Arterial Stiffness Is Associated With QTc Interval Prolongation in Patients With Heart Failure

Background: A prolonged corrected QT (QTc) interval is a known risk factor for adverse cardiac events. Understanding the determinants and physiologic correlates of QTc is necessary for selecting proper strategies to reduce the risk of adverse events in high-risk patients. We sought to evaluate the role of arterial stiffness in heart failure as a determinant of QTc prolongation. Method: This was an observational study that recruited ambulatory heart failure patients (New York Heart Association Classes I–II) from an outpatient heart failure clinic. In the supine resting position, consented patients underwent noninvasive 12-lead electrocardiograph (ECG) and hemodynamic monitoring using BioZ Dx impedance cardiography. ECGs were evaluated by a reviewer blinded to clinical data, and QTc interval was automatically computed. Patients with pacing or bundle branch block (BBB) were analyzed separately. Strengths of associations were evaluated using Pearson’s r coefficients and multivariate linear regression. Results: The final sample ( N = 44) was 62 ± 13 years of age and 64% male with ejection fraction of 34% ± 12%. At univariate level, QTc interval moderately ( r > .50) correlated with cardiac output, left cardiac work index, systemic vascular resistance, and total arterial compliance in patients with intrinsically narrow QRS complexes. At the multivariate level, increasing systemic vascular resistance and decreasing total arterial compliance remained independent predictors of widening QTc interval in this group ( R2 = .54). No significant correlations were seen in patients with pacing or BBB. Conclusions: In the absence of conduction abnormalities, magnitude of arterial stiffness, an indirect measure of endothelial dysfunction, is associated with QTc interval prolongation.

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Abstract 15631: The Hemodynamic Determinants and Physiologic Correlates of QTc Interval Using Impedance Cardiography in Heart Failure

Circulation ◽

10.1161/circ.132.suppl_3.15631 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Fadi Khraim ◽

Rodolfo Pike ◽

Jennifer Williams ◽

Salah S Al-Zaiti

Keyword(s):

Heart Failure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Impedance Cardiography ◽

Arterial Compliance ◽

Qtc Interval ◽

Cardiac Events ◽

Heart Failure Patients ◽

Qrs Duration ◽

Duration Effect

Background: Prolonged QTc interval is a known risk factor for adverse cardiac events, including sudden and non-sudden cardiac death. Understanding the determinants and physiologic correlates of QTc can guide the proper strategy for the primary prevention of sudden death in high risk patients. Methods & Results: This was an observational study that recruited ambulatory heart failure patients (NYHA I-III) from an outpatient clinic in NL, Canada. In supine resting position, consented participants underwent non-invasive 12-lead ECG and hemodynamic monitoring using BioZ Dx Impedance Cardiography (Sonosite Inc., WA, USA). ECGs were evaluated by a reviewer blinded to clinical data. Participants with pacing (n=12) or left bundle branch block (n=9) were excluded. Three measures of interest were automatically computed: (1) QTc interval (i.e., from QRS onset to T offset), (2) QRS duration (i.e., from QRS onset to QRS offset), and (3) JTc (i.e., QTc interval minus QRS duration). Effect sizes were computed using Pearson’s r coefficients. The final sample (n=23) was 62±13 years of age and 70% male with LVEF of 34±10%. The mean QTc was 441±39 milliseconds, and 10 patients (43%) had prolonged QTc (≥450 milliseconds). QTc interval negatively correlated with cardiac output (r= -0.57), and positively correlated with systemic vascular resistance (r= +0.57), as well as thoracic fluid content (r= +0.43). QRS duration alone was not specifically associated with any hemodynamic parameter, but JTc interval positively correlated with total arterial compliance (r=+0.42). Conclusions: In heart failure patients, we interestingly found that increased systemic vascular resistance results in QTc interval prolongation, where repolarization time is specifically influenced by arterial compliance. This suggests potential benefit from antihypertensive therapy targeted at lowering systemic vascular resistance in those with prolonged QTc/JTc. Nevertheless, these intervals need to be interpreted with caution in patients with thoracic fluid overload (e.g., pulmonary edema).

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Influence of critical closing pressure on systemic vascular resistance and total arterial compliance: A clinical invasive study

Archives of Cardiovascular Diseases ◽

10.1016/j.acvd.2017.03.008 ◽

2017 ◽

Vol 110 (12) ◽

pp. 659-666 ◽

Cited By ~ 4

Author(s):

Denis Chemla ◽

Edmund M.T. Lau ◽

Philippe Hervé ◽

Sandrine Millasseau ◽

Mabrouk Brahimi ◽

...

Keyword(s):

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Arterial Compliance ◽

Total Arterial Compliance ◽

Critical Closing Pressure ◽

Closing Pressure

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QRS and QTc interval prolongation in the prediction of long-term mortality of patients with acute destabilised heart failure

Heart ◽

10.1136/hrt.2006.102319 ◽

2007 ◽

Vol 93 (9) ◽

pp. 1093-1097 ◽

Cited By ~ 33

Author(s):

T. Breidthardt ◽

M. Christ ◽

M. Matti ◽

D. Schrafl ◽

K. Laule ◽

...

Keyword(s):

Heart Failure ◽

Qtc Interval ◽

Interval Prolongation ◽

Qtc Interval Prolongation ◽

Long Term Mortality

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Distinct Contribution of Systemic Blood Flow to Hypertension in an African Population Across the Adult Lifespan

Hypertension ◽

10.1161/hypertensionaha.120.14925 ◽

2020 ◽

Vol 76 (2) ◽

pp. 410-419

Author(s):

Angela J. Woodiwiss ◽

Keneilwe N. Mmopi ◽

Vernice Peterson ◽

Carlos Libhaber ◽

Hamza Bello ◽

...

Keyword(s):

Blood Pressure ◽

Stroke Volume ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Pulse Pressure ◽

Arterial Compliance ◽

African Ancestry ◽

Systemic Blood Flow ◽

Age Related ◽

Total Arterial Compliance

Although hypertension in groups of African ancestry is volume-dependent, the relative impact of systemic flow (stroke volume, peak aortic flow [Q]) versus vascular mechanisms (systemic vascular resistance, aortic characteristic impedance [Zc], total arterial compliance) components of arterial load has not been evaluated across the adult age range. In participants of African ancestry (n=824, age=16–99 years, 68.3% female), using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the hemodynamic correlates of age-related increases in blood pressure. Strong independent positive relations between age and stroke volume or peak aortic Q were noted ( P <0.0001), effects associated with ventricular end diastolic volume and aldosterone-to-renin ratios. Age-related increases in mean arterial pressure were associated with stroke volume and not systemic vascular resistance. Although age-Q relations began from early adulthood, initially an inverse association between age and aortic Zc ( P <0.0001) driven by increments in aortic root diameter ( P <0.0001) prevented an enhanced systolic blood pressure and pulse pressure. When Zc began to positively relate to age ( P <0.0001), age-Q relations translated into increases in forward wave pressures and hence systolic blood pressure and pulse pressure. Age relations with pulse pressure were as strongly determined by Q as by Zc or total arterial compliance (0.027±0.001 versus 0.028±0.001 and 0.032±0.003 mm Hg per yearly increase in pulse pressure produced by Q, Zc, and total arterial compliance; P <0.0001). Uncontrolled hypertension (confirmed with 24-hour blood pressure) was determined more by Q, Zc, and total arterial compliance than by increases in systemic vascular resistance ( P <0.0005 for comparison). In conclusion, relationships between age and systemic blood flow contribute markedly to hypertension in groups of African origins.

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Contribution of systemic vascular resistance and total arterial compliance to effective arterial elastance in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00823.2002 ◽

2003 ◽

Vol 285 (2) ◽

pp. H614-H620 ◽

Cited By ~ 85

Author(s):

Denis Chemla ◽

Isabelle Antony ◽

Yves Lecarpentier ◽

Alain Nitenberg

Keyword(s):

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Arterial Compliance ◽

Aortic Pressure ◽

Left Ventricular ◽

Reliable Estimate ◽

Arterial Elastance ◽

Total Arterial Compliance ◽

Arterial Load ◽

Effective Arterial Elastance

The respective contribution of systemic vascular resistance ( R) and total arterial compliance ( C) to the arterial load remains to be established in humans. Effective arterial elastance ( Ea), i.e., the left ventricular end-systolic pressure (LVESP)-over-stroke volume ratio, is a reliable estimate of arterial load. It is widely accepted that Ea mainly relates to mean aortic pressure (MAP) and thus to the R-to- T ratio ( R/ T ratio), where T is cycle length. We tested the contribution of R/ T and 1/ C to Ea in 20 normotensive and 46 hypertensive subjects (MAP range: 84–160 mmHg). The multilinear model applied ( Ea = 1.00 R/ T + 0.42/ C – 0.04; r2 = 0.97). The sensitivity of Ea to a change in R/ T was 2.5 times higher than to a similar change in 1/ C in both normotensive and hypertensive adults. The LVESP was more strongly related to systolic aortic pressure (SAP; r2 = 0.94) than to MAP ( r2 = 0.83), and LVESP matched 90% SAP (bias = 0 ± 5mmHg). An alternative model of Ea is proposed, in which Ea is proportional to the heart rate × SAP product-over-cardiac index ratio whatever the MAP.

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Evaluation of Moxifloxacin in Canine and Non‐Human Primate Telemetry Assays: Comparison of QTc Interval Prolongation by Timepoint and Concentration‐QTc Analysis

Clinical and Translational Science ◽

10.1111/cts.13103 ◽

2021 ◽

Author(s):

Ray W. Chui ◽

Joel Baublits ◽

Fiona A. Chandra ◽

Zack W. Jones ◽

Michael J. Engwall ◽

...

Keyword(s):

Qtc Interval ◽

Interval Prolongation ◽

Qtc Interval Prolongation ◽

Human Primate

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Drugs, QTc Interval Prolongation and Final ICH E14 Guideline

Drug Safety ◽

10.2165/00002018-200528110-00003 ◽

2005 ◽

Vol 28 (11) ◽

pp. 1009-1028 ◽

Cited By ~ 91

Author(s):

Rashmi R Shah

Keyword(s):

Qtc Interval ◽

Interval Prolongation ◽

Qtc Interval Prolongation ◽

Ich E14

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Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes

Scientific Reports ◽

10.1038/s41598-021-84758-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mille K. Lyhne ◽

Andreas Vegge ◽

Gro Klitgaard Povlsen ◽

Rita Slaaby ◽

Jonas Kildegaard ◽

...

Keyword(s):

Plasma Glucose ◽

Fold Increase ◽

Diabetic Group ◽

Large Animal ◽

Qtc Interval ◽

Interval Prolongation ◽

Hyperinsulinaemic Hypoglycaemia ◽

Large Animal Models ◽

Qtc Interval Prolongation ◽

Electrocardiographic Recordings

AbstractThe potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8–1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.

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