Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort.

OBJECTIVE: Decreased production of endothelial nitric oxide (NO) is associated with different cardiovascular pathology. We studied the association between the Glu298Asp polymorphism of the NO producing gene, endothelial nitric oxide synthase (eNOS), and hypertension, left ventricular mass (LVM) and carotid artery intima-media thickness (IMT) in a population-based cohort of hypertensive and control subjects. DESIGN: Cross-sectional case-control study. SETTING: District around Oulu University Hospital, Northern Finland. SUBJECTS AND METHODS: The study population consisted of 600 middle-aged hypertensive subjects (300 men and 300 women) and 600 controls (300 men and 300 women) living in the City of Oulu. The hypertensive subjects were randomly selected by age stratification from the Social Insurance Institute register for reimbursement of antihypertensive medication. For each hypertensive subject, an age- and sex-matched control was randomly selected from the national health register. The overall participation rate was 87.8%. In the present study a total of 1024 subjects were screened. Echocardiographic examinations were performed by a trained cardiologist and carotid ultrasonographic examinations by a trained radiologist. RESULTS: The genotype distributions and allele frequencies between the hypertensive and control subjects and the relationship between the Glu298Asp variant and blood pressure, LVM and carotid artery IMT were determined. No differences in genotype distribution or allele frequencies were found between the hypertensive and control groups (the frequency of the Asp allele 0.299 vs. 0.288, respectively). Also, we could not find any association between the eNOS genotype and the measured cardiovascular complications. CONCLUSIONS: The Glu298Asp variant of the eNOS gene does not seem to be a major risk factor for cardiovascular alterations in the general population.

Ear oximetry: a noninvasive method for detection of patent foramen ovale: a study comparing dye dilution method and oximetry with contrast transesophageal echocardiography.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) may play an important role as a risk factor for ischemic stroke and some other neurological conditions. There is a need for low-cost and noninvasive methods for the detection of PFO. This study evaluates the accuracy of two simple bedside tests, the dye dilution method and ear oximetry, in the detection of PFO. METHODS: Dye dilution curves and ear oximetry recordings with a noninvasive ear densitometer were obtained from consecutive cryptogenic stroke patients referred for contrast transesophageal echocardiography (TEE). All test results were blindly assessed for the presence of PFO. Sensitivity and specificity were calculated with TEE used as a reference method. kappa statistics were used to measure interrater agreement. RESULTS: Dye dilution curves were obtained from 67 patients. Dye dilution correctly diagnosed 35 of the 46 patients who had PFO in TEE and all the 21 patients without PFO. Thus, the sensitivity (95% CI) of the dye dilution method was 76% (61% to 87%) and its specificity 100% (84% to 100%). Ear oximetry was done on 83 patients. Oximetry correctly diagnosed 45 of the 53 patients who had PFO in TEE and all of the 30 patients without PFO. Thus, the sensitivity of ear oximetry was 85% (72% to 93%) and its specificity 100% (88% to 100%). The interrater agreement was excellent (kappa value 0.94 for dye dilution and 0.90 for oximetry). CONCLUSIONS: Dye dilution and oximetry are both sensitive and specific methods for the detection of PFO. Oximetry has the following primary advantages over the currently available diagnostic methods: it is noninvasive, safe, and inexpensive and causes no discomfort for the patient. We suggest that oximetry could be used as a first-line screening method for PFO in patients with cryptogenic stroke. Ear oximetry also has potential use in epidemiological studies.

Heart rate variability and progression of coronary atherosclerosis.

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.

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.

Neurohumoral responses to a single haemodialysis in chronic renal patients.

The effect of volume reduction on vasoactive substances and their role in estimating dry weight in haemodialysis patients was studied. Plasma atrial natriuretic peptide (ANP), catecholamines, antidiuretic hormone, renin activity and serum aldosterone were measured in 12 patients before and after bicarbonate haemodialysis. Haemodynamical changes were registered and cardiac function and diameter of the inferior vena cava were measured by echocardiography before and after dialysis. Plasma concentration of ANP was significantly reduced by haemodialysis from 209 +/- 51 to 69 +/- 13 pg mL(-1) (n = 12, P < 0.05), whereas concentrations of the other hormones were unchanged. The change in the concentration of ANP did not have significant correlation with weight reduction. The concentration of ANP correlated positively with the diameter of the inferior vena cava (r = 0.70, P < 0.05) after dialysis, but not before dialysis. The concentration of ANP before or after haemodialysis or its change during dialysis did not correlate with any other biochemical parameter. The results show that plasma ANP level is decreased after volume reduction in patients with chronic renal failure, whereas other hormonal systems are unresponsive. However, plasma concentration of ANP seems to have no role in estimating dry weight in chronic haemodialysis patients.

Variants of renin-angiotensin system genes and echocardiographic left ventricular mass.

AIMS: Variants of renin-angiotensin system genes are shown to be associated with cardiovascular pathology. The association between renin-angiotensin system genes and left ventricular mass was investigated in a population-based case-control study. METHODS AND RESULTS: The association between echocardiographic left ventricular mass and both insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the methionine-threonine variant at position 235 of the angiotensinogen gene was studied in a random cohort of 430 hypertensive and 426 control subjects. No differences in the adjusted left ventricular mass values between the different genotypes were seen among either the hypertensive or the control subjects, whether men or women, or in the subgroups of normotensive or physically active subjects. Gene variation had no statistically significant synergistic effect on left ventricular mass values. In control women, the deletion allele of the angiotensin-converting enzyme gene was associated with an increased risk of left ventricular hypertrophy. However, this finding was based on a small number of women with left ventricular hypertrophy and should be interpreted with caution. CONCLUSION: Variations in renin-angiotensin system genes had no major effect on left ventricular mass in this middle-aged population-based cohort of hypertensives and control subjects.

Gender difference in autonomic and hemodynamic reactions to abrupt coronary occlusion.

OBJECTIVES: We sought to determine whether there are gender-related differences in autonomic and hemodynamic responses to abrupt coronary occlusion. BACKGROUND: The risk of sudden death before hospital admission is higher in men with an acute myocardial infarction. The reasons for this gender-related difference are not well understood. Cardiovascular autonomic regulation modifies the outcome of acute coronary events, and there are gender differences in the autonomic regulation of heart rate (HR) in normal physiologic circumstances. METHODS: We analyzed the changes in HR, HR variability and blood pressure and the occurrence of ventricular ectopic beats during a 2-min coronary occlusion in 140 men and 65 women referred for single-vessel coronary angioplasty. The ranges of nonspecific responses were determined by analyzing a control group of 19 patients with no ischemia during a 2-min balloon inflation in a totally occluded coronary artery. RESULTS: Women more often had ST segment changes (p < 0.01) and chest pain (p < 0.05) during the occlusion. Significant bradycardia or increase in HR variability as a sign of vagal activation occurred more often in women than in men (31% vs. 13%, p < 0.01 and 25% vs. 11%, p < 0.05, respectively). Coronary occlusion also more often caused (28% vs. 11%, p < 0.01) a decrease in blood pressure in women. The most pronounced female preponderance was in the incidence of Bezold-Jarisch-type reaction (i.e., simultaneous bradycardia and decrease in blood pressure [16% vs. 0.7%, p < 0.0001]). Logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia identified female gender to be an independent predictor of bradycardic reactions (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.7, p < 0.01), hypotensive reactions (OR 2.6, 95% CI 1.1 to 6.0, p < 0.05) and Bezold-Jarisch-type response (OR 22.2, 95% CI 2.5 to 200, p < 0.01). Significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats emerged as having borderline significance (OR 0.4, CI 0.1 to 1.1, p = 0.07). CONCLUSIONS: Vagal activation is more common in women than in men during abrupt coronary occlusion and may have beneficial antiarrhythmic effects, modifying the outcome of acute coronary events.

Baroreflex sensitivity in drug-treated systemic hypertension.

Baroreflex sensitivity is impaired in patients with systemic hypertension. The persistence of abnormal baroreflex sensitivity despite adequate blood pressure control may be one of the reasons why the effect of antihypertensive therapy on coronary artery disease mortality has been less than expected on the basis of the achieved blood pressure levels.

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.

Fatal occlusion of the left coronary main stem by a fragment from the femoral artery: a previously unreported complication of cardiac catheterization.

A 59-year-old man with grade III angina pectoris and 80% stenosis of the left anterior descending coronary artery developed an acute total occlusion of the artery during percutaneous transluminal coronary angioplasty (PTCA). Attempts at recanalisation and resuscitation were ineffective, and the patient died. The medico-legal autopsy revealed obstruction of left main coronary artery by a ringshaped piece of arterial wall that had been torn out of the femoral artery at the punction site and driven around the tip of the catheter into the orifice of the left coronary artery, filling it. This kind of complication of PTCA has not been described previously.

Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

No evidence for ischemic preconditioning during repeated vessel occlusion in coronary angioplasty.

Coronary angioplasty has been the favoured model in studying ischemic preconditioning in humans, but results have remained controversial, possibly due to some artefacts related to coronary balloon angioplasty as an ischemia model. We examined this issue by monitoring the sequential metabolic, functional and neurohumoral changes during repeated vessel occlusion in coronary angioplasty performed in patients with chronic angina pectoris. Two groups of patients undergoing two successive balloon inflations of approximately 2 min duration were studied. These balloon inflations were preceded by a short inflation performed immediately after introduction of the balloon into the stenosis. The aim of this primary inflation was to establish adequate coronary blood flow with the deflated balloon in the stenosis and to guarantee that the subsequent two balloon inflations were truly comparable in time. Group I consisted of 23 patients, in whom the changes in the degree of angina, pulmonary capillary wedge pressure (PCWP), atrial natriuretic peptide (ANP) and circulating catecholamines during the procedure were studied. The sequential changes in myocardial metabolism were monitored in group II of nine patients by determining the lactate extraction ratios and femoroarterial coronary sinus (Fa-CS) differences in pH and pCO2 before and after each balloon inflation. In group I, PCWP and total catecholamines increased similarly during both balloon inflations, but ANP remained unchanged. In group II patients the lactate extraction ratios turned negative, the Fa-CS pH-differences increased and the pCO2-differences decreased during vessel occlusions, the changes being somewhat more prominent during the second balloon inflation. To study adaptation to ischemia, the group I patients were divided into two subgroups with and without signs of ischemic dysfunction during balloon inflations (PCWP increase > 5 mmHg and < 5 mmHg, respectively), and the group II patients were divided into two subgroups with and without metabolic ischemia (lactate-producers and non-producers). The ANP levels were constantly higher in the patients demonstrating ischemic dysfunction during balloon inflations, but catecholamine levels increased only after the second balloon inflation. The anginal pain experienced by the patients and the signs of metabolic ischemia were identical during both balloon inflations. We conclude that acute ischemic preconditioning does not occur in patients with repeated vessel occlusions of approximately 2 min duration. The patients without ischemia during the procedure had more critical stenoses and pre-existing collaterals. However, other protective mechanisms, such as chronic adaptation at the cellular level or recruitment of new collaterals, cannot be excluded.

Dispersion of the QT interval and autonomic modulation of heart rate in hypertensive men with and without left ventricular hypertrophy.

Left ventricular hypertrophy is an independent risk factor for sudden cardiac death in hypertension, but the mechanisms of electrical instability associated with hypertrophy are not well known. We studied dispersion of the QT interval, an index of inhomogeneity of repolarization, and heart rate variability, a measure of cardiac autonomic modulation, in a randomly selected population of 162 men with systemic hypertension and made comparisons between the patients with echocardiographic evidence of left ventricular hypertrophy (left ventricular mass index > or = 131 g/m2, n = 44) and those without hypertrophy (left ventricular mass index < 131 g/m2, n = 118). The heart rate-corrected QT dispersion (67 +/- 37 versus 53 +/- 21 milliseconds, P < .05) and QT apex dispersion (55 +/- 22 versus 44 +/- 16 milliseconds, P < .01) were significantly longer in the patients with left ventricular hypertrophy than in those without hypertrophy. Thirteen of the 44 patients (30%) with hypertrophy versus 7 of the 118 patients (6%) without hypertrophy had an abnormally long QT apex dispersion ( > 70 milliseconds) (P < .001). The time and frequency domain measures of heart rate variability did not differ significantly between the patient groups with and without left ventricular hypertrophy. The measures of heart rate variability were not related to QT dispersion or left ventricular mass index but had a negative correlation with blood pressure values (eg, r = -.30 between the low-frequency component of heart rate variability and systolic pressure, P < .001). Age, body mass index, antihypertensive medication, and the other demographic variables were similar between the groups, but the patients with left ventricular hypertrophy had higher systolic (P < .01) and diastolic (P < .01) pressures compared with the patients without hypertrophy. Left ventricular hypertrophy in hypertensive men is associated with inhomogeneity of the early phase of ventricular repolarization, favoring susceptibility to reentrant ventricular tachyarrhythmias. Abnormalities in cardiac autonomic function, which may trigger a spontaneous onset of arrhythmias, are related to elevated blood pressure but not specifically to left ventricular hypertrophy.

Sex-related differences in autonomic modulation of heart rate in middle-aged subjects.

BACKGROUND: Women have worse outcomes when they experience acute myocardial infarction (MI), but the reasons for this sex-related difference are not well understood. Because cardiovascular neural regulation plays an important role in cardiac mortality, we studied possible sex-related differences in the autonomic modulation of heart rate (HR) in middle-aged subjects without known heart disease. METHODS AND RESULTS: Baroreflex sensitivity (BRS) and HR variability were studied in randomly selected, age-matched populations of middle-aged women (n = 186; mean age, 50 +/- 6 years) and men (n = 188; mean age, 50 +/- 6 years) without hypertension, diabetes, or clinical or echocardiographic evidence of heart disease. BRS measured from the overshoot phase of the Valsalva maneuver was significantly lower in women (8.0 +/- 4.6 ms/mm Hg, n = 152) than in men (10.5 +/- 4.6 ms/mm Hg, n = 151) (P < .001), and the low-frequency component of HR variability measured from ECG recordings also was lower in women (P < .001), whereas the high-frequency component was higher in women than in men (P < .001). The ratio between the low-and high-frequency oscillations also was lower in the women (P < .001). The increase of HR and decrease of high-frequency component of HR variability in response to an upright posture were smaller in magnitude in women than in men (P < .01 for both). After adjustment for differences in the baseline-variables, such as blood pressure, HR, smoking, alcohol consumption, and psychosocial score, the sex-related differences in BRS and HR variability still remained significant (P < .001 for all). Women with estrogen replacement therapy (n = 46) had significantly higher BRS and total HR variance than the age-matched women without hormone treatment (P < .01 for both), and the BRS and HR variability of the women with estrogen therapy did not differ from those of the age-matched men. CONCLUSIONS: Baroreflex responsiveness is attenuated in middle-aged women compared with men, but the tonic vagal modulation of HR is augmented. Hormone replacement therapy appears to have favorable effects on the cardiovascular autonomic regulation in postmenopausal women.

Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations?

OBJECTIVE: To investigate the relation between Helicobacter pylori infection and coronary heart disease (CHD). DESIGN: A case-control study. SETTING: Northern Finland (about 650,000 inhabitants). PATIENTS: 116 patients with angiographically documented CHD and 116 controls matched for age and gender randomly recruited from the register of the Finnish Social Insurance Institute. MAIN OUTCOME MEASURES: The odds ratio (OR) estimates for the association of H pylori infection with CHD. RESULTS: 64% of the CHD patients and 53% of the controls were seropositive for H pylori; the OR adjusted for age and gender was 1.5 (95% confidence interval (CI) 0.9 to 2.5). An additional adjustment for the common risk factors of CHD, including lipid concentrations, in a logistic regression analysis produced an OR estimate of 1.1 (95% CI 0.6 to 2.1). Among the controls, those who were H pylori positive had significantly (P = 0.03) higher concentrations of serum triglycerides than those who were H pylori negative: the trend among the cases was similar, but non-significant. The concentrations of HDL cholesterol tended to be lower in those who were H pylori positive than in those who were H pylori negative, among both the cases and the controls. CONCLUSIONS: The impact of H pylori infection as an independent risk factor for CHD seems to be minor. On the other hand the results are consistent with the hypothesis that H pylori infection might modify the serum lipid concentrations in a way that could increase the risk of CHD.

Heart rate variability in systemic hypertension.

Low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-standing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain measures of HR variability were compared in randomly selected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 +/- 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normotensive ones (52 +/- 19 vs 59 +/- 20 mss; p <0.01), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p <0.001 for both). Hypertensive subjects also had blunted changes of the normalized low- and high-frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p <0.001 for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the patients with hypertension (beta--0.20, p=0.01) and in the normotensive subjects (beta--0.28, p=0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normotensive controls. These data show that long-standing hypertension results in reduced overall HR variability and blunted autonomic responses to a change in body posture. Altered autonomic modulation of HR in hypertension is mainly due to elevated blood pressure and obesity in males with long-standing hypertension as compared with normotensive subjects.

Abnormalities in beat-to-beat dynamics of heart rate before the spontaneous onset of life-threatening ventricular tachyarrhythmias in patients with prior myocardial infarction.

BACKGROUND: Beat-to-beat analysis of RR intervals can reveal patterns of heart-rate dynamics, which are not easily detected by summary measures of heart-rate variability. This study was designed to test the hypothesis that alterations in RR-interval dynamics occur before the spontaneous onset of ventricular tachyarrhythmias (VT). METHODS AND RESULTS: Ambulatory ECG recordings from 15 patients with prior myocardial infarction (MI) who had spontaneous episodes of sustained VT during the recording and VT inducible by programmed electrical stimulation (VT group) were analyzed by plotting each RR interval of a sinus beat as a function of the previous one (Poincaré plot). Poincaré plots were also generated for 30 post-MI patients who had no history of spontaneous VT events and no inducible VT (MI control subjects) and for 30 age-matched subjects without heart disease (normal control subjects). The MI control subjects and VT group were matched with respect to age and severity of underlying heart disease. All the healthy subjects and MI control subjects showed fan-shaped Poincaré plots characterized by an increased next-interval difference for long RR intervals relative to short ones. All the VT patients had abnormal plots: 9 with a complex pattern, 3 ball-shaped, and 3 torpedo-shaped. Quantitative analysis of the Poincare plots showed the SD of the long-term RR-interval variability (SD2) to be smaller in all VT patients (52+/-14 ms; range, 31 to 75 ms) than in MI control subjects (110+/-24 ms; range, 78 to 179 ms, P<.001) or the normal control subjects (123+/-38 ms, P<.001), but the SD of the instantaneous beat-to-beat variability (SD1) did not differ between the groups. The complex plots were caused by periods of alternating sinus intervals, resulting in an increased SD1/SD2 ratio in the VT group. This ratio increased during the 1-hour preceding the onset of 27 spontaneous VT episodes (0.43+/-0.20) compared with the 24-hour average ratio (0.33+/-0.19) (P<.01). CONCLUSIONS: Reduced long-term RR-interval variability, associated with episodes of beta-to-beat sinus alternans, is a highly specific sign of a propensity for spontaneous onset of VT, suggesting that abnormal beat-to-beat heart-rate dynamics may reflect a transient electrical instability favoring the onset of VT in patients conditioned by structurally abnormal hearts.