Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study

BACKGROUND The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. METHODS AND RESULTS The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality. CONCLUSIONS We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

Chronic converting enzyme inhibition normalizes QT interval in aging rats

The aim of the present study was to investigate the effects of converting enzyme inhibition by captopril on ECG parameters in aged rats. Four-month-old male rats received captopril dissolved in tap water (0.5 mg/l) or tap water for 2 or 20 months. At the end of treatment, under anesthesia, RR and PR interval, P wave and QRS duration, QT and corrected QT interval were measured in all animals. On the following day, chronic ECG (lead II) recordings were performed to quantify supraventricular (SVPB) or ventricular premature beats (VPB). After sacrifice, the hearts were removed and weighed. RR interval was similar in young and untreated aged rats, but significantly larger in aged rats treated with captopril. P wave and QRS length did not differ among groups. PR interval was significantly larger in old than in young rats and was not affected by captopril. Corrected QT interval was larger in aged than in young rats (117 ± 4 vs 64 ± 6 ms, P<0.05) and was reduced by captopril (71 ± 6 ms, P<0.05). VPB were absent in young rats and highly frequent in untreated old animals (8.4 ± 3.0/30 min). Captopril significantly reduced VPB in old rats (0.3 ± 0.1/30 min, P<0.05). The cardiac hypertrophy found in untreated aged rats was prevented by captopril (3.44 ± 0.14 vs 3.07 ± 0.10 mg/g, P<0.05). The beneficial effects of angiotensin converting enzyme inhibition on the rat heart during the aging process are remarkable.

Characterization of the electrocardiographic pattern of individuals with cerebral palsy

Background: Dentists of Lar Sao Francisco observed during dental treatment that children with cerebral palsy (CP) had increased heart rate (HR) and lower production of saliva. Despite the high prevalence of CP found in the literature (2.08-3.6/1000 individuals), little is known about the electrocardiographic (ECG) characteristics, especially HR, of individuals with CP. Objective: This study aimed to investigate the hypothesis that individuals with CP have a higher HR and to define other ECG characteristics of this population. Methods: Ninety children with CP underwent clinical examination and 12-lead rest ECG. Electrocardiographic data on rhythm, HR, PR interval, QRS duration, P/QRS/T axis, and QT, QTc and T(peak-end) intervals (minimum, mean, maximum, and dispersion) were measured and analyzed then compared with data from a control group with 35 normal children. Fisher and Mann-Whitney U tests were used, respectively, to compare categorical and continuous data. Results: Groups cerebral palsy and control did not significantly differ in age (9 +/- 3 x 9 +/- 4 years) and male gender (65% x 49%). Children with CP had a higher HR (104.0 +/- 20.6 x 84.2 +/- 13.3 beats per minute; P < .0001), shorter PR interval (128.8 +/- 15.0 x 138.1 +/- 15.1 milliseconds; P = .0018), shorter QRS duration (77.4 +/- 8.6 x 82.0 +/- 8.7 milliseconds; P = .0180), QRS axis (46.0 degrees +/- 26.3 degrees x 59.7 degrees +/- 24.8 degrees; P = .0024) and T-wave axis (34.3 degrees +/- 28.9 degrees x 42.9 degrees +/- 17.1 degrees; P = .034) more horizontally positioned, and greater mean QTc (418.1 +/- 18.4 x 408.5 +/- 19.4 milliseconds; P = .0110). All the electrocardiogram variables were within the reference range for the age group including those with significant differences. Conclusion: Children with CP showed increased HR and other abnormal ECG findings in the setting of this investigation. Further studies are needed to explain our findings and to correlate the increased HR with situations such as dehydration, stress, and autonomic nervous disorders. (C) 2011 Elsevier Inc. All rights reserved.

STANDARDIZATION OF SOME ELECTROCARDIOGRAPHIC PARAMETERS OF CAPTIVE LEOPARD CATS (LEOPARDUS TIGRINUS)

Thirty-three captive leopard cats, Leopardus tigrinus, were anesthetized with xylazine (1-2 mg/kg) and ketamine (10 mg/kg), and electrocardiograph (ECG) tests were recorded in all leads with 1 cm = 1 mV sensibility and 25 mm/sec speed repeating DII lead at 50 mm/sec speed with the same sensibility. Results expressed by mean and standard deviation were: heart rate (HR) = 107 +/- 17 (bpm); P-wave = 0.048 +/- 0.072 (s) x 0.128 +/- 0.048 (mV); PR interval = 0.101 +/- 0.081 (s); QRS compound = 0.053 +/- 0.012 (s) x 1.446 +/- 0.602 (mV); QT interval = 0.231 +/- 0.028 (s); R-wave (CV(6)LL) = 1.574 +/- 0.527 (mV); R-wave (CV(6)LU) = 1.583 +/- 0.818 (mV); heart rhythm: normal sinus rhythm (15.2%), sinus rhythm with wandering pacemaker (WPM) (60.6%), sinus arrhythmia with WPM (24.2%); electric axis: between +30 degrees and +60 degrees (6.1%), +60 (6.1%), between +60 degrees and +90 degrees (57.6%), +90 degrees (9%), between +90 degrees and +120 degrees (21.2%); ST segment: normal (75.7%), elevation (18.2%), depression (6.1%); T-wave polarity (DII): positive (100%); T-wave (V(10)): absent (6.1%), negative (63.6%), positive (18.2%), and with interference (12.1%). Through ECG data comparison with other species, unique features of Leopardus tigrinus` (leopard cat) ECG parameters were detected. Some of the study animals presented with an R-Wave amplitude that was indicative of left ventricle overload according to patterns for normal domestic cats (Felis cati). Echocardiographic exams revealed normal heart cavities` function and morphology. The aim of this study was to establish some electrocardiographic parameters of captive L. tigrinus.

PREDICTIVE FACTORS FOR THE PROGRESSION OF CHRONIC CHAGAS CARDIOMYOPATHY IN PATIENTS WITHOUT LEFT VENTRICULAR DYSFUNCTION

The identification of predictors for the progression of chronic Chagas cardiomyopathy (CCC) is essential to ensure adequate patient management. This study looked into a non-concurrent cohort of 165 CCC patients between 1985 and 2010 for independent predictors for CCC progression. The outcomes were worsening of the CCC scores and the onset of left ventricular dysfunction assessed by means of echo-Doppler cardiography. Patients were analyzed for social, demographic, epidemiologic, clinical and workup-related variables. A descriptive analysis was conducted, followed by survival curves based on univariate (Kaplan-Meier and Cox’s univariate model) and multivariate (Cox regression model) analysis. Patients were followed from two to 20 years (mean: 8.2). Their mean age was 44.8 years (20-77). Comparing both iterations of the study, in the second there was a statistically significant increase in the PR interval and in the QRS duration, despite a reduction in heart rates (Wilcoxon < 0.01). The predictors for CCC progression in the final regression model were male gender (HR = 2.81), Holter monitoring showing pauses equal to or greater than two seconds (HR = 3.02) increased cardiothoracic ratio (HR = 7.87) and time of use of digitalis (HR = 1.41). Patients with multiple predictive factors require stricter follow-up and treatment.

Effects of propranolol on the QT dispersion in congestive heart failure

OBJECTIVE - Studies have shown that therapy with beta-blockers reduces mortality in patients with heart failure. However, there are no studies describing the effects of propranolol on the QT dispersion in this population. The objective of this study was to assess the electrophysiological profile, mainly QT dispersion, of patients with heart failure regularly using propranolol. METHODS - Fifteen patients with heart failure and using propranolol were assessed over a period of 12 months. Twelve-lead electrocardiograms (ECG) were recorded prior to the onset of beta-blocker therapy and after 3 months of drug use. RESULTS - A significant reduction in heart rate, in QT dispersion and in QTc dispersion was observed, as was also an increase in the PR interval and in the QT interval, after the use of propranolol in an average dosage of 100 mg/day. CONCLUSION - Reduction in QT dispersion in patients with heart failure using propranolol may explain the reduction in the risk of sudden cardiac death with beta-blocker therapy, in this specific group of patients.

Pompe's disease or type IIa glycogenosis

This is the report of a five-month-old child presenting clinical evidence of Pompe's disease: severe hypotonicity, hyporeflexia and congestive heart failure. The ECG showed a short PR interval, the chest radiography disclosed marked cardiomegaly, and the echocardiogram revealed marked left ventricular hypertrophy - the most typical finding of this disease. A skeletal muscle biopsy led to final diagnosis, because in the histopathologic study marked increased glycogen accumulation was evident. Death occurred two months after symptom onset.

Characterization of the in vivo cardiac electrophysiologic effects of high-dose cocaine in closed-chest, anesthetized dogs with normal hearts

OBJECTIVE: To characterize the cardiac electrophysiologic effects of cocaine. METHODS: In 8 dogs (9-13 kg), electrophysiologic parameters and programmed stimulation were undertaken using transvenous catheters at baseline, and after cocaine intravenous infusion (12 mg/kg bolus followed by 0.22 mg/kg/min for 25 minutes). RESULTS: Cocaine plasma levels (n=5) rose to 6.73± 0.56 mg/mL. Cocaine did not affect sinus cycle length and arterial pressure. Cocaine prolonged P wave duration (54±6 vs 73±4 ms, P<0.001), PR interval (115±17 vs 164±15 ms, P<0.001), QRS duration (62±10 vs 88±14 ms, P<0.001), and QTc interval (344±28 vs 403±62 ms, P=0.03) but not JT interval (193±35 vs 226±53 ms, NS). Cocaine prolonged PA (9±6 vs 23±8 ms, P<0.001), AH (73±16 vs 92±15 ms; P=0.03), and HV (35±5 vs 45±3ms; P<0.001) intervals and Wenckebach point (247±26 vs 280±28 ms, P=0.04). An increase occurred in atrial (138±8 vs 184± 20 ms; P<0.001) and ventricular (160±15 vs 187±25 ms; P=0.03) refractoriness at a cycle length of 300 ms. Atrial arrhythmias were not induced in any dog. Ventricular fibrillation (VF) was induced in 2/8 dogs at baseline and 4/8 dogs after cocaine. CONCLUSION: High doses of cocaine exert significant class I effects and seem to enhance inducibility of VF but not of atrial arrhythmias.

Predictors of Arrhythmic Events Detected by Implantable Loop Recorders in Renal Transplant Candidates

AbstractBackground:The recording of arrhythmic events (AE) in renal transplant candidates (RTCs) undergoing dialysis is limited by conventional electrocardiography. However, continuous cardiac rhythm monitoring seems to be more appropriate due to automatic detection of arrhythmia, but this method has not been used.Objective:We aimed to investigate the incidence and predictors of AE in RTCs using an implantable loop recorder (ILR).Methods:A prospective observational study conducted from June 2009 to January 2011 included 100 consecutive ambulatory RTCs who underwent ILR and were followed-up for at least 1 year. Multivariate logistic regression was applied to define predictors of AE.Results:During a mean follow-up of 424 ± 127 days, AE could be detected in 98% of patients, and 92% had more than one type of arrhythmia, with most considered potentially not serious. Sustained atrial tachycardia and atrial fibrillation occurred in 7% and 13% of patients, respectively, and bradyarrhythmia and non-sustained or sustained ventricular tachycardia (VT) occurred in 25% and 57%, respectively. There were 18 deaths, of which 7 were sudden cardiac events: 3 bradyarrhythmias, 1 ventricular fibrillation, 1 myocardial infarction, and 2 undetermined. The presence of a long QTc (odds ratio [OR] = 7.28; 95% confidence interval [CI], 2.01–26.35; p = 0.002), and the duration of the PR interval (OR = 1.05; 95% CI, 1.02–1.08; p < 0.001) were independently associated with bradyarrhythmias. Left ventricular dilatation (LVD) was independently associated with non-sustained VT (OR = 2.83; 95% CI, 1.01–7.96; p = 0.041).Conclusions:In medium-term follow-up of RTCs, ILR helped detect a high incidence of AE, most of which did not have clinical relevance. The PR interval and presence of long QTc were predictive of bradyarrhythmias, whereas LVD was predictive of non-sustained VT.

mitoKATP channel activation in the postanoxic developing heart protects E-C coupling via NO-, ROS-, and PKC-dependent pathways.

Whereas previous studies have shown that opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel protects the adult heart against ischemia-reperfusion injury, it remains to be established whether this mechanism also operates in the developing heart. Isolated spontaneously beating hearts from 4-day-old chick embryos were subjected to 30 min of anoxia followed by 60 min of reoxygenation. The chrono-, dromo-, and inotropic disturbances, as well as alterations of the electromechanical delay (EMD), reflecting excitation-contraction (E-C) coupling, were investigated. Production of reactive oxygen species (ROS) in the ventricle was determined using the intracellular fluorescent probe 2',7'-dichlorofluorescin (DCFH). Effects of the specific mitoK(ATP) channel opener diazoxide (Diazo, 50 microM) or the blocker 5-hydroxydecanoate (5-HD, 500 microM), the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 microM), the antioxidant N-(2-mercaptopropionyl)glycine (MPG, 1 mM), and the PKC inhibitor chelerythrine (Chel, 5 microM) on oxidative stress and postanoxic functional recovery were determined. Under normoxia, the baseline parameters were not altered by any of these pharmacological agents, alone or in combination. During the first 20 min of postanoxic reoxygenation, Diazo doubled the peak of ROS production and, interestingly, accelerated recovery of ventricular EMD and the PR interval. Diazo-induced ROS production was suppressed by 5-HD, MPG, or L-NAME, but not by Chel. Protection of ventricular EMD by Diazo was abolished by 5-HD, MPG, L-NAME, or Chel, whereas protection of the PR interval was abolished by L-NAME exclusively. Thus pharmacological opening of the mitoK(ATP) channel selectively improves postanoxic recovery of cell-to-cell communication and ventricular E-C coupling. Although the NO-, ROS-, and PKC-dependent pathways also seem to be involved in this cardioprotection, their interrelation in the developing heart can differ markedly from that in the adult myocardium.

Ventricular but not atrial electro-mechanical delay of the embryonic heart is altered by anoxia-reoxygenation and improved by nitric oxide.

BACKGROUND/AIM: Excitation-contraction coupling is modulated by nitric oxide (NO) which otherwise has either beneficial or detrimental effects on myocardial function during hypoxia-reoxygenation. This work aimed at characterizing the variations of electromechanical delay (EMD) induced by anoxia-reoxygenation within the developing heart and determining whether atrial and ventricular EMD are modulated by NO to the same extent. METHODS: Hearts of 4 or 4.5-day-old chick embryos were excised and submitted in vitro to normoxia (45 min), anoxia (30 min) and reoxygenation (60 min). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout experiment. Anoxia-reoxygenation-induced chrono-, dromo-and inotropic disturbances and changes in EMD in atrium (EMDa) and ventricle (EMDv) were investigated in control hearts and in hearts exposed to 0.1, 1, 10, 50 and 100 microM of DETA-NONOate (a NO donating agent) or to 50 microM of L-NAME (a NOS inhibitor). RESULTS: Under normoxia, heart rate, PR interval, ventricular shortening velocity, EMDa and EMDv were similar in control, L-NAME-treated and DETA-NONOate-treated hearts. Under anoxia, cardiac activity became markedly erratic within less than 10 min in all groups. At the onset of reoxygenation, EMDv was increased by about 300% with respect to the preanoxic value while EMDa did not vary significatively. Compared to control conditions, L-NAME or DETA-NONOate had no influence on the negative chrono-, dromo- and inotropic effects induced by anoxia-reoxygenation. However, L-NAME prolonged EMDv during anoxia and delayed EMDv recovery during reoxygenation while 100 microM DETA-NONOate had the opposite effects. EMDa was neither affected by NOS inhibitor nor NO donor. At the end of reoxygenation, all the investigated parameters returned to their basal values. CONCLUSION: This work provides evidence that a NO-dependent pathway is involved in regulation of the ventricular excitation-contraction coupling in the anoxic-reoxygenated developing heart.

Pseudo-pacemaker syndrome in a young woman with first-degree atrio-ventricular block.

First-degree atrio-ventricular (AV) block is defined as a PR interval longer than 200 ms. If too long, it can become clinically relevant and may mimic a pacemaker syndrome. We report the case of a young woman with a long PR interval, probably congenital, with episodes of syncope and dizziness since childhood. Pseudo-pacemaker syndrome is rare and is a Class IIa recommendation for a pacemaker implantation. A dual-chamber pacemaker was implanted and short AV delay was programmed, with rapid clinical improvement.

Specific inhibition of HCN channels slows rhythm differently in atria, ventricle and outflow tract and stabilizes conduction in the anoxic-reoxygenated embryonic heart model.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in pacemaker cells very early during cardiogenesis. This work aimed at determining to what extent these channels are implicated in the electromechanical disturbances induced by a transient oxygen lack which may occur in utero. Spontaneously beating hearts or isolated ventricles and outflow tracts dissected from 4-day-old chick embryos were exposed to a selective inhibitor of HCN channels (ivabradine 0.1-10microM) to establish a dose-response relationship. The effects of ivabradine on electrocardiogram, excitation-contraction coupling and contractility of hearts submitted to anoxia (30min) and reoxygenation (60min) were also determined. The distribution of the predominant channel isoform, HCN4, was established in atria, ventricle and outflow tract by immunoblotting. Intrinsic beating rate of atria, ventricle and outflow tract was 164+/-22 (n=10), 78+/-24 (n=8) and 40+/-12bpm (n=23, mean+/-SD), respectively. In the whole heart, ivabradine (0.3microM) slowed the firing rate of atria by 16% and stabilized PR interval. These effects persisted throughout anoxia-reoxygenation, whereas the variations of QT duration, excitation-contraction coupling and contractility, as well as the types and duration of arrhythmias were not altered. Ivabradine (10microM) reduced the intrinsic rate of atria and isolated ventricle by 27% and 52%, respectively, whereas it abolished activity of the isolated outflow tract. Protein expression of HCN4 channels was higher in atria and ventricle than in the outflow tract. Thus, HCN channels are specifically distributed and control finely atrial, ventricular and outflow tract pacemakers as well as conduction in the embryonic heart under normoxia and throughout anoxia-reoxygenation.

Tracheal instillation of urban PM2.5 suspension promotes acute cardiac polarization changes in rats

The mechanisms by which PM2.5 increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM2.5 induces acute cardiac polarization alterations in healthy Wistar rats. PM2.5 samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 µg PM2.5 were administered by tracheal instillation. P wave duration decreased significantly at 20 µg (0.99 ± 0.06, 0.95 ± 0.06, and 0.96 ± 0.07; P < 0.001), and 50 µg (0.98 ± 0.06, 0.98 ± 0.07, and 0.96 ± 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 µg (0.99 ± 0.06, 0.98 ± 0.07, and 0.97 ± 0.08) and 50 µg (0.99 ± 0.05, 0.97 ± 0.0, and 0.95 ± 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 µg (P < 0.001). QRS interval duration decreased at 20 and 50 µg in relation to blank filter solution and 10 µg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 µg (0.94 ± 0.12, 0.88 ± 0.14, and 0.88 ± 0.11) and 50 µg (1.00 ± 0.13; 0.97 ± 0.11 and 0.98 ± 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 µg (P < 0.001). PM2.5 induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.