Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force–frequency relationship and enhanced poststimulation potentiation

Kashimura, Takeshi; Kodama, Makoto; Tanaka, Komei; Sonoda, Koji; Watanabe, Satoru; Ohno, Yukako; Tomita, Makoto; Obata, Hiroaki; Mitsuma, Wataru; Ito, Masahiro; Hirono, Shuichi; Hanawa, Haruo; Aizawa, Yoshifusa

doi:10.1007/s00380-012-0251-8

Cited by 5 publications

(6 citation statements)

References 33 publications

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“…Fig. 6 shows a qualitative trend of MA magnitude dependence on heart ratevery similar to what is present in [7], where MA generated through atrial pacing also shows a heart rate dependent peak magnitude. We believe this is an area that needs to be further examined, as literature provides little information on this.…”

Section: Discussionsupporting

confidence: 63%

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Non-Invasive Detection of Mechanical Alternans Utilizing Photoplethysmography

Besleaga

Badiani

Lloyd

et al. 2019

IEEE J. Biomed. Health Inform.

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Background and Significance: Mechanical alternans (MA) is a biomarker associated with mortality and life-threatening arrhythmias in heart failure patients. Despite showing prognostic value, its use is limited by the requirement of measuring continuous blood pressure (BP), which is costly and impractical. Objective: To develop and test, for the first time, non-invasive MA surrogates based on photoplethysmography (PPG). Methods: Continuous BP and PPG were recorded during clinical procedures and tests in 35 patients. MA was induced either by ventricular pacing (Group A, N=19) or exercise (Group B, N=16). MA was categorized as sustained or intermittent if MA episodes were observed in at least 20 or between 12 to 20 consecutive beats, respectively. Eight features characterizing pulse morphology were derived from the PPG and MA surrogates were evaluated. Results: Sustained alternans was observed in 9 patients (47%) from Group A, whereas intermittent alternans was observed in 13 patients (68%) from Group A and in 10 patients (63%) from Group B. The PPG-based MA surrogate showing the highest accuracy, V'M, was based on the maximum of the first derivative of the PPG pulse. It detected both sustained and intermittent MA with 100% sensitivity and 100% specificity in Group A and intermittent MA with 100% sensitivity and 83% specificity in Group B. Furthermore, the magnitudes of MA and its PPG-based surrogate were linearly correlated (R 2 =0.83, p<0.001). Conclusion: MA can be accurately identified non-invasively through PPG analysis. This may have important clinical implications for risk stratification and remote monitoring.

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Section: Discussionsupporting

confidence: 63%

“…A threshold is commonly employed to discard low magnitude alternans, i.e. 4mmHg [3] for systolic BP, 100mmHg/s [7] for max dP/dt, particularly in clinical studies. However, there are also studies looking at microsystolic blood pressure alternans (MBPA) [8] which consider alternans of all magnitudes.…”

Section: A Definition Of Mechanical Alternansmentioning

confidence: 99%

Non-Invasive Detection of Mechanical Alternans Utilizing Photoplethysmography

Besleaga

Badiani

Lloyd

et al. 2019

IEEE J. Biomed. Health Inform.

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“…That same study also showed that patients with both MTWA and pressure alternans had slower heart rates than those with only MTWA (81.0 bpm vs 92 bpm, not statistically significant), suggesting that patients with only MTWA may have had small yet undetectable pressure alternans due to the alternans magnitude being markedly reduced at faster heart rates. One study further supported this hypothesis by showing that the amplitude of pressure alternans declined at increasingly faster pacing rates for four patients, three of whom lost pressure alternans when pacing rates exceeded 120, 130 and 140 bpm (500, 462, 400 ms) respectively (Kashimura et al, 2013). The present study provided support of this finding, since we demonstrated that FORCE-ALTM was greatest at slower pacing rates (>109 bpm) and declined significantly at faster pacing rates (<109 bpm).…”

Section: Discussionmentioning

confidence: 92%

Rate-dependent force, intracellular calcium, and action potential voltage alternans are modulated by sarcomere length and heart failure induced-remodeling of thin filament regulation in human heart failure: A myocyte modeling study

Zile

Trayanova

2016

Progress in Biophysics and Molecular Biology

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Microvolt T-wave alternans (MTWA) testing identifies heart failure patients at risk for lethal ventricular arrhythmias at near-resting heart rates (<110 beats per minute). Since pressure alternans occurs simultaneously with MTWA and has a higher signal to noise ratio, it may be a better predictor of arrhythmia, although the mechanism remains unknown. Therefore, we investigated the relationship between force alternans (FORCE-ALT), the cellular manifestation of pressure alternans, and APV-ALT, the cellular driver of MTWA. Our goal was to uncover the mechanisms linking APV-ALT and FORCE-ALT in failing human myocytes and to investigate how the link between those alternans was affected by pacing rate and by physiological conditions such as sarcomere length and heart failure induced-remodeling of mechanical parameters. To achieve this, a mechanically-based, strongly coupled human electromechanical myocyte model was constructed. Reducing the sarcoplasmic reticulum calcium uptake current (Iup) to 27% was incorporated to simulate abnormal calcium handling in human heart failure. Mechanical remodeling was incorporated to simulate altered thin filament activation and crossbridge (XB) cycling rates. A dynamical pacing protocol was used to investigate the development of intracellular calcium concentration ([Ca]i), voltage, and active force alternans at different pacing rates. FORCE-ALT only occurred in simulations incorporating reduced Iup, demonstrating that alternans in the intracellular calcium concentration (CA-ALT) induced FORCE-ALT. The magnitude of FORCE-ALT was found to be largest at clinically relevant pacing rates (<110 bpm), where APV-ALT was smallest. We found that the magnitudes of FORCE-ALT, CA-ALT and APV-ALT were altered by heart failure induced-remodeling of mechanical parameters and sarcomere length due to the presence of myofilament feedback. These findings provide important insight into the relationship between heart-failure-induced electrical and mechanical alternans and how they are altered by physiological conditions at near-resting heart rates.

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“…We have previously reported that idiopathic dilated cardiomyopathy (DCM) patients with MA had a smaller increase in left ventricular dP/dt during tachycardia (impaired force‐frequency relationship [FFR]) and a larger increase in left ventricular dP/dt of the first beat after tachypacing (enhanced PSP) than DCM patients without MA, but the mechanism of the impairment and the enhancement were unknown. Now that patients with MA showed a steep mechanical restitution at BCI in this study, impaired FFR is considered to be caused by relative refractoriness during tachycardia, and enhanced PSP is considered to be caused by restitution of the refractoriness after a longer coupling interval.…”

Section: Discussionmentioning

confidence: 99%

“…AA at a pacing rate of 100/min (AA100) and the maximal AA (AA max) of each patient were determined by the incremental right atrial pacing. Although we had defined MA as AA of 100 mm Hg/s or more in our previous paper, MA of AA less than 100 mm Hg/s are involved in this study in order to examine quantitative correlations between MA and contractile properties.…”

Section: Methodsmentioning

confidence: 99%