Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults

Straus, Sabine M. J. M.; Kors, Jan A.; Bruin, Marie L. De; Hooft, C; Hofman, Albert; Heeringa, Jan; Deckers, Jaap W.; Kingma, J. Herre; Sturkenboom, Miriam; Stricker, Bruno H. Ch.; Witteman, Jacqueline C. M.

doi:10.1016/j.jacc.2005.08.067

Cited by 707 publications

(613 citation statements)

References 33 publications

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“…More importantly, ECG data obtained from radiotelemetry recording demonstrated that in vivo transfection of Ca v 2.2‐α shRNA into AVG neurons not only increased the QT interval, QTc interval, QTd, QTcd, and Tpe but also induced a spontaneous ventricular tachyarrhythmia in conscious rats (Figures 6 and 7). It has been found that prolongation of the QT and QTc intervals, increase of the QTd and QTcd (a marker of spatial heterogeneity of ventricular repolarization), and prolonged Tpe (a marker of transmural dispersion of ventricular repolarization) are associated with increased risk of malignant ventricular arrhythmias and sudden cardiac death 49, 50, 51, 52. The results in the present study provide direct evidence that blunted ventricular vagal activity increases the susceptibility to ventricular arrhythmias and induces ventricular arrhythmias.…”

Section: Discussionsupporting

confidence: 62%

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Zhang

Cao

et al. 2018

JAHA

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BackgroundAttenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N‐type Ca2+ channel α‐subunits (Cav2.2‐α) and N‐type Ca2+ currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the AVG. In this study we tested whether a decrease in N‐type Ca2+ channels in AVG neurons contributes to ventricular arrhythmogenesis.Methods and ResultsLentiviral Cav2.2‐α shRNA (2 μL, 2×107 pfu/mL) or scrambled shRNA was in vivo transfected into rat AVG neurons. Nontransfected sham rats served as controls. Using real‐time single‐cell polymerase chain reaction and reverse‐phase protein array, we found that in vivo transfection of Cav2.2‐α shRNA decreased expression of Cav2.2‐α mRNA and protein in rat AVG neurons. Whole‐cell patch‐clamp data showed that Cav2.2‐α shRNA reduced N‐type Ca2+ currents and cell excitability in AVG neurons. The data from telemetry electrocardiographic recording demonstrated that 83% (5 out of 6) of conscious rats with Cav2.2‐α shRNA transfection had premature ventricular contractions (P<0.05 versus 0% of nontransfected sham rats or scrambled shRNA‐transfected rats). Additionally, an index of susceptibility to ventricular arrhythmias, inducibility of ventricular arrhythmias evoked by programmed electrical stimulation, was higher in rats with Cav2.2‐α shRNA transfection compared with nontransfected sham rats and scrambled shRNA‐transfected rats.ConclusionsA decrease in N‐type Ca2+ channels in AVG neurons attenuates vagal control of ventricular myocardium, thereby initiating ventricular arrhythmias.

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Section: Discussionsupporting

confidence: 62%

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Zhang

Cao

et al. 2018

JAHA

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“…In our study, women with SCD had a mean QTc of 446±27 ms. It is important to note that healthy adult women are known to have longer QT than men; the upper limit for QTc is 450 ms for women but only 430 ms for men 22, 24. QTc of >470 ms was not predictive of SCD among women without CAD ( P =0.09), probably due to loss of statistical power in this binary specification given relatively low event rates.…”

Section: Discussionmentioning

confidence: 94%

“…Longer QTc is well known to be independently associated with SCD in men and women 6, 22. In the case‐control Oregon Sudden Unexpected Death Study of patients with CAD (40% women), QTc was longer in those with SCD compared with controls (450±45 versus 433±37 ms, P <0.0001), and abnormally prolonged QTc was associated with a 5‐fold increased risk of SCD 23.…”

Section: Discussionmentioning

confidence: 99%

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study

Mehta

Johnson

Kenkre

et al. 2017

JAHA

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BackgroundSudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study.Methods and ResultsOverall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non‐SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person‐hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P<0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively (P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (P=0.018) and longer corrected QT interval (P=0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD (P=0.033).Conclusions SCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.

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“…Finally, an extensive dataset from many clinical settings has implicated QT prolongation as a predictor of subsequent mortality; these include convalescence from acute myocardial infarction, 5 diabetes, advancing age, chronic heart failure, autonomic dysfunction, hypertrophic cardiomyopathy, patients awaiting heart transplantation, antihypertensive therapy, and muscular dystrophy.…”

Section: Qt Interval Prolongation Is Associated With Arrhythmiasmentioning

confidence: 99%

Keep the QT interval: It is a reliable predictor of ventricular arrhythmias

Roden

2008

Heart Rhythm

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The cardiovascular community understands that the QT interval is the surface electrocardiographic representation of ventricular repolarization. However, despite tremendous advances in our understanding of the molecular and cellular basis for cardiac repolarization and its surface ECG representation, clinicians, regulators, and drug developers are increasingly faced with uncertainty over the best way to interpret this parameter. The evidence described below demonstrates that• Prolongation of the QT interval is a reliable predictor of ventricular arrhythmias in some settings, and may be less predictable in others• The arrhythmogenic potential of a given degree of QT prolongation varies among individuals and drugs. Further, the relationship between QT prolongation and arrhythmia susceptibility is non-linear. Multiple mechanisms may underlie QT prolongation, and these may carry different arrhythmogenic potential.• There is little doubt that further understanding of the cellular and molecular mechanisms underlying repolarization hold the promise of developing better indices of the arrhythmogenic potential of abnormalities of repolarization, but that science has not yet matured A caveat: The QT interval is hard to measureMeasuring the QT is hard enough when it is normal, and it is almost impossible to come up with a workable number in the face of common disease-associated ECG changes such as diffuse ST segment changes, inverted T-waves, small or large U-waves, or pauses (see Figure 1). A second problem is rate: while there is absolutely no doubt that action potential durations in ventricular tissue, and the QT interval, are exquisitely dependent on previous cycle length or cycle lengths, the "best" method to correct for rate, and thus allow QT intervals recorded at different rates to be compared, is not known. Indeed, comparing two "rate-corrected" QT values presupposes that whatever the intervention between the two recordings -often a drug -itself has no effect on rate. Further, even if a drug has no direct effect on rate, common conditions for which drugs are prescribed may be associated with increases in heart rate (e.g. due to fever or to autonomic activation); any effective drug may thus affect heart rate indirectly.

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Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults

Abstract: Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.

Cited by 707 publications

References 33 publications

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study

Keep the QT interval: It is a reliable predictor of ventricular arrhythmias

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Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults

Abstract: Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.

Cited by 707 publications

References 33 publications

Reduced N‐Type Ca 2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Reduced N‐Type Ca 2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study

Keep the QT interval: It is a reliable predictor of ventricular arrhythmias

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Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis