Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction

Background: Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. Methods and Results: Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-alpha mRNA, and Ca2+ handling proteins were measured. MI area was reduced in TDI (21 +/- 4%) compared with SDI (38 +/- 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca2+ handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. Conclusions: ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI. (J Cardiac Fail 2012; 18:734-744)

Sudden Cardiac Death in Brazil: Study Based on Physicians' Perceptions of the Public Health Care System

Background: There are no available statistical data about sudden cardiac death in Brazil. Therefore, this study has been conducted to evaluate the incidence of sudden cardiac death in our population and its implications. Methods: The research methodology was based on Thurstone's Law of Comparative Judgment, whose premise is that the more an A stimulus differs from a B stimulus, the greater will be the number of people who will perceive this difference. This technique allows an estimation of actual occurrences from subjective perceptions, when compared to official statistics. Data were collected through telephone interviews conducted with Primary and Secondary Care physicians of the Public Health Service in the Metropolitan Area of Sao Paulo (MASP). Results: In the period from October 19, 2009, to October 28, 2009, 196 interviews were conducted. The incidence of 21,270 cases of sudden cardiac death per year was estimated by linear regression analysis of the physicians responses and data from the Mortality Information System of the Brazilian Ministry of Health, with the following correlation and determination coefficients: r = 0.98 and r2= 0.95 (95% confidence interval 0.81.0, P < 0.05). The lack of waiting list for specialized care and socioadministrative problems were considered the main barriers to tertiary care access. Conclusions: The incidence of sudden cardiac death in the MASP is high, and it was estimated as being higher than all other causes of deaths; the extrapolation technique based on the physicians perceptions was validated; and the most important bureaucratic barriers to patient referral to tertiary care have been identified. (PACE 2012; 35:13261331)

Global and Regional Ventricular Repolarization Study by Body Surface Potential Mapping in Patients with Left Bundle-Branch Block and Heart Failure Undergoing Cardiac Resynchronization Therapy

Background: The controversial effects promoted by cardiac resynchronization therapy (CRT) on the ventricular repolarization (VR) have motivated VR evaluation by body surface potential mapping (BSPM) in CRT patients. Methods: Fifty-two CRT patients, mean age 58.8 +/- 12.3 years, 31 male, LVEF 27.5 +/- 9.2, NYHA III-IV heart failure with QRS181.5 +/- 14.2 ms, underwent 87-lead BSPM in sinus rhythm (BASELINE) and biventricular pacing (BIV). Measurements of mean and corrected QT intervals and dispersion, mean and corrected T peak end intervals and their dispersion, and JT intervals characterized global and regional (RV, Intermediate, and LV regions) ventricular repolarization response. Results: Global QTm (P < 0.001) and QTcm (P < 0.05) were decreased in BIV; QTm was similar across regions in both modes (P = ns); QTcm values were lower in RV/LV than in Intermediate region in BASELINE and BIV (P < 0.001); only RV/Septum showed a significant difference (P < 0.01) in the BIV mode. QTD values both of BASELINE (P < 0.01) and BIV (P < 0.001) were greater in the Intermediate than in the LV region. CRT effect significantly reduced global/regional QTm and QTcm values. QTD was globally decreased in RV/LV (Intermediate: P = ns). BIV mode significantly reduced global T peak end mean and corrected intervals and their dispersion. JT values were not significant. Conclusions: Ventricular repolarization parameters QTm, QTcm, and QTD global/regional values, as assessed by BSPM, were reduced in patients under CRT with severe HF and LBBB. Greater recovery impairment in the Intermediate region was detected by the smaller variation of its dispersion.

Cardiac and pulmonary arterial remodeling after sinoaortic denervation in normotensive rats

Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end-organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n = 8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (alpha-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11 +/- 0.49 vs. 5 +/- 0.3 mm Hg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8 +/- 0.26 vs. 5.02 +/- 0.21 mm Hg) and RV (5.1 +/- 0.21 vs. 4.2 +/- 0.12 mm Hg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (similar to 6-fold) and III (similar to 5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased a-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage. (C) 2011 Elsevier B.V. All rights reserved.

Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia

Abstract Introduction We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI). Methods Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test. Results FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM. Conclusions Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.

Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing ventilator-associated pneumonia after cardiac surgery: an observational study

Abstract Background The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery. Methods This was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1. Results Thirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29). Conclusion Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.

Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction

BACKGROUND: Ischemia and reperfusion (IR) injury remains a major cause of morbidity and mortality and multiple molecular and cellular pathways have been implicated in this injury. We determined whether acute inhibition of excessive mitochondrial fission at the onset of reperfusion improves mitochondrial dysfunction and cardiac contractility postmyocardial infarction in rats. METHODS AND RESULTS: We used a selective inhibitor of the fission machinery, P110, which we have recently designed. P110 treatment inhibited the interaction of fission proteins Fis1/Drp1, decreased mitochondrial fission, and improved bioenergetics in three different rat models of IR, including primary cardiomyocytes, ex vivo heart model, and an in vivo myocardial infarction model. Drp1 transiently bound to the mitochondria following IR injury and P110 treatment blocked this Drp1 mitochondrial association. Compared with control treatment, P110 (1 μmol/L) decreased infarct size by 28 ± 2% and increased adenosine triphosphate levels by 70+1% after IR relative to control IR in the ex vivo model. Intraperitoneal injection of P110 (0.5 mg/kg) at the onset of reperfusion in an in vivo model resulted in improved mitochondrial oxygen consumption by 68% when measured 3 weeks after ischemic injury, improved cardiac fractional shortening by 35%, reduced mitochondrial H2O2 uncoupling state by 70%, and improved overall mitochondrial functions. CONCLUSIONS: Together, we show that excessive mitochondrial fission at reperfusion contributes to long-term cardiac dysfunction in rats and that acute inhibition of excessive mitochondrial fission at the onset of reperfusion is sufficient to result in long-term benefits as evidenced by inhibiting cardiac dysfunction 3 weeks after acute myocardial infarction.

The impact of cardiac rehabilitation on lifestyles, psychological correlates and the clinical course of cardiac disease

Objectives: The aim of this research was to evaluate the impact of Cardiac Rehabilitation (CR) on risky lifestyles, quality of life, psychopathology, psychological distress and well-being, considering the potential moderating role of depression, anxiety and psychosomatic syndromes on lifestyles modification. The influence of CR on cardiac morbidity and mortality was also evaluated. Methods: The experimental group (N=108), undergoing CR, was compared to a control group (N=85) of patients affected by cardiovascular diseases, not undergoing CR, at baseline and at 1-month, 6- and 12-months follow-ups. The assessment included: the Structured Clinical Interview for DSM-IV, the structured interview based on Diagnostic Criteria for Psychosomatic Research (DCPR), GOSPEL questionnaire on lifestyles, Pittsburgh Sleep Quality Index, Morisky Medication Adherence Scale, MOS 36-Item Short Form Health Survey, Symptom Questionnaire, Psychological Well-Being Scale and 14-items Type D Scale. Results: Compared to the control group, CR was associated to: maintenance of the level of physical activity, improvement of correct dietary behaviors and stress management, enhancement of quality of life and sleep; reduction of the most frequently observed psychiatric diagnoses and psychosomatic syndromes at baseline. On the contrary, CR was not found to be associated with: healthy dietary habits, weight loss and improvement on medications adherence. In addition, there were no relevant effects on sub-clinical psychological distress and well-being, except for personal growth and purpose in life (PWB). Also, CR did not seem to play a protective role against cardiac recurrences. The presence of psychosomatic syndromes and depressive disorders was a mediating factor on the modification of specific lifestyles. Conclusions: The findings highlight the need of a psychosomatic assessment and an evaluation of psychological sub-clinical symptomatology in cardiac rehabilitation, in order to identify and address specific factors potentially associated with the clinical course of the heart disease.

Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa

Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up.

Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR) to cardiovascular health outcomes. Secondary prevention through exercise-based CR is the intervention with the best scientific evidence to contribute to decrease morbidity and mortality in coronary artery disease, in particular after myocardial infarction but also incorporating cardiac interventions and chronic stable heart failure. The present position paper aims to provide the practical recommendations on the core components and goals of CR intervention in different cardiovascular conditions, to assist in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of CR. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, national or individual centre level, need to consider where and how structured programmes of CR can be delivered to all patients eligible. Thus a novel, disease-oriented document has been generated, where all components of CR for cardiovascular conditions have been revised, presenting both well-established and controversial aspects. A general table applicable to all cardiovascular conditions and specific tables for each clinical disease have been created and commented.

Early non-invasive cardiac output monitoring in hemodynamically unstable intensive care patients: A multi-center randomized controlled trial

Introduction Acute hemodynamic instability increases morbidity and mortality. We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome. Methods A multicenter, randomized controlled trial was conducted in three European university hospital intensive care units in 2006 and 2007. A total of 388 hemodynamically unstable patients identified during their first six hours in the intensive care unit (ICU) were randomized to receive either non-invasive cardiac output monitoring for 24 hrs (minimally invasive cardiac output/MICO group; n = 201) or usual care (control group; n = 187). The main outcome measure was the proportion of patients achieving hemodynamic stability within six hours of starting the study. Results The number of hemodynamic instability criteria at baseline (MICO group mean 2.0 (SD 1.0), control group 1.8 (1.0); P = .06) and severity of illness (SAPS II score; MICO group 48 (18), control group 48 (15); P = .86)) were similar. At 6 hrs, 45 patients (22%) in the MICO group and 52 patients (28%) in the control group were hemodynamically stable (mean difference 5%; 95% confidence interval of the difference -3 to 14%; P = .24). Hemodynamic support with fluids and vasoactive drugs, and pulmonary artery catheter use (MICO group: 19%, control group: 26%; P = .11) were similar in the two groups. The median length of ICU stay was 2.0 (interquartile range 1.2 to 4.6) days in the MICO group and 2.5 (1.1 to 5.0) days in the control group (P = .38). The hospital mortality was 26% in the MICO group and 21% in the control group (P = .34). Conclusions Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU, nor does it alter the hemodynamic support or outcome. Our results emphasize the need to evaluate technologies used to measure stroke volume and cardiac output--especially their impact on the process of care--before any large-scale outcome studies are attempted.

All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study

Objective To examine all cause and disease specific mortality in patients with osteoarthritis of the knee or hip. Design Population based cohort study. Setting General practices in the southwest of England. Participants 1163 patients aged 35 years or over with symptoms and radiological confirmation of osteoarthritis of the knee or hip. Main outcome measures Age and sex standardised mortality ratios and multivariable hazard ratios of death after a median of 14 years’ follow-up. Results Patients with osteoarthritis had excess all cause mortality compared with the general population (standardised mortality ratio 1.55, 95% confidence interval 1.41 to 1.70). Excess mortality was observed for all disease specific causes of death but was particularly pronounced for cardiovascular (standardised mortality ratio 1.71, 1.49 to 1.98) and dementia associated mortality (1.99, 1.22 to 3.25). Mortality increased with increasing age (P for trend <0.001), male sex (adjusted hazard ratio 1.59, 1.30 to 1.96), self reported history of diabetes (1.95, 1.31 to 2.90), cancer (2.28, 1.50 to 3.47), cardiovascular disease (1.38, 1.12 to 1.71), and walking disability (1.48, 1.17 to 1.86). However, little evidence existed for increased mortality associated with previous joint replacement, obesity, depression, chronic inflammatory disease, eye disease, or presence of pain at baseline. The more severe the walking disability, the higher was the risk of death (P for trend <0.001). Conclusion Patients with osteoarthritis are at higher risk of death compared with the general population. History of diabetes, cancer, or cardiovascular disease and the presence of walking disability are major risk factors. Management of patients with osteoarthritis and walking disability should focus on effective treatment of cardiovascular risk factors and comorbidities, as well as on increasing physical activity.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index. The SWIss Venous ThromboEmbolism Registry (SWIVTER)

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study

PURPOSE: To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure. METHODS: The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h. RESULTS: Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8-57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08-2.77; p = 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1-1.01; p = 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p < 0.001) and mechanical ventilation (p < 0.001) for longer and had longer intensive care unit stays (p < 0.001) and greater mortality (25.9 vs. 1.7 %; p < 0.001) than patients who did not. CONCLUSIONS: Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.

Early reperfusion hemodynamics predict recovery in rat hearts: a potential approach towards evaluating cardiac grafts from non-heart-beating donors

Aims Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. Methods and Results Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *103 mmHg*beats*min−1 (p<0.01). Conclusion Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.