measuring plasma N-terminal B-type natriuretic peptide (Nt-BNP) or by estimating pulmonary capillary wedge pressure (PCWP) using echocardiography. DESIGN AND SETTING: A cross-sectional cohort study in a university hospital. SUBJECTS AND METHODS: We studied 137 consecutive adult patients referred to our unit for invasive evaluation of isolated AS. All patients underwent cardiac catheterization, measurement of plasma Nt-BNP and estimation of PCWP by Doppler echocardiography of transmitral and pulmonary venous flow velocities. The final diagnosis of HF was based on the combined criteria of dyspnoea on ordinary effort and PCWP >14 mmHg at cardiac catheterization. The performance of Nt-BNP and the PCWP estimate in the detection of HF were studied using receiver operating characteristic (ROC) analysis. RESULTS: Totally 42 patients had HF. A cardiologist's clinical diagnosis of HF had high specificity (94%) but poor sensitivity (66%). With an optimized cut-off point, plasma Nt-BNP had moderate sensitivity (77%) and specificity (79%) for HF; the ROC area was 0.83. The echocardiographic PCWP estimate classified 90% of patients correctly as having normal or truly elevated (>14 mmHg) PCWP. Its sensitivity and specificity for the diagnosis of HF were 80 and 95% respectively; the ROC area was 0.88. With a cut-off point of 12 mmHg, the sensitivity of the PCWP estimate was 85% and specificity, 88%. CONCLUSION: The recognition of HF in patients with AS can be improved by estimating PCWP using Doppler echocardiography of transmitral and pulmonary venous flow velocities.

Adult↗
PubMed2001

Testing genetic susceptibility loci for alcoholic heart muscle disease.

BACKGROUND: Although many heavy alcohol users have subclinical alcoholic heart muscle disease, only a very few develop severe dilated cardiomyopathy. Therefore, and because cardiac abnormalities correlate only weakly with the duration or quantity of drinking, individual susceptibility differences may exist. In this work we examined whether common gene variants previously associated with cardiac hypertrophy or altered alcohol metabolism could modify the effects of alcohol on the heart. METHODS: We studied 700 middle-aged male victims of sudden death who underwent a medicolegal autopsy. In addition to routine postmortem examination, the weights and the cavity and wall dimensions of the left and right ventricle were measured. Coronary artery stenoses were determined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk factors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism and solid-phase minisequencing techniques: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166A/C, aldosterone synthase -344C/T, alcohol dehydrogenases 2 and 3, acetaldehyde dehydrogenase 2, and cytochrome P-450 2E1 DraI, PstI, RsaI, and MspI. RESULTS: The most consistent effects of alcohol (p < 0.05) were a higher total heart weight and a larger right ventricle size with increasing daily drinking. However, these and other effects of alcohol were statistically fully independent of the studied genotypes. CONCLUSIONS: The gene polymorphisms selected for and analyzed in our study are unlikely to modify the effects of alcohol on the heart. Other unknown factors determine the individual susceptibility to alcoholic heart muscle disease.

Adult↗
PubMed2001

Dose dependent but non-linear effects of alcohol on the left and right ventricle.

OBJECTIVE: To assess how left (LV) and right ventricular (RV) size, wall thickness, and mass depend on daily alcohol consumption. Among alcoholics, most common findings have been LV hypertrophy and mild systolic or diastolic dysfunction, accompanied occasionally by ventricular dilatation resembling dilated cardiomyopathy. Although it is commonly agreed that chronic heavy alcohol use is injurious to the heart, the dose-injury relation remains a matter of dispute. DESIGN: Prospective series of 700 Finnish men aged 33-70 years who died out of hospital and underwent a medicolegal necropsy. METHODS AND RESULTS: Data on alcohol use and other risk factors were obtained from the spouse. At necropsy, a transversal slice of the heart was traced on a transparent sheet and analysed later for LV and RV cavity areas and wall thicknesses. Coronary artery stenoses were measured from silicone casts of the arteries. In analyses of all men, daily alcohol dose predicted heart weight (beta = 0.17, p < 0.001) and RV cavity area (beta = 0.14, p = 0.007) independent of body size, age, coronary artery disease, hypertension, diabetes, and smoking. In the subgroup of men free of significant coronary artery disease, LV area averaged (SEM) 11.0 (1.0) cm(2) in men drinking < 12 g/day, 7.7 (0.7) cm(2) in those drinking 72-180 g/day, and 10.0 (0.9) cm(2) in those drinking > 180 g/day (p = 0.054). Very heavy drinking (> 180 g/day) was associated with an increase in RV cavity area (p = 0.005). CONCLUSIONS: The effects of alcohol on the heart in middle aged men are dose dependent but partly non-linear. In the absence of coronary artery disease, LV size shows a U shaped reduction with increasing daily alcohol use accompanied by an increase in RV size with very heavy drinking. These findings question the idea of progressive LV dilatation with increasing alcohol consumption among male victims of sudden death.

Adult↗
PubMed2001

Coronary artery disease modifies left ventricular remodelling due to heavy alcohol consumption.

BACKGROUND: Coronary artery disease (CAD) and excessive alcohol use can both damage the myocardium. Their combined effect on the heart muscle has not been characterized. We set out to assess whether the presence of CAD modifies the effects of chronic alcohol consumption on the left ventricular (LV) structure in middle-aged men. METHODS: A postmortem examination was performed on 700 Finnish men (age range, 33-70 years) who experienced a sudden, nonhospital death. A coronary arteriography and measurement of the LV wall thickness, cavity area, and ratio by planimetry of transversal ventricular slices were done at the autopsy. The men were grouped by the most severe coronary artery diameter stenosis (<30%, 30-60%, >60%) and by daily alcohol dose (<12 g, 12-72 g, 72-180 g, >180 g) estimated by a structured interview of their lifetime partner. RESULTS: Analysis by ANCOVA, adjusted for age, body size, smoking, hypertension, and diabetes, showed a statistically significant interaction between the effects of coronary artery stenosis and daily alcohol dose on the LV cavity area (p = 0.037) and on the LV wall thickness/cavity area ratio (p = 0.018). In the group with <30% stenosis, the LV wall thickness/cavity area ratio (mean +/- SEM) increased from 1.6 +/- 0.2 mm/cm2 in men drinking <12 g/day to 6.2 +/- 1.4 mm/cm2 in men drinking 72-180 g/day (p = 0.021). A similar trend was seen in men with 30-60% coronary stenosis (p = 0.32). By contrast, in men with >60% coronary stenosis, the LV wall thickness/cavity area ratio decreased with increasing daily alcohol use from 2.2 +/- 0.3 to 1.4 +/- 0.1 mm/cm2 (p = 0.27). CONCLUSIONS: CAD modulates the effects of alcohol on the heart muscle. Heavy drinking results in concentric LV remodelling in men with no or only mild coronary artery stenoses whereas an opposite trend is seen in men with severe coronary artery obstructions. The mechanism of the interaction remains unknown.

Adult↗
PubMed2000

Baroreflex sensitivity and variants of the renin angiotensin system genes.

OBJECTIVES: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS: In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS: Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.

Adult↗
PubMed1999

Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction.

BACKGROUND: The -344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI. METHODS AND RESULTS: We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men. There was a nonsignificant trend of increasing risk of MI with number of copies of the -344C allele. However, this allele was associated in a gene dosage-dependent manner with markedly increased MI risk conferred by classic risk factors. Whereas smoking conferred a relative risk of MI of 2.50 (P=0.0001) compared with nonsmokers in the entire study population, the relative risk increased to 4.67 in -344CC homozygous smokers (relative to nonsmokers with the same genotype, P=0.003) and decreased to 1.09 in -344TT homozygotes relative to nonsmokers with this genotype. Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors. CONCLUSIONS: Smoking and dyslipidemia are more potent risk factors for nonfatal MI in males who have the -344C allele of CYP11B2.

Adult↗
PubMed1998

Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function.

BACKGROUND: Aldosterone has direct and indirect effects on the heart, and genetic variations in aldosterone synthesis could therefore influence cardiac structure and function. Such variations might be associated with polymorphisms in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalyzing the last steps of aldosterone biosynthesis. METHODS AND RESULTS: A Finnish population sample of 84 persons (44 women) aged 36 to 37 years was studied by M-mode and Doppler echocardiography to assess left ventricular size, mass, and function. Subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promoter) and the other in the second intron. In multiple regression analyses, the CYP11B2 promoter genotype predicted statistically significant variations in left ventricular end-diastolic diameter (beta=.40, P<.0001), end-systolic diameter (beta=.33, P=.0009), and mass (beta=.17, P=.023). These effects were independent of potentially confounding factors, including sex, body size, blood pressure, physical activity, smoking, and ethanol consumption. Genotype groups also differed in a measure of left ventricular diastolic function, the heart rate-adjusted atrial filling fraction (P=.018). Increased dietary salt, which is known to predict increased left ventricular mass, had this effect only in association with certain CYP11B2 genotypes (P<.001). CONCLUSIONS: Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults free of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.

Adult↗
PubMed1998

Free fatty acid kinetics and oxidation in congestive heart failure.

To characterize fuel utilization of patients with congestive heart failure (CHF), we measured serum free fatty acid (FFA), counterregulatory hormone concentrations, whole body substrate oxidation rates (indirect calorimetry), and the turnover and oxidation rates of FFA ([1-(14)C]-palmitate infusion) in 7 patients with CHF and in 7 cardiac patients without CHF after an overnight fast. Plasma glucose and serum insulin concentrations were comparable, whereas serum FFA, blood ketone body, and fasting blood lactate (p <0.05 for all) concentrations were significantly increased in patients with CHF compared to those without CHF. Fasting plasma norepinephrine (p <0.05), serum cortisol (p <0.01), and growth hormone (p <0.01) concentrations were also higher in patients with CHF than in those without CHF. Rates of energy expenditure at rest (62 +/- 2 vs 56 +/- 1 J x kg(-1) x min(-1), p <0.05), FFA turnover (6.5 +/- 0.5 vs 5.0 +/- 0.4 micromol x kg(-1) x min(-1), p <0.05), and oxidation (2.0 +/- 0.2 vs 1.5 +/- 0.1 micromol x kg(-1) x min(-1)], p <0.05) were significantly higher in patients with CHF than in control subjects. In univariate analysis, the left ventricular ejection fraction was inversely correlated and the plasma norepinephrine concentration positively correlated with both energy expenditure at rest, FFA turnover, and the FFA oxidation rate. In multivariate analysis, the plasma norepinephrine concentration was the most significant predictor of increased FFA oxidation rate. We conclude that release of FFAs to the circulation and their subsequent oxidation are increased in patients with severe CHF after an overnight fast. These changes might reflect stress hormone-induced lipolysis and accompanying stimulation of serum FFA oxidation via mass action.

Aged↗
PubMed1998

Alcohol, cardiac arrhythmias and sudden death.

Studies in experimental animals have shown varying and apparently opposite effects of alcohol on cardiac rhythm and conduction. Given acutely to non-alcoholic animals, ethanol may even have anti-arrhythmic properties whereas chronic administration clearly increases the animals' susceptibility to cardiac arrhythmias. Chronic heavy alcohol use has been incriminated in the genesis of cardiac arrhythmias in humans. The evidence has come from clinical observations, retrospective case-control studies, controlled studies of consecutive admissions for arrhythmias, and prospective epidemiological investigations. Furthermore, electrophysiological studies have shown that acute alcohol administration facilitates the induction of tachyarrhythmias in selected heavy drinkers. The role of alcohol appears particularly conspicuous in idiopathic atrial fibrillation. Occasionally, ventricular tachyarrhythmias have also been provoked by alcohol intake. Several lines of evidence suggest that heavy drinking increases the risk of sudden cardiac death with fatal arrhythmia as the most likely mechanism. According to epidemiological studies this effect appears most prominent in middle-aged men and is only partly explained by confounding traits such as smoking and social class. The basic arrhythmogenic effects of alcohol are still insufficiently delineated. Subclinical heart muscle injury from chronic heavy use may be instrumental in producing patchy delays in conduction. The hyperadrenergic state of drinking and withdrawal may also contribute, as may electrolyte abnormalities, impaired vagal heart rate control, repolarization abnormalities with prolonged QT intervals and worsening of myocardial ischaemia or sleep apnoea. Most of what we know about alcohol and arrhythmias relates to heavy drinking. The effect of social drinking on clinical arrhythmias in non-alcoholic cardiac patients needs to be addressed further.

Alcohol Drinking↗
PubMed1998

Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males.

OBJECTIVES: Two diallelic polymorphisms, one in the transcriptional regulatory region (promoter) and the other in the second intron, have been identified in the aldosterone synthase (CYP11B2) gene encoding aldosterone synthase, the enzyme catalysing the last steps of aldosterone biosynthesis. We have examined the associations between these genetic variations and adrenocortical function in a cohort of Finnish males. DESIGN: A cross-sectional study. SETTING: Helsinki University Central Hospital, Finland. SUBJECTS: Ninety-two males aged 30-55 years. MAIN OUTCOME MEASURES: Basal adrenocortical function was assessed by measuring urinary excretion of aldosterone and cortisol. Functional activity was determined by responses of several adrenal steroids to dexamethasone suppression followed by ACTH stimulation. Polymerase chain reactions were used to identify the polymorphisms in the CYP11B2 gene. RESULTS: The -344TT genotype group in the CYP11B2 promoter had lower systolic blood pressures (P=0.039), but higher urinary aldosterone excretion (P=0.016), and 11-deoxycortisol responses to ACTH stimulation (P=0.021) than the-344CC genotype group. Urinary aldosterone excretion (P=0.033), 11-deoxycortisol (P=0.026), and aldosterone (P=0.013) responses to ACTH were higher in the intron 2 conversion than the nonconversion genotype groups. CONCLUSIONS: Polymorphisms in or near the aldosterone synthase gene are associated with variations in aldosterone and 11-deoxycortisol production in males. This may modulate the activity of the renin-angiotensin system and thereby contribute to blood pressure regulation.

Adrenal Cortex↗
PubMed1997

Effects of acute alcohol ingestion on heart rate variability in patients with documented coronary artery disease and stable angina pectoris.

The effects of acute alcohol intake (ethanol blood concentration 1.3 +/- 0.4%) on heart rate variability were evaluated with 24-hour Holter recordings in 20 patients with stable coronary artery disease in a juice-controlled experiment. In the frequency domain analysis, the high-, low-, and very low frequency components were significantly decreased after alcohol: these changes last longer than the elimination of alcohol.

Adult↗
PubMed1997

Heart failure ketosis.

OBJECTIVE: To assess whether blood ketone bodies are increased in congestive heart failure (CHF). METHODS: Thirteen patients with CHF and 11 cardiac patients without CHF took part in the study. Blood acetoacetate and b-hydroxybutyrate levels and the pertinent metabolic and hormonal milieu were measured during 20 h fast and after 2 h glucose infusion. RESULTS: The averaged blood ketone body and free fatty acid levels were significantly higher during the fast and also remained higher after glucose infusion in patients with CHF than in the control group. The areas under ketone body concentration time curve over the last 8 h of the fast were 3522 +/- 662 mumol L-1 h-1 (SE) and 1789 +/- 192 mumol L-1 h-1 in patients with and without CHF, respectively (P = 0.022). Circulating noradrenaline and growth hormone were higher but glucagon lower in patients with CHF than in the controls (P < 0.05 for all differences) whereas the glucose and insulin concentrations were comparable in the study groups. At the time of peak ketonaemia the glucagon-to-insulin ratio was lower in patients with CHF than in patients without CHF (P = 0.04). CONCLUSIONS: These data suggest that severe CHF is a ketosis-prone state. Augmented supply of free fatty acids for ketogenesis due to increased stress hormone-related lipolysis is one likely mechanism.

3-Hydroxybutyric Acid↗