Death In Myocardial Infarction Patients Research Articles

Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury

BackgroundCathelicidins are a major group of natural antimicrobial peptides which play essential roles in regulating host defense and immunity. In addition to the antimicrobial and immunomodulatory activities, recent studies have reported the involvement of cathelicidins in cardiovascular diseases by regulating inflammatory response and microvascular dysfunction. However, the role of cathelicidins in myocardial apoptosis upon cardiac ischemia/reperfusion (I/R) injury remains largely unknown.MethodsCRAMP (cathelicidin-related antimicrobial peptide) levels were measured in the heart and serum from I/R mice and in neonatal mouse cardiomyocytes treated with oxygen glucose deprivation/reperfusion (OGDR). Human serum cathelicidin antimicrobial peptide (LL-37) levels were measured in myocardial infarction (MI) patients. The role of CRAMP in myocardial apoptosis upon I/R injury was investigated in mice injected with the CRAMP peptide and in CRAMP knockout (KO) mice, as well as in OGDR-treated cardiomyocytes.ResultsWe observed reduced CRAMP level in both heart and serum samples from I/R mice and in OGDR-treated cardiomyocytes, as well as reduced LL-37 level in MI patients. Knockdown of CRAMP enhanced cardiomyocyte apoptosis, and CRAMP KO mice displayed increased infarct size and myocardial apoptosis. In contrast, the CRAMP peptide reduced cardiomyocyte apoptosis and I/R injury. The CRAMP peptide inhibited cardiomyocyte apoptosis by activation of Akt and ERK1/2 and phosphorylation and nuclear export of FoxO3a. c-Jun was identified as a negative regulator of the CRAMP gene. Moreover, lower level of serum LL-37/neutrophil ratio was associated with readmission and/or death in MI patients during 1-year follow-up.ConclusionsCRAMP protects against cardiomyocyte apoptosis and cardiac I/R injury via activation of Akt and ERK and phosphorylation and nuclear export of FoxO3a. Increasing LL-37 might be a novel therapy for cardiac ischemic injury.

Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca2+ leakage channel Sec61\u03b1 in mouse hearts

Cardiac fibrosis is an independent risk factor for heart failure and even the leading cause of death in myocardial infarction patients. However, molecular mechanisms associated with the pathogenesis of cardiac fibrosis following myocardial infarction are not yet fully understood. Nogo-C protein ubiquitously expresses in tissues including in the heart. Our previous study found that Nogo-C regulated cardiomyocyte apoptosis during myocardial infarction. In the present study, we found that Nogo-C was upregulated in fibrotic hearts after myocardial infarction and in Ang II- or TGF-β1-stimulated cardiac fibroblasts. Overexpression of Nogo-C in cardiac fibroblasts increased expression of pro-fibrogenic proteins, while knockdown of Nogo-C inhibited the fibrotic responses of cardiac fibroblasts to Ang II- or TGF-β1 stimulation. Functionally, Nogo-C deficiency suppressed pro-fibrogenic proteins in post-myocardial infarction hearts and ameliorated post-myocardial infarction cardiac function. Mechanistically, we found that Nogo-C increased intracellular Ca2+ concentration and buffering Ca2+ totally abolished Nogo-C-induced fibrotic responses. Moreover, overexpression of Nogo-C caused increased Sec61α, the Ca2+ leakage channel on endoplasmic reticulum membrane. Nogo-C interacted with Sec61α on endoplasmic reticulum and stabilized Sec61α protein by inhibiting its ubiquitination. Inhibition or knockdown of Sec61α blocked Nogo-C-induced increase of cytosolic Ca2+ concentration and inhibited Nogo-C- and TGF-β1-induced fibrotic responses in cardiac fibroblasts, suggesting that Nogo-C regulates cardiac fibrosis through interacting with Sec61α to mediate the Ca2+ leakage from endoplasmic reticulum. Thus, our results reveal a novel mechanism underlying cardiac fibrosis following myocardial infarction, and provide a therapeutic strategy for cardiac remodeling related heart diseases.

AMBULATORY ECG-BASED T-WAVE ALTERNANS AND HEART RATE TURBULENCE IN PATIENTS WITH MYOCARDIAL INFARCTION WITH OR WITHOUT DIABETES MELLITUS

ObjectivesMany patients who survive a myocardial infarction (MI) remain at risk of sudden cardiac death despite revascularisation and optimal medical treatment. We used the modified moving average (MMA) method to...

RESEARCH THE VALUE OF THE COMBINATION OF T WAVE ALTERNANS AND NT-PROBNT IN PREDICTING SUDDEN CARDIAC DEATH

Background: Decades of research now link TWA with inducible and spontaneous clinical ventricular arrhythmias. This bench-to-bedside foundation makes TWA, NT-ProBNP a very plausible index of susceptibility to ventricular arrythmia, and motivates the need to define optimal combination of TWA and NT-ProBNP in predicting ventricular arrythmia in myocardial infarction patients. We research this study with 2 targets: 1. To evaluate the role of TWA in predicting sudden cardiac death in myocardial infarction patients. 2. To evaluate the role of NT-ProBNP in predicting sudden cardiac death in myocardial infarction patients 3. Evaluate the role of the combined NT-ProBNP and TWA in predicting sudden cardiac death in myocardial infarction patients. Methods: Prospective study with follow up the mortality in 2 years: 71 chronic myocardial infarction patients admitted to hospital from 5/2009 to 5/20011 and 50 healthy person was done treadmill test to caculate TWA; ECG, echocardiography, NT-ProBNP. Results: Cut-off point of NT-ProBNP in predicting sudden cardiac death is 3168 pg/ml; AUC = 0,86 (95% CI: 0,72 - 0,91); Cut-off point of TWA in predicting sudden cardiac death is 107 µV; AUC = 0,81 (95% CI: 0,69 - 0,87); NT-ProBNP can predict sudden cardiac death with OR= 7,26 (p<0,01); TWA can predict sudden cardiac death with OR= 8,45 (p<0,01). The combined NT-ProBNP and TWA in predicting ventricular arrythmia in heart failure patients: OR= 17,91 (p<0,001). Conclusions: The combined NT-ProBNP and TWA have the best predict value of sudden cardiac death in myocardial infarction patients, compare to NT-ProBNP or TWA alone

Predictability of baroreflex sensitivity induced by phenylephrine injection via frequency domain indices computed from heart rate and systolic blood pressure signals during deep breathing

Diminished baroreflex sensitivity (BRS) is related to increased risk of sudden cardiac death in myocardial infarction patients and can be used as an indicator for risk level. The BRS is traditionally estimated invasively using vasoactive drugs, such as phenylephrine injection. This method has been widely accepted as a standard in clinical research. Due to its clinical importance, alternative BRS assessment methods have been investigated over the years to eliminate the use of drugs. In this study, the BRS obtained by drug-based (pharmacological) assessment was predicted from a subset of non-pharmacological indices computed from heart rate and systolic pressure signals. In the first phase of a two-phase experimental paradigm, 16 subjects were asked to perform two deep breathings with a 2-min delay in between. In the second phase, the BRS was measured by phenylephrine injection. Indices computed from the first phase describing the spectral and time domain properties of the heart rate and systolic pressure signals were used as predictors to estimate the pharmacological BRS of each subject. In addition to individual spectrum of beat-to-beat interval and systolic blood pressure, indices from cross-spectrum were also computed and evaluated as predictors. A leave one out method was employed to estimate the generalization capacity of the system and explore subset of indices, which gives the highest correlation between pharmacological and predicted BRS. Two predictors provided the highest correlation ( r = 0.87, p = 1.16 × 10 −5) with pharmacological BRS. The algorithm selected consistently normalized cross-power about the Mayer frequency and average magnitude square coherence in the high frequency band as predictors. These results indicate that the pharmacological BRS can be estimated from the combination of non-pharmacological spectral indices computed from beat-to-beat interval and systolic blood pressure signals obtained during deep breathing and therefore may eliminate the use of drugs.

Pump failure death and sudden cardiac death in patients with cardiac dysfunction: A search for prognostic predictive factors—A long-term follow-up study

There have been few reports that have analyzed the predictive factors for heart failure death, which is sub-divided into pump failure death and sudden cardiac death, in the long term. We followed 186 consecutive patients with myocardial infarction (MI) and 115 consecutive patients with non-ischemic heart failure (NIHF) during 73+/-3 months. In the MI group, 26 died from pump failure and 12 died from sudden cardiac death. In the NIHF group, 21 died from pump failure and 9 died from sudden cardiac death. Multivariate analysis revealed that the log B-type natriuretic peptide (BNP) was an independent predictor for pump failure death in both groups. In the MI group, the estimated glomerular filtration rate (eGFR) was an independent predictor for sudden cardiac death. Kaplan-Meier analysis revealed that a high BNP level was a risk factor for pump failure death in either MI or NIHF patients. On the other hand, the sudden cardiac death rate was significantly higher in the MI patients with low eGFR than in those with high eGFR. The plasma BNP level is an independent predictor for pump failure death in both MI and NIHF patients. The eGFR is an independent predictor for sudden cardiac death in MI patients.

Are risk factors for sudden death in myocardial infarction patients treated with percutaneous coronary intervention different? Analysis of the PAMI database Bohuslav Finta, Howard Frumin, Judy Boura, Gregg W. Stone, Bruce R. Brody, David A. Cox, Eulogio Garcia, Lori L. Grines, Kimberly A. Skelding, Cindy L. Grines. William Beaumont Hospital, Royal Oak, MI

Are risk factors for sudden death in myocardial infarction patients treated with percutaneous coronary intervention different? Analysis of the PAMI database Bohuslav Finta, Howard Frumin, Judy Boura, Gregg W. Stone, Bruce R. Brody, David A. Cox, Eulogio Garcia, Lori L. Grines, Kimberly A. Skelding, Cindy L. Grines. William Beaumont Hospital, Royal Oak, MI

Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen Study.

Low heart rate variability is associated with high risk of sudden death in myocardial infarction patients. This has been attributed to unfavorable autonomic cardiac control. In the present study, the predictive value of heart rate variability for sudden death, mortality from coronary heart disease, and from all causes was investigated in the general population, using brief electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men, aged 40-60 years, were followed and repeatedly examined as part of the Zutphen Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65-85 years, and followed until 1990. Heart rate variability (standard deviation of duration of normal RR intervals) was determined from the resting 12-lead electrocardiogram. The 5-year age-adjusted relative rate of total mortality of men with heart rate variability of < 20 milliseconds (msec) compared with men with heart rate variability of 20-39 msec was 2.1 (95 percent confidence interval 1.4-3.0) in middle-aged men and 1.4 (95% confidence interval 0.9-2.2) in elderly men. Death from noncoronary causes, especially cancer, contributed significantly to this elevated risk. The association of low heart rate variability with sudden death or coronary heart disease mortality was less consistent. In conclusion, in middle-aged men and probably in elderly men, low heart rate variability is predictive of mortality from all causes. This suggests that low heart rate variability is an indicator of compromised health in the general population.

Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.

Heart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men. From 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Age-adjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors. These results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.