The Clinical Importance of Prolonged PR Interval

Practicing PR interval is one of the most important things you can do to help prevent heart disease. This is because it is a tool that can help you determine your heart’s rhythm. It also can help determine whether you are at risk for cardiovascular problems such as atrial fibrillation or heart failure.

Measurement

Traditionally, the measurement of PR interval has been considered benign, but recent studies have suggested that prolongation of the interval may increase mortality and morbidity. The present study sought to determine the clinical importance of a prolonged PR interval in middle-aged individuals. It assessed the risk of sudden cardiac death and associated risk factors in apparently healthy middle-aged men and women.

Compared to individuals with normal PR intervals, patients with long intervals had increased rates of cardiovascular and death events. It also showed that a longer PR interval was associated with a higher incidence of hypertension, arrhythmic events, and pacemaker implantation. However, the association between the PR interval and all-cause mortality was weak.

The Framingham Heart Study, a prospective community-based cohort, compared the relationship between PR interval and several risk factors. Participants underwent 12-lead electrocardiography every four years. Each ECG included measurement of the PR, the QT, and the ST segment. In addition, the occurrence of a first-degree atrioventricular block (AVB) was investigated. The occurrence of a first-degree AVB is a common event in clinical practice, but its prognostic significance remains ambiguous.

The Multiethnic Study of Atherosclerosis, another large multi-ethnic study, investigated the association between PR and the incidence of coronary heart disease. It looked at 1832 apparently healthy men and women aged 40 to 59 years. Several sub analyses were performed, including a comparison of the PR interval with the RR interval and the kh2 test. However, the results of the study were not altered by multivariate adjustments.

The Multiethnic Study of atherosclerosis, a longitudinal study of middle-aged and elderly individuals, also investigated the relationship between PR and cardiovascular morbidity. The onset of adverse outcomes began to increase at 150 Ms. The kh2 test was performed to compare differences between groups. The smallest measurable difference was found in the ratio of the height of the ST segment to the height of the T wave in leads II, III, and aVF.

In the Framingham Heart Study, a long interval was associated with increased risks of mortality, coronary heart disease, and atrial fibrillation. However, the association was not consistent across all age groups and did not hold up well when examined separately for men and women.

Association with atrial fibrillation

During the last several years, several studies have shown that a prolonged PR interval may be associated with an increased risk of developing atrial fibrillation. However, it is unclear whether this association is due to slowed interatrial conduction or a different underlying pathology. These studies have used different methods to test this hypothesis, and the results have been mixed.

The Multiethnic Study of Atherosclerosis examined the relationship between the PR interval and measures of cardiovascular disease. Specifically, the study included 4962 subjects with baseline data. During follow-up, 440 participants developed atrial fibrillation during eight-year windows. The study found that the PR interval was significantly associated with the risk of AF during follow-up. However, the pooled HRs for incident AF were 1.30. This finding was supported by sensitivity analysis, which found that removing the PR interval from the model did not change the association of familial AF.

One study used a Cox proportional hazard model to examine the association between the PR interval and arrhythmic events. This study showed that a PR interval of longer than 200 milliseconds was associated with an increased risk of AF. In addition, a longer PR interval was also associated with an increased risk of death. The study also found that the incidence of AF increased with the use of a pacemaker.

The Framingham Heart Study, which has been followed for decades, included a large number of participants. Almost seventy-five percent of participants were female. They had a mean age of 47 years when they were enrolled. The study used a reproducible electrocardiogram measurement protocol. The participants underwent a 12-lead electrocardiography every 2 years. The study also included a surface electrocardiogram. Participants were followed through 2007.

Another study examined a common SCN5A variant that is associated with a shorter PR interval among African Americans. This study also found that a shorter PR interval was associated with an increased risk of AF. The authors suggested that this common SCN5A variant may be related to a slowing of interatrial conduction.

A PR interval is a period of propagating impulse time from the onset of the P wave to the onset of the QRS complex. A PR interval of longer than 200 milliseconds is considered a first-degree AV block.

Association with pacemaker implantation

Several studies in the general population have shown a correlation between PR interval prolongation and risk of atrial fibrillation and pacemaker implantation. However, the clinical importance of this phenomenon remains unclear. The present study sought to clarify the clinical significance of PR prolongation in the middle-aged population. Specifically, the study aimed to investigate whether patients with heart failure have a greater risk of PR prolongation than healthy individuals.

This study is the largest investigation of PR interval prolongation in the general population. The study involved 92,340 individuals of European ancestry from 31 studies. The data was used to identify 44 loci that may contribute to the risk of PR prolongation and/or atrial fibrillation.

The top locus on chromosome 3 is associated with atrial premature beats and P-wave duration. It maps to two cardiac sodium channel gene (SCN5A and SCN10A) that play critical roles in cardiac electrophysiology. Other loci associated with PR interval include CAMK2D and MYH6.

PR-prolonging variants in these loci play an important role in cardiac electrophysiology. A variant near TBX5 and TBX3 sit close together on chromosome 12. This variant prolongs QRS duration and reduces AF risk. It has also been associated with cardiovascular and cardiac mortality.

The genome-wide association study (GWAS) included 92,340 individuals of European ancestry. The 1601 SNPs were mapped to 44 independent loci. These loci were classified into three categories. Specifically, all models were adjusted for age, body mass index, smoking, and hypertension. 61 non-redundant signals were identified in 44 loci. These signals were examined for the effect on the PR interval, QRS duration, heart rate, and AF.

PR interval is a commonly measured parameter that is related to cardiac abnormalities and mortality. Studies have shown that patients with heart failure with reduced ejection fraction are more likely to have PR prolongation. However, these findings are less consistent when patients are older. Nevertheless, this study showed that PR interval prolongation is a risk factor for AF and pacemaker implantation in both the young and the elderly.

The association between the PR interval and atrial fibrillation was statistically significant. However, it was not associated with increased mortality. Despite this finding, further studies are necessary to determine appropriate follow-up for PR prolongation.

Genetics

Several genome-wide association studies have identified PR interval as a genetic variable that is associated with atrial fibrillation. This phenotype has also been implicated as a risk factor for stroke and heart failure. Currently, the genetics of the PR interval is being studied in several human populations, including European and African Americans. Despite the fact that these populations share a common ancestry, the genetics of the PR interval in African Americans differ from those in Europeans.

Genetic studies have implicated cardiac-expressed ion channels, cardiac developmental transcription factors, and signaling molecules. These genes are overrepresented in diseases related to the heart block and arrhythmias. Many of these genes are also associated with cardiac conduction and cardiac chamber development.

These findings suggest that cardiac conduction is heritable. However, the genetics of PR interval are complex and many SNPs contribute only modest amounts to the trait’s heritability. Consequently, there is limited power in GWAS to detect the contributions of small effect sizes.

Genome-wide association studies have identified 44 loci that are associated with PR interval. These loci reveal previously unknown biological processes, including transcription factors involved in cardiac development, sarcomeric proteins involved in cardiac electrophysiology, and cardiac sodium channels. Many of the loci regulate atrial/atrioventricular depolarization. In addition, some of the index SNPs have been associated with gene-expression levels. In addition, several loci are associated with other phenotypes that are related to cardiac conduction, such as atrioventricular conduction, heart rate, and JT duration.

Two SCN5A loci are important in cardiac electrophysiology, as common variants have been associated with cardiac depolarization and conduction defects. However, subsequent associations are unknown with electroanatomical remodeling and response to catheter ablation. These SCN5A variants are associated with prolonged QRS and PR intervals.

In a genome-wide association study, the DNA of over 92,000 European and African Americans were examined for genetic variations associated with the PR interval, QRS duration, heart rate, and JT duration. The study included 1601 SNPs that mapped to 44 loci. Most SNPs were classified as benign by PolyPhen-2. However, the study had limited power to identify associations among European-descent individuals. In addition, 16 of the 44 loci were replicated among African Americans.

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