Prolonged PR intervals are associated with epicardial adipose tissue and recurrence after catheter ablation in persistent atrial fibrillation.

Epicardial adipose tissue (EAT) has been reported to promote myocardial fibrosis and to affect intracardiac conduction. The PR interval reflects the conduction from the atria to the Purkinje fibers and may be associated with the EAT volume, especially in persistent atrial fibrillation (AF) patients. We aimed to investigate the relationship between the EAT and PR interval in patients with persistent AF. We enrolled 268 persistent AF patients who underwent catheter ablation (CA) and divided the patients into two groups: the normal PR interval group (PR interval less than 200 ms: Group N) and long PR interval group (PR interval 200 ms or more: Group L). We then analyzed the association between the total EAT volume around the heart and PR interval and calculated the ratio of the duration of the P wave (PWD) to the PR interval (PWD/PR interval). Moreover, we investigated whether a long PR interval was associated with the outcomes after ablation. The total EAT volume was significantly larger in Group L than Group N (Group N: 131.4 ± 51.8 ml vs. Group L: 151.3 ± 63.3 ml, p = 0.039). A positive correlation was also observed between the PWD/PR interval and EAT volume in Group L (r = 0.345, p = 0.039). A multivariate analysis also revealed that a long PR interval was independently associated with AF recurrence after CA (hazard ratio [HR] 2.071, p = 0.032). The total EAT volume was associated with a long PR interval, and a long PR interval was a significant risk factor for recurrence after ablation in persistent AF patients.

Effect of Maternal Ursodeoxycholic Acid Treatment on Fetal Atrioventricular Conduction in Patients with Intrahepatic Cholestasis of Pregnancy.

INTRODUCTION: The aim of this study was, first, to investigate the difference in fetal atrioventricular conduction in patients with and without intrahepatic cholestasis of pregnancy (ICP) by measuring the fetal PR interval; second, to evaluate the altering effect of ursodeoxycholic acid (UDCA) treatment on the fetal PR interval in ICP patients. METHODS: The study consisted of 42 ICP patients and 48 healthy pregnant women. Fetal echocardiography was performed to measure the mechanical PR interval. The fetal PR interval and the clinical characteristics were compared between the two groups. The effect of UDCA treatment on the fetal PR interval in ICP patients was evaluated. RESULTS: In ICP patients, significantly longer fetal PR intervals were observed than in the control group (123.21 ± 8.54 vs. 115.13 ± 5.95 ms, p < 0.001). In the ICP group, there was a positive correlation between the fetal PR interval and maternal fasting total bile acid (TBA) levels (r = 0.514, p = 0.001). After 1 week of treatment with UDCA in patients with ICP, the PR interval was shorter than before, although the reduction was not statistically significant (120.98 ± 6.70 vs. 123.21 ± 8.54 ms, p = 0.095). In patients with severe ICP (TBA >40 mmol/L, n = 10), a significant reduction in the fetal PR interval was observed after treatment with UDCA (127.5 ms [IQR, 118.0-134.75] before vs. 122 ms [IQR, 109.5-126.5] after, p = 0.037). CONCLUSION: Fetal PR interval increased in ICP patients in correlation with maternal serum TBA concentration. Treatment with UDCA may have limited positive effects on the fetal AV conduction system. The beneficial effects of UDCA on the fetal PR interval may be more pronounced in patients with higher bile acid levels.

Incidence, clinical characteristics, electrophysiological characteristics and outcomes of patients with baseline PR prolongation undergoing radiofrequency ablation for Atrioventricular nodal reentrant tachycardia.

AIMS AND OBJECTIVES: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia (SVT). Prolonged PR interval(>200 ms) on baseline electrocardiogram (ECG) is uncommon in such patients. The aim of the current study was to evaluate the incidence, clinical, electrophysiological characteristics, and outcomes of patients with baseline prolongation of PR interval undergoing radio-frequency ablation (RFA) for AVNRT. METHODS: Over 10 years, out of the total number of 1435 patients with diagnosed AVNRT, 16 patients had prolonged PR intervals at baseline. All underwent elective RFA. A retrospective analysis of clinical, and electrophysiological characteristics and outcomes was done. The PR interval and atria-ventricular block cycle length values were compared with those patients with a normal interval at baseline and had undergone a successful slow pathway modification for AVNRT. RESULTS: Out of 1435 patients with AVNRT, 16 (0.9 %) patients had baseline PR prolongation on ECG. The mean(+SD) age of the study population was 62.9 + 15.9 years. 10 (62.5 %) were males. The average PR interval was 264.2 + 24.1 ms. Slow fast AVNRT was seen in all. The anatomical site of success for ablation was the lower part of Koch's triangle in all patients. During ablation, a good sustained junctional rhythm was noted in all, with no AV (Atrioventricular) block or PR prolongation noted during ablation in any of the patients. PR interval decreased by more than 20 ms in 10 (62.5 %) patients. AVBCL (AV node block cycle length) increased on an average of 58.7 ms post-ablation. Only one patient developed AV block on follow-up. CONCLUSION: A prolonged PR interval on baseline ECG is uncommon in patients with AVNRT. In these patients, slow pathway modification can be done safely and effectively. AVBCL (AV node block cycle length) increases immediately post-ablation. The risk of AV block though low persists on follow-up.

Post-transcatheter aortic valve implantation isolated PR prolongation: incidence and clinical significance.

AIMS: Conduction abnormalities post-transcatheter aortic valve implantation (TAVI) are common. Post-TAVI PR prolongation was mainly studied as an adjunct to new-onset bundle branch block. The net effect of isolated PR prolongation (IPRP) without post-TAVI QRS changes is not well known. The aim of this study was to define the incidence and clinical significance of post-TAVI IPRP. METHODS AND RESULTS: A total of 1108 consecutive TAVI patients were reviewed. Patients with IPRP were compared with patients without post-TAVI electrocardiogram (ECG) changes. Clinical outcomes included permanent pacemaker implantation (PPI) and overall mortality. A total of 146 patients with IPRP were compared with 290 patients without post-TAVI ECG changes. At 1 year follow-up, 4 (2.7%) and 7 (2.4%) patients underwent PPI (P = 0.838) and 10 (6.8%) and 25 (8.6%) died (P = 0.521), from the study and control groups, respectively. No patient with IPRP and narrow QRS underwent PPI during 1 year post-TAVI, and all death events were non-cardiac except one unknown cause. Permanent pacemaker implantation rates among patients with IPRP and wide QRS were higher (n = 4, 12.1%), compared with patients with wide QRS without post-TAVI ECG change (n = 3, 4%) however not reaching statistical significance (P = 0.126). Multivariate Cox proportional hazards model demonstrated that in patients with narrow QRS, neither PR prolongation nor baseline or maximal PR intervals was associated with the combined endpoint of PPI and mortality. However, in patients with wide QRS, baseline PR intervals and QRS width, but not PR prolongation were associated with the combined outcome. CONCLUSION: Post-TAVI IPRP in patients with narrow QRS is not associated with adverse outcome. This finding may translate clinically into a more permissive approach to these patients.

Association of preoperative electrocardiographic markers with sepsis in elderly patients after general surgery.

BACKGROUND: Electrocardiographic markers, as surrogates for sympathetic excitotoxicity, are widely predictive of cardiovascular adverse events, but whether these markers can predict postsurgical sepsis (SS) is unclear. METHODS: We retrospectively analyzed patients who underwent abdominal surgery from March 2013 to May 2023. We collected basic data, comorbidities, blood samples, echocardiology, electrocardiogram, and surgical data, as well as short-term outcome. The primary endpoints were postsurgical SS, in which logistic regression analyses can identify independent risk factors. The optimal cut-off value predictive postsurgical SS both P wave and PR interval were calculated in the receiver operating characteristic curve (ROC). RESULTS: A total of 1988 subjects were analyzed, and the incidence of postsurgical SS was 3.8%. The mean age at enrollment was 68.6 ± 7.1 years, and 53.2% of the participants were men. In the ROC analysis, the areas under the curve (AUC) for P wave and PR interval predictive postsurgical SS were 0.615 (95%CI, 0.548-0.683; p = 0.001) and 0.618 (95%CI, 0.554-0.682; p = 0.001), respectively. The P wave and PR interval predicted postoperative sepsis with optimal discrimination of 103 and 157 ms, with a sensitivity of 0.744 and 0.419, and a specificity of 0.427 and 0.760. P-wave less than 103 ms or PR interval less than 157 ms associated with a 2.06 or 2.33 fold increase occurred risk postsurgical SS. CONCLUSIONS: Shorter P-wave and PR intervals were both independently associated with postsurgical SS. These preoperative electrophysiological markers could have potential useful for early recognition of postoperative SS.

Value of frontal QRS axis for risk stratification of individuals with prolonged PR interval.

BACKGROUND: There is ongoing controversy regarding the prognostic value of PR prolongation among individuals free of cardiovascular diseases. It is necessary to risk-stratify this population according to other electrocardiographic parameters. METHODS: This study is based on the Third National Health and Nutrition Examination Survey. Cox proportional hazard models were constructed and Kaplan-Meier method was used. RESULTS: A total of 6188 participants (58.1 ± 13.1 years; 55% women) were included. The median frontal QRS axis of the entire study population was 37° (IQR: 11-60°). PR prolongation was present in 7.6% of the participants, of whom 61.2% had QRS axis ≤37°. In a multivariable-adjusted model, mortality risk was highest in the group with concomitant prolonged PR interval and QRS axis ≤37° (hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.04-1.39). In models with similar adjustment where population were reclassified depending on PR prolongation and QRS axis, prolonged PR interval and QRS axis ≤37° was still associated with increased risk of mortality (HR: 1.18; 95% CI: 1.03-1.36) compared with normal PR interval. CONCLUSIONS: QRS axis is an important factor for risk stratification in population with PR prolongation. The extent to which this population with PR prolongation and QRS axis ≤37° is at higher risk of death compared with the population without PR prolongation.

Fetal cardiac dysfunction in pregnancies affected by intrahepatic cholestasis of pregnancy: A cohort study.

AIM: To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis. METHODS: This prospective cohort study included 49 pregnant participants with ICP at diagnosis and 49 nonaffected controls from a single public hospital. ICP was diagnosed based on clinical symptoms after excluding other causes of pruritus and presence of autoimmune diseases. Total bile acids were not obtained in this cohort. ICP pregnancies were assessed with a functional echocardiography at diagnosis including PR-interval, isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) for electrical, systolic, and diastolic function, respectively. Controls were assessed at recruitment. Perinatal outcomes were obtained from delivery books. The main outcome was the presence of PR-interval prolongation or first-degree fetal heart block, and echographic signs of diastolic and systolic dysfunction. RESULTS: Compared to controls, ICP were above upper limit in conjugated bilirubin (2.0% vs. 20.4%; p = 0.008), aspartate aminotransferase (2.0% vs. 24.5%; p = 0.002), and alanine aminotransferase (4.1% vs. 28.6%; p = 0.002). ICP was associated with a higher PR-interval (130 ± 12 ms vs. 121 ± 6 ms; p < 0.0001) with five first-degree fetal heart blocks. IRT was significantly higher in ICP (42 ± 6 ms vs. 37 ± 5 ms; p = 0.0001), with no differences in ICT and ET. PR-interval trend was only positively correlated with IRT in ICP pregnancies (p = 0.04 and p = 0.34, in ICP and controls, respectively). CONCLUSIONS: Our study demonstrates that fetuses affected by maternal ICP are associated with electrical and diastolic myocardial dysfunction. More studies focused on antenatal and postnatal functional echocardiography are necessary to validate our results and consider these markers in the clinical management of ICP pregnancies.

Occurrence of persistent atrial fibrillation during pacing for sinus node disease: The influence of His bundle pacing versus managed ventricular pacing.

INTRODUCTION: In patients with sinus node disease (SND), the dual-chamber pacemaker (PM) is programmed in DDDR mode with an algorithm to avoid unnecessary right ventricular (RV) pacing. This pacing mode may prolong PR interval with consequently atrioventricular (AV) asynchrony which is associated with a higher risk of atrial fibrillation (AF). We evaluate whether preserving AV synchrony by setting a fixed AV delay during physiological RV pacing, that is, His bundle pacing (HBP), could reduce the risk of AF occurrence in comparison with a standard pacing mode with an algorithm to avoid unnecessary RV pacing (DDD-VPA). METHODS AND RESULTS: We collected retrospective data from 313 consecutive patients who had undergone PM for SND. The first occurrence of persistent AF (>7 consecutive days) as a function of the pacing mode was evaluated. HBP and DDD-VPA were implemented in 82 and 231 patients, respectively. Persistent AF occurred in 128 (40.9%) patients over a median follow-up of 70 months (67-105). The DDD-VPA pacing mode was significantly correlated with the occurrence of persistent AF only when the basal PR was long (>180 ms). The risk of persistent AF was significantly lower in patients on HBP than in those on DDD-VPA, adjusted HR = .57 (95% CI, .36- .89, p=.014). Other independent predictors of persistent AF occurrence were: A history of AF (HR = 3.91; 95% CI, 2.48-6.19, p = .001), age, and long PR interval (HR = 2.98; 95% CI, 2.00-4.43, p=.001). CONCLUSION: In SND patients and long basal PR interval, the HBP may reduce the risk of persistent AF in comparison with the DDD-VPA.

PR interval prolongation is significantly associated with aortic root abscess: An age- and gender-matched study.

BACKGROUND: Electrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age- and gender-matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis. METHODS: Patients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12-lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre- and post-admission PR interval, was the primary outcome of interest. The patients in the ARA group were age- and gender-matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed. RESULTS: Eighteen patients with surgically confirmed ARA were enrolled. These patients were age- and gender-matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p < .001) groups. The primary outcome measure, delta PR interval, was significantly longer in the ARA group (35 ± 51 ms) than no endocarditis (-5 ± 17 ms) (p = .001) and aortic valve endocarditis groups (0.2 ± 18) (p = .003). CONCLUSIONS: The findings of our study support the notion that the PR interval is more likely to be prolonged in patients with ARA. Since ARA is associated with a high morbidity and mortality, PR interval prolongation in a patient with aortic valve endocarditis should prompt a thorough evaluation for aortic root involvement.

Clinical impact of long PR-interval and presence of late gadolinium enhancement on hospitalized patients with non-ischemic heart failure.

BACKGROUND: The combination of electrical and structural remodeling may have a strong effect on the prognosis of non-ischemic heart failure (HF). We aimed to clarify whether prolonged PR-interval and the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) influence the outcomes of patients with non-ischemic HF. METHODS: We studied 262 consecutive hospitalized patients with non-ischemic HF. In a clinically stable condition, a 12-lead electrocardiogram and CMR were performed, and the clinical characteristics and outcomes were investigated. RESULTS: During the follow-up of 967.7 ± 851.8 days, there were 68 (25.9%) cardiac events (HF or sudden death, re-hospitalization due to HF, or ventricular tachyarrhythmias). In a multivariable analysis, a median rate-adjusted PR (PRa)-interval of ≥173.5 ms and the presence of LGE were associated with cardiac events with a hazard ratio of 1.690 and 2.045 (p = .044 and p = .006, respectively). Study subjects were then divided into four groups based on long (≥173.5 ms) or short (<173.5 ms) PRa-interval and LGE status: short PRa/non-LGE (n = 80), long PRa/non-LGE (n = 72), short PRa/LGE (n = 51), and long PRa/LGE (n = 59). Cardiac events were 16.2% in short PRa/non-LGE, 25.0% in long PRa/non-LGE, 27.4% in short PRa/LGE, and 38.9% in long PRa/LGE (p = .026), respectively. The multivariable Cox proportional hazard analysis showed that long PRa/LGE was an independent predictor for cardiac events compared to short PRa/non-LGE (hazard ratio, 3.378, p = .001). CONCLUSIONS: The combination of a long PRa-interval and the presence of LGE provide a better predictive value of cardiac events in non-ischemic HF.

Association of T66A polymorphism in CASQ2 with PR interval in a Chinese population.

OBJECTIVE: The aim of this study was to explore the relationship between arrhythmia-associated or electrocardiogram (ECG)-associated common variants and PR interval, QRS duration, QTcorrected, and heart rate in a Chinese cohort. METHODS: We studied the association between 26 single-nucleotide polymorphisms (SNPs) and digital ECG data from 379 unrelated Han Chinese individuals collected in an epidemiological survey in Beijing. All subjects were 45 years of age or older and were free of cardiovascular diseases and diabetes. The SNPs were genotyped in a multiplex panel using the Sequenom MassARRAY platform. RESULTS: Missense variant T66A (Thr66Ala, rs4074536) of the CASQ2 gene, which was previously reported to be associated with QRS complex in European populations, was significantly associated with PR interval prolongation in our sample (padjusted = 0.006, betaadjusted = 3.983 ms). A two-tailed t test showed that the CC genotype (n = 86) had a significantly longer PR interval (162.9 ± 19.4 ms) than the non-CC genotypes (n = 288, PR interval: 154.6 ± 20.9 ms), with a remarkable difference of 8.2 ms between the groups (p = 0.001). Interestingly, this association between T66A of CASQ2 and PR interval was more evident in females (padjusted = 0.007, betaadjusted = 5.723 ms) than in males (padjusted = 0.177, betaadjusted = 2.725 ms). In addition, rs3822714 in the HAND1 locus might be associated with QRS duration (padjusted = 0.034, betaadjusted = -2.268 ms). CONCLUSION: We identified a novel signal of an association between the CC genotype of T66A in CASQ2 and PR interval prolongation in a Chinese population, particularly in females. This association deserves further exploration given its possible effects on calcium handling in cardiac electrophysiology.

Within-patient comparison of His-bundle pacing, right ventricular pacing, and right ventricular pacing avoidance algorithms in patients with PR prolongation: Acute hemodynamic study.

AIMS: A prolonged PR interval may adversely affect ventricular filling and, therefore, cardiac function. AV delay can be corrected using right ventricular pacing (RVP), but this induces ventricular dyssynchrony, itself harmful. Therefore, in intermittent heart block, pacing avoidance algorithms are often implemented. We tested His-bundle pacing (HBP) as an alternative. METHODS: Outpatients with a long PR interval (>200 ms) and intermittent need for ventricular pacing were recruited. We measured within-patient differences in high-precision hemodynamics between AV-optimized RVP and HBP, as well as a pacing avoidance algorithm (Managed Ventricular Pacing [MVP]). RESULTS: We recruited 18 patients. Mean left ventricular ejection fraction was 44.3 ± 9%. Mean intrinsic PR interval was 266 ± 42 ms and QRS duration was 123 ± 29 ms. RVP lengthened QRS duration (+54 ms, 95% CI 42-67 ms, p < .0001) while HBP delivered a shorter QRS duration than RVP (-56 ms, 95% CI -67 to -46 ms, p < .0001). HBP did not increase QRS duration (-2 ms, 95% CI -8 to 13 ms, p = .6). HBP improved acute systolic blood pressure by mean of 5.0 mmHg (95% CI 2.8-7.1 mmHg, p < .0001) compared to RVP and by 3.5 mmHg (95% CI 1.9-5.0 mmHg, p = .0002) compared to the pacing avoidance algorithm. There was no significant difference in hemodynamics between RVP and ventricular pacing avoidance (p = .055). CONCLUSIONS: HBP provides better acute cardiac function than pacing avoidance algorithms and RVP, in patients with prolonged PR intervals. HBP allows normalization of prolonged AV delays (unlike pacing avoidance) and does not cause ventricular dyssynchrony (unlike RVP). Clinical trials may be justified to assess whether these acute improvements translate into longer term clinical benefits in patients with bradycardia indications for pacing.

Need for pacing in patients who qualify for an implantable cardioverter-defibrillator: Clinical implications for the subcutaneous ICD.

BACKGROUND: Implantation of the subcutaneous implantable cardioverter-defibrillator (S-ICD) is spreading and has been shown to be safe and effective; however, it does not provide brady-pacing. Currently, data on the need for brady-pacing and cardiac resynchronization therapy (CRT) implantation in patients with ICD indication are limited. METHODS: The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II enrolled post-MI patients with reduced ejection fraction (EF ≤ 35%), randomized to either an implantable cardioverter-defibrillator (ICD) or conventional medical therapy. Kaplan-Meier analyses and multivariate Cox models were performed to assess the incidence and predictors of pacemaker (PM), or CRT implantation in the conventional arm of MADIT-II, after excluding 32 patients (6.5%) with a previously implanted PM. RESULTS: During the median follow-up of 20 months, 24 of 458 patients (5.2%) were implanted with a PM or a CRT (19 PM, 5 CRT). Symptomatic sinus bradycardia was the primary indication for PM implantation (n = 9, 37%), followed by AV block (n = 5, 21%), tachy-brady syndrome (n = 4, 17%), and carotid sinus hypersensitivity (n = 1, 4%). Baseline PR interval >200 ms (HR = 3.07, 95% CI: 1.24-7.57, p = .02), and CABG before enrollment (HR = 6.88, 95% CI: 1.58-29.84, p = .01) predicted subsequent PM/CRT implantation. Patients with PM/CRT implantation had a significantly higher risk for heart failure (HR = 2.67, 95% CI = 1.38-5.14, p = .003), but no increased mortality risk (HR = 1.06, 95% CI = 0.46-2.46, p = .89). CONCLUSION: The short-term need for ventricular pacing or CRT implantation in patients with MADIT-II ICD indication was low, especially in those with a normal baseline PR interval, and such patients are appropriate candidates for the subcutaneous ICD.

Comparison of PR, QRS, and QT interval measurements by seven ECG interpretation programs.

BACKGROUND: Electrocardiograph-generated measurements of PR, QRS, and QT intervals are generally thought to be more precise than manual measurements on paper records. However, the performance of different programs has not been well compared. METHODS: Routinely obtained digital electrocardiograms (ECGs), including over 500 pediatric ECGs, were used to create over 2000 10 s analog ECGs that were replayed through seven commercially available electrocardiographs. The measurements for PR interval, QRS duration, and QT interval made by each program were extracted and compared against each other (using the median of the programs after correction for program bias) and the population mean values. RESULTS: Small but significant systematic biases were seen between programs. The smallest and largest variation from the population mean differed by 4.7 ms for PR intervals, 5.8 ms for QRS duration, and 12.4 ms for QT intervals. In pairwise comparison programs showed similar accuracy for most ECGs, with the average absolute errors at the 75th percentile for PR intervals being 4-6 ms from the median, QRS duration 4-8 ms, and QT interval 6-10 ms. However, substantial differences were present in the numbers and extent of large, clinically significant errors (e.g at the 98th percentile), for which programs differed by a factor of two for absolute errors, as well as differences in the mix of overestimations and underestimations. CONCLUSIONS: When reading digital ECGs, users should be aware that small systematic differences exist between programs and that there may be large clinically important errors in difficult cases.

Effect of PR interval and pacing mode on persistent atrial fibrillation incidence in dual chamber pacemaker patients: a sub-study of the international randomized MINERVA trial.

AIMS: Per standard of care, dual-chamber pacemakers are programmed in DDDR mode with fixed atrioventricular (AV) delay or with long AV delay to minimize ventricular pacing. We aimed to evaluate whether the PR interval may be a specific criterion of choice between standard DDDR, to preserve AV synchrony in long PR patients, and managed ventricular pacing (MVP), to avoid ventricular desynchronization imposed by right ventricle apical pacing, in short PR patients. METHODS AND RESULTS: In the MINERVA trial, 1166 patients were randomized to Control DDDR, MVP, or atrial anti-tachycardia pacing plus MVP (DDDRP + MVP). We evaluated the interaction of PR interval with pacing mode by comparing the risk of atrial fibrillation (AF) longer than 7 consecutive days as a function of PR interval. Out of 906 patients with available data, the median PR interval was 180 ms. The PR interval was found to significantly (P = 0.012) interact with pacing mode for AF incidence: the risk of AF > 7 days was lower [hazard ratio (HR) 0.58, 95% confidence interval (95% CI) 0.34-0.99; P = 0.047] in patients with short PR (shorter than median PR) if programmed in MVP mode compared with DDDR mode and it was lower (HR 0.65, 95% CI 0.43-0.99; P = 0.049) in patients with long PR (equal to or longer than median PR) if programmed in DDDR mode compared with MVP. CONCLUSION: Our data show that PR interval may be used as a selection criterion to identify the optimal physiological pacing mode. Persistent AF incidence was lower in short PR patients treated by right ventricular pacing minimization and in long PR patients treated by standard dual-chamber pacing.

PR Prolongation predicts inadequate resynchronization with biventricular pacing in left bundle branch block.

BACKGROUND: PR interval prolongation is associated with poor outcome after cardiac resynchronization therapy (CRT) among patients with left bundle branch block (LBBB) but the mechanisms are unknown. We investigated clinical outcomes, electrocardiogram (ECG), and echocardiogram changes after CRT by PR interval. METHODS: This is a retrospective study of CRT recipients with a baseline ejection fraction ≤35% and ECG showing sinus rhythm and LBBB. Patients were stratified by baseline PR interval quartile and the primary combined endpoint was time to heart transplantation, left ventricular assist device (LVAD) implantation, or death. ECG, echocardiogram, and clinical variables were compared to identify mechanisms for observed differences in outcomes. RESULTS: Of 291 eligible patients, the mean age was 65 years, 60% were male, and 19% had prior atrial fibrillation. Patients with PR prolongation (quartile 4, PR > 200 ms) more frequently had a history of atrial fibrillation, coronary artery bypass graft surgery, prior implantable cardioverter defibrillator implantation, and use of amiodarone than patients in PR quartiles 1-3. A PR > 200ms was associated with an adjusted hazard ratio of 1.7 (95% CI: 1.1-2.5) for the primary endpoint. Patients with PR > 200 ms had less reduction in QRS duration and QRS area after CRT while having more increase in QT and QTc intervals than patients with PR ≤ 200 ms. No major differences were observed in echocardiography by baseline PR interval quartiles. CONCLUSIONS: PR prolongation predicts shorter survival free of heart transplantation or LVAD implantation in patients with LBBB. This may be due to inadequate ventricular resynchronization.

Association of vitamin D deficiency with electrocardiographic markers of left atrial abnormalities.

OBJECTIVE: Electrocardiographic markers of left atrial (LA) abnormalities are linked to increased risk of cardiovascular disease (CVD). We examined the relationship of vitamin D deficiency with prolonged P wave duration and PR interval as markers of LA abnormalities. METHODS: This analysis included 5,894 participants (58.12 ± 12.9 years; 54.7% women; 49.8% non-Hispanic Whites) without clinical CVD from NHANES III. A multivariable logistic regression model was used to examine the association of vitamin D categories (<20 ng/ml, 20-29 ng/ml and >30 ng/ml (reference) with prolonged P wave duration (≥120 ms) and PR interval (≥200 ms). RESULTS: There was an incremental increase in the prevalence of prolonged P wave duration and PR interval across vitamin D categories with the highest prevalence in study participants with vitamin D levels <20 ng/ml, followed by 20-29 ng/ml and then >30 ng/ml (trend p-value < 0.0001). Vitamin D deficiency (<20 ng/ml) was associated with prolonged P wave duration (OR [95% CI]: 1.22 [1.03-1.45], p = 0.02) and prolonged PR interval (OR [95% CI]: 1.48 [1.12-1.97], p = 0.006) in multivariable logistic regression models adjusted for demographics, CVD risk factors, and other potential confounders. These associations were consistent across subgroups stratified by age, sex, and race. CONCLUSIONS: Vitamin D deficiency is associated with an increased risk of LA abnormalities. This association elucidates an alternate pathway through which vitamin D deficiency may increase CVD risk. Whether vitamin D supplementation would improve LA abnormalities requires further investigation.

The relationship between serum potassium concentrations and electrocardiographic characteristics in 163,547 individuals from primary care.

AIMS: Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels. METHODS AND RESULTS: From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged ≥16 years with a first available ECG and a concomitant serum potassium measurement during 2001-2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0-4.1 mmol/L and 4.2-6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.8 ms longer for each mmol/L decrease in potassium (p < 0.0001); T-wave amplitude was 43.1 µV lower for each mmol/L decrease in potassium (p < 0.0001); and MCS was 0.13 higher per mmol/L decrease in potassium (p < 0.001). Moreover, P-wave duration and PR interval were prolonged by 2.7 and 4.6 ms for each mmol/L decrease in potassium (p < 0.0001), respectively. Within the lowest potassium range (2.0-4.1 mmol/L) P-wave amplitude was 3.5 µV higher for each mmol/L decrease in potassium (p < 0.0001). Within the high potassium range associations with the above-mentioned ECG parameters were much weaker.

Short-term effects of fine particulate matter and ozone on the cardiac conduction system in patients undergoing cardiac catheterization.

BACKGROUND: Air pollution-induced changes in cardiac electrophysiological properties could be a pathway linking air pollution and cardiovascular events. The evidence of air pollution effects on the cardiac conduction system is incomplete yet. We investigated short-term effects of particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) and ozone (O3) on cardiac electrical impulse propagation and repolarization as recorded in surface electrocardiograms (ECG). METHODS: We analyzed repeated 12-lead ECG measurements performed on 5,332 patients between 2001 and 2012. The participants came from the Duke CATHGEN Study who underwent cardiac catheterization and resided in North Carolina, United States (NC, U.S.). Daily concentrations of PM2.5 and O3 at each participant's home address were predicted with a hybrid air quality exposure model. We used generalized additive mixed models to investigate the associations of PM2.5 and O3 with the PR interval, QRS interval, heart rate-corrected QT interval (QTc), and heart rate (HR). The temporal lag structures of the associations were examined using distributed-lag models. RESULTS: Elevated PM2.5 and O3 were associated with four-day lagged lengthening of the PR and QRS intervals, and with one-day lagged increases in HR. We observed immediate effects on the lengthening of the QTc interval for both PM2.5 and O3, as well as delayed effects for PM2.5 (lagged by 3 - 4 days). The associations of PM2.5 and O3 with the PR interval and the association of O3 with the QRS interval persisted until up to seven days after exposure. CONCLUSIONS: In patients undergoing cardiac catheterization, short-term exposure to air pollution was associated with increased HR and delays in atrioventricular conduction, ventricular depolarization and repolarization.

The association of the amounts of epicardial fat, P wave duration, and PR interval in electrocardiogram.

BACKGROUND: The relationship of epicardial fat and cardiac arrhythmias has been described in many studies. The association of the amounts of epicardial fat and the characteristics of electrocardiogram (ECG) remains unclear. The purpose of this study was to elucidate the association between the amounts of epicardial fat and the characteristics of ECG. METHODS: A total of 100 consecutive patients who received multi-detector computer tomography (MDCT) were enrolled. The amounts of epicardial fat, including total heart, total atria, total ventricles, right atrium (RA), right ventricle (RV), left atrium (LA), and left ventricle (LV) regions, were measured. The PR interval in lead II, the P wave duration in lead I, the characteristics of inter-atrial conduction block manifested in ECG, the corrected QT interval (QTc) and the QT dispersion of a 12­lead ECG were measured manually by a computer caliper. RESULTS: The PR interval was correlated with the amounts of epicardial fat including total heart, total atria, total ventricles, RA, RV, LA, and LV (R = 0.295, p = 0.003; R = 0.379, p < 0.001; R = 0.284, p = 0.003; R = 0.415, p < 0.001; R = 0.287, p < 0.001; R = 0.33, p < 0.001; R = 0.244, p = 0.014). The P wave duration of lead I was also correlated with the amounts of epicardial fat (R = 0.202, p = 0.043; R = 0.283, p = 0.004; R = 0.225, p = 0.024; R = 0.365, p < 0.001; R = 0.256, p = 0.001; R = 0.20, p = 0.046; R = 0.199, p = 0.048) but the QTc interval and the QT dispersion were not. Inter-atrial conduction block was also associated with the amounts of epicardial fat, including total atria, RA and LA in univariate analysis (odds ratio (OR): 1.04, 95% of confidence interval (CI): 1.01-1.06, p = 0.015; OR: 1.08, 95% CI: 1.02-1.15, p = 0.011; OR: 1.05, 95% CI: 1.01-1.10, p = 0.031). In multivariate analysis of linear regression, the amounts of RA epicardial fat was most significantly associated with the PR interval, and the P wave duration (ß value: 1.30, 95% CI: 0.59-2.02, p < 0.001; ß value: 0.81, 95% CI: 0.34-1.28, p = 0.001). In multivariate analysis of logistic regression, inter-atrial conduction block was also significantly associated with the amounts of RA epicardial fat (odds ratio (OR): 1.08, 95% CI: 1.02-1.15, p = 0.011). CONCLUSIONS: The PR interval, P wave duration and inter-atrial conduction block were associated with the amounts of epicardial fat, which might imply an effect for arrhythmogenesis.