Does heart rate variability correlate with long-term prognosis in myocardial infarction patients treated by early revascularization?

AIMTo assess the prevalence of depressed heart rate variability (HRV) after an acute myocardial infarction (MI), and to evaluate its prognostic significance in the present era of immediate reperfusion.METHODSTime-domain HRV (obtained from 24-h Holter recordings) was assessed in 326 patients (63.5 ± 12.1 years old; 80% males), two weeks after a complicated MI treated by early reperfusion: 208 ST-elevation myocardial infarction (STEMI) patients (in which reperfusion was successfully obtained within 6 h of symptoms in 94% of cases) and 118 non-ST-elevation myocardial infarction (NSTEMI) patients (percutaneous coronary intervention was performed within 24 h and successful in 73% of cases). Follow-up of the patients was performed via telephone interviews a median of 25 mo after the index event (95%CI of the mean 23.3-28.0). Primary end-point was occurrence of all-cause or cardiac death; secondary end-point was occurrence of major clinical events (MCE, defined as mortality or readmission for new MI, new revascularization, episodes of heart failure or stroke). Possible correlations between HRV parameters (mainly the standard deviation of all normal RR intervals, SDNN), clinical features (age, sex, type of MI, history of diabetes, left ventricle ejection fraction), angiographic characteristics (number of coronary arteries with critical stenoses, success and completeness of revascularization) and long-term outcomes were analysed.RESULTSMarkedly depressed HRV parameters were present in a relatively small percentage of patients: SDNN < 70 ms was found in 16% and SDNN < 50 ms in 4% of cases. No significant differences were present between STEMI and NSTEMI cases as regards to their distribution among quartiles of SDNN (χ2 =1.536, P = 0.674). Female sex and history of diabetes maintained a significant correlation with lower values of SDNN at multivariate Cox regression analysis (respectively: P = 0.008 and P = 0.008), while no correlation was found between depressed SDNN and history of previous MI (P = 0.999) or number of diseased coronary arteries (P = 0.428) or unsuccessful percutaneous coronary intervention (PCI) (P = 0.691). Patients with left ventricle ejection fraction (LVEF) < 40% presented more often SDNN values in the lowest quartile (P < 0.001). After > 2 years from infarction, a total of 10 patients (3.1%) were lost to follow-up. Overall incidence of MCE at follow-up was similar between STEMI and NSTEMI (P = 0.141), although all-cause and cardiac mortality were higher among NSTEMI cases (respectively: 14% vs 2%, P = 0.001; and 10% vs 1.5%, P = 0.001). The Kaplan-Meier survival curves for all-cause mortality and for cardiac deaths did not reveal significant differences between patients with SDNN in the lowest quartile and other quartiles of SDNN (respectively: P = 0.137 and P = 0.527). Also the MCE-free survival curves were similar between the group of patients with SDNN in the lowest quartile vs the patients of the other SDNN quartiles (P = 0.540), with no difference for STEMI (P = 0.180) or NSTEMI patients (P = 0.541). By the contrary, events-free survival was worse if patients presented with LVEF < 40% (P = 0.001).CONCLUSIONIn our group of patients with a recent complicated MI, abnormal autonomic parameters have been found with a prevalence that was similar for STEMI and NSTEMI cases, and substantially unchanged in comparison to what reported in the pre-primary-PCI era. Long-term outcomes did not correlate with level of depression of HRV parameters recorded in the subacute phase of the disease, both in STEMI and in NSTEMI patients. These results support lack of prognostic significance of traditional HRV parameters when immediate coronary reperfusion is utilised.

Screening of unknown atrial fibrillation through handheld device in the elderly

Objective To estimate the prevalence of unknown atrial fibrillation(AF)in the elderly population of the Veneto Region,Italy.Methods 1820 patients aged≥65 years with no history of AF and not anticoagulated were enrolled in primary-care settings.They underwent an opportunistic electrocardiogram screening with a handheld device(My Diagnostick)designed to specifically detect AF.The electrocardiogram recordings were reviewed by the researchers,who confirmed the presence of AF.Results The device detected an arrhythmia in 143 patients,which was confirmed as AF in 101/143(70.6%),with an overall prevalence of AF of 5.5%(101/1820).Prevalence of unknown AF resulted in 3.6%in patients aged 65–74 years,and 7.5%in patients age 75 or older,and increased according to CHA2 DS2-VASc score:3.5%in patients with a score of 1 or 2,5.6%in patients with a score of 3,7.0%in patients with a score of 4,and 7.2%in patients with a score≥5.The detection rate was significantly higher in patients with mild symptoms compared to asymptomatic counterparts(24.1%vs.4.0%,P<0.0001).At multivariate analysis,congestive heart failure and age≥75 years-old were independent predictors for screen-detected AF.Conclusions An opportunistic screening with handheld device revealed an unexpectedly high prevalence of unknown AF in elderly patients with mild symptoms.Prevalence increased with age and CHA2DS2-VASc score.

Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications

Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.

Cellular and subcellular coherent dynamics,biological functional properties,and system-environment interaction

In this view point paper,we briefly summarize some of the clinical,biochemical and biophysical results obtained in our research on Relaxation Response.We also qualitatively describe the theoretical biophysical model that could link them.Our work points to a unified view of the human biological system activity,joining the dynamics ruling the interactions and correlations of the microscopic components to the knowledge of their specific individual properties in the effort of going beyond a purely atomistic approach.

Role of T Cells in Viral and Immune-mediated Myocarditis

Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experimental models are used to mimic myocarditis in humans. Here, coxsackie virus B3-induced and non-virus-induced myocarditis models and data obtained in clinical studies were reviewed. Experimental murine myocarditis following immunization with α-myosin together with complete Freund adjuvant represents the classical immune-mediated model. T helper 1 (Th1) and Th2 pathways and important cytokines are involved in the autoimmunity of myocarditis, and the dynamic balance between Th17 and regulatory T cell seems to have an important role in the process of myocarditis. The purpose of this review is to summarize the existing understanding of the immunological mechanisms underlying myocarditis and exploring gaps in knowledge in both animal and human studies, since these mechanistic insights are a critical requirement for the development of novel therapeutic and vaccination strategies.