Mechanical Alternans Is Associated With Mortality in Acute Hospitalized Heart Failure

Abstract

Background Acute hospitalized heart failure (AHHF) is associated with 40–50% risk of death or rehospitalization within 6 months post-discharge. Timely (before hospital discharge) risk stratification of AHHF patients is crucial. We hypothesized that mechanical alternans (MA) and T-wave alternans (TWA) is associated with post-discharge outcomes in AHHF patients.. Methods and Results A prospective cohort study was conducted in the intensive cardiac care unit (ICCU) and enrolled 133 patients (59.6±15.7 y.; 65% men) admitted with AHHF. Surface ECG and peripheral arterial blood pressure waveform via arterial line were recorded continuously during the ICCU stay. MA and TWA were measured by enhanced modified moving average method. All-cause death or heart transplant served as a combined primary endpoint. MA was observed in 28 patients (25%), while TWA was detected in 33 patients (33%). If present, MA was tightly coupled with TWA. Mean TWA amplitude was larger in patients with both TWA and MA, as compared to patients with lone TWA (median 37(IQR 26–61) vs. 22(21–23) μV; P=0.045). After a median of 10 months post-discharge, 42 (38%) patients died and 2 had heart transplants. MA was associated with the primary endpoint in univariable Cox model [HR 1.84(95%CI 1.00–3.40); P=0.05], and after adjustment for left ventricular ejection fraction, NYHA HF class, and implanted ICD/CRT-D device, [HR 2.12 (95%CI 1.13–3.98); P=0.020]. TWA without consideration of simultaneous MA was not significantly associated with primary endpoint (HR 1.42; (95%CI 0.77–2.64); P=0.260). Conclusion MA is independently associated with outcomes in AHHF. Clinical Trial Registration Information URL:http://www.clinicaltrials.gov. Unique identifier:

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

“…The patients in which only MTWA were detectable may either have less severe reductions in thin filament activation or no abnormalities at all, and thus have smaller and undetectable pressure alternans. Furthermore, one study has shown that the magnitude of MTWA in patients with both MTWA and pressure alternans is larger than in patients with only MTWA (Kim et al, 2014), suggesting that if those patients had reduced thin filament activation as we speculated, then that would enhance the magnitude of MTWA, in agreement with our results (Figure 5). …”

“…Here we demonstrated that heart failure-induced mechanical remodeling of parameters that modify thin filament activation can both exacerbate and diminish FORCE-ALT, CA-ALT, and APV-ALT. These results could explain the results of some studies which have revealed two different populations of patients with alternans: those with both MTWA and pressure alternans and those with only MTWA (Kim et al, 2014; Kodama et al, 2001; Selvaraj et al, 2011). The patient population with both types of alternans could have calcium handling abnormalities and reduced thin filament activation, which would (as our results suggest) result in larger and thus more easily detectable pressure alternans.…”

“…In addition, a study conducted during normal sinus rhythm found that patients with pressure alternans had significantly slower heart rates than those without (81.0 bpm vs 93.1 bpm) (Kim et al, 2014). 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.…”

“…Alternatively, noninvasively measured pressure alternans, defined as the beat-to-beat oscillation of the amplitude of systolic pressure, has been found to be a predictor of worsening heart failure and increased cardiac mortality (Hirashiki et al, 2010; Hirashiki et al, 2006; Ito et al, 2012; Kashimura et al, 2014; Kim et al, 2014; Selvaraj et al, 2011). Pressure alternans also occurs simultaneously with MTWA in patients at near resting heart rates, thus indicating that pressure alternans, which have higher signal-to-noise ratio (Selvaraj et al, 2011), may be a better predictor of the propensity for ventricular arrhythmias and sudden cardiac death, however the mechanisms remain unknown.…”

Correlation between the high-frequency content of the QRS on murine surface electrocardiogram and the sympathetic nerves density in left ventricle after myocardial infarction: Experimental study

“…Modified moving average and correlation methods were used to measure TWA, as previously described [15]. …”