Venkata Krishna Puppala

The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia

INTRODUCTION Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH<7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors. METHODS A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH<7.2 and pH≥7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome. RESULTS Sixty-two percent of shockable CA patients with pH≥7.20 had good neurological outcome as compared to 34% patients with pH<7.20. Shockable CA patients with pH≥7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p=0.013, OR 3.3, 95% CI (1.28-8.45)]. In comparison, non-shockable CA patients with p≥7.20 did not have a significantly different neurological outcome as compared to those with pH<7.20 [p=0.97, OR 1.02, 95% CI (0.31-3.3)]. CONCLUSION Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors.

Modulation of the autonomic nervous system assessed through heart rate variability by a mindfulness based stress reduction program

Heart rate variability (HRV) is an established method to evaluate cardiac sympatho-vagal balance [1]. Reduced HRV is an adverse prognostic marker for fatal arrhythmias in myocardial infarction and heart failure patients [2,3]. Mindfulness based stress reduction (MBSR) is a well-delineated 8-week meditation program that has a standardized technique [4]. Certain meditation practices have been shown to positively influence HRV [5,6], but the effects of MBSR on HRV have not been established. Twenty two healthy volunteerswere recruited fromparticipants of a MBSR program. After excluding for followup loss and ECG artifact, final study population was 18 subjects (44% men, mean age 52.7 ± 11.8 years, mean BMI 24.0 ± 3.9 kg/m). The study protocol was approved by the University of Minnesota Institutional Review Board, and written informed consent (in accordancewith theHelsinki Declaration) was obtained. Volunteers were reimbursed US

Syncope: Classification and risk stratification

50 per visit to cover travel costs. MBSR consists of an 8-week intervention with weekly classes that last 2–3 h, and daily home practice is encouraged [7].

Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study.

BACKGROUND Syncope is one of the most common reasons for emergency department and urgent care clinic visits. The management of syncope continues to be a challenging problem for front-line providers inasmuch as there are a multitude of possible causes for syncope ranging from relatively benign conditions to potentially life-threatening ones. In any event, it is important to identify those syncope patients who are at immediate risk of life-threatening events; these individuals require prompt hospitalization and thorough evaluation. Conversely, it is equally important to avoid unnecessary hospitalization of low-risk patients since unneeded hospital care adds to the healthcare cost burden. RESULTS Historically, front-line providers have taken a conservative approach with admission rates as high as 30-50% among syncope patients. A number of studies evaluating both the short- and long-term risk of adverse events in patients with syncope have focused on development of risk-stratification guidelines to assist providers in making a confident and well-informed choice between hospitalization and out-patient referral. In this regard, a much needed consensus on optimal decision-making process has not been developed to date. However, knowledge from various available risk-stratification studies can be helpful. CONCLUSION This review summarizes the findings of various risk-stratification studies and points out key differences between them. While, the existing risk-stratification methods cannot replace critical assessment by an experienced physician, they do provide valuable guidance. In addition, the various risk-assessment schemes highlight the need for careful initial clinical assessment of syncope patients, selective testing, and being mindful of the short- and long-term risks.

Dynamin-related protein 1 mediates low glucose-induced endothelial dysfunction in human arterioles

Objective Co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension than patients with OSA or COPD alone. Studies showed that elderly patients with OSA alone do not have increased risk of atrial fibrillation (AF) but it is not known if overlap patients have higher risk of AF. To determine whether elderly patients with overlap syndrome have an increased risk of AF. Methods In this single center, community-based retrospective cohort analysis, data were collected on 2,873 patients > 65 years of age without AF, presenting in the year 2006. Patients were divided into OSA group (n = 60), COPD group (n = 416), overlap syndrome group (n = 28) and group with no OSA or COPD (n = 2369). The primary endpoint was incidence of new-onset AF over the following two years. Logistic regression was performed to adjust for heart failure (HF), coronary artery disease, hypertension (HTN), cerebrovascular disease, cardiac valve disorders, diabetes mellitus, hyperlipidemia, chronic kidney disease (CKD) and obesity. Results The incidence of AF was 10% in COPD group, 6% in OSA group and 21% in overlap syndrome group (P < 0.05). After adjusting for age, sex, HF, CKD, and HTN, patients with overlap syndrome demonstrated a significant association with new-onset AF (OR = 3.66, P = 0.007). HF, CKD and HTN were also significantly associated with new-onset AF (P < 0.05). Conclusion Among elderly patients, the presence of overlap syndrome is associated with a marked increase in risk of new-onset AF as compared to the presence of OSA or COPD alone.

Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy

Intensive glycemic regulation has resulted in an increased incidence of hypoglycemia. Hypoglycemic burden correlates with adverse cardiovascular complications and contributes acutely and chronically to endothelial dysfunction. Prior data indicate that mitochondrial dysfunction contributes to hypoglycemia-induced endothelial dysfunction, but the mechanisms behind this linkage remain unknown. We attempt to determine whether clinically relevant low-glucose (LG) exposures acutely induce endothelial dysfunction through activation of the mitochondrial fission process. Characterization of mitochondrial morphology was carried out in cultured endothelial cells by using confocal microscopy. Isolated human arterioles were used to explore the effect LG-induced mitochondrial fission has on the formation of detrimental reactive oxygen species (ROS), bioavailability of nitric oxide (NO), and endothelial-dependent vascular relaxation. Fluorescence microscopy was employed to visualize changes in mitochondrial ROS and NO levels and videomicroscopy applied to measure vasodilation response. Pharmacological disruption of the profission protein Drp1 with Mdivi-1 during LG exposure reduced mitochondrial fragmentation among vascular endothelial cells (LG: 0.469; LG+Mdivi-1: 0.276; P = 0.003), prevented formation of vascular ROS (LG: 2.036; LG+Mdivi-1: 1.774; P = 0.005), increased the presence of NO (LG: 1.352; LG+Mdivi-1: 1.502; P = 0.048), and improved vascular dilation response to acetylcholine (LG: 31.6%; LG+Mdivi-1; 78.5% at maximum dose; P < 0.001). Additionally, decreased expression of Drp1 via siRNA knockdown during LG conditions also improved vascular relaxation. Exposure to LG imparts endothelial dysfunction coupled with altered mitochondrial phenotypes among isolated human arterioles. Disruption of Drp1 and subsequent mitochondrial fragmentation events prevents impaired vascular dilation, restores mitochondrial phenotype, and implicates mitochondrial fission as a primary mediator of LG-induced endothelial dysfunction.NEW & NOTEWORTHY Acute low-glucose exposure induces mitochondrial fragmentation in endothelial cells via Drp1 and is associated with impaired endothelial function in human arterioles. Targeting of Drp1 prevents fragmentation, improves vasofunction, and may provide a therapeutic target for improving cardiovascular complications among diabetics.Listen to this articles corresponding podcast @ http://ajpheart.podbean.com/e/mitochondrial-dynamics-impact-endothelial-function/.

Risk Stratification of Patients Presenting with Transient Loss of Consciousness

Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day). Each treatment period was 8 weeks long separated by 4 weeks of washout. Endothelial function and plasma markers of endothelial activation (intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)) were measured prior to and 2 hours following acute dosing of sitagliptin or placebo, as well as following 8 weeks of intervention with each pill. Thirty subjects completed the study and were included in analyses. Neither acute nor chronic sitagliptin therapy resulted in significant changes in vascular endothelial function. While post-acute sitagliptin ICAM-1 levels were lower than that post-chronic sitagliptin, the ICAM-1 concentration was not significantly different than pre-acute sitagliptin levels or levels measured in relationship to placebo. There were no significant changes in plasma VCAM-1 levels at any time point. Acute and chronic sitagliptin therapies have neutral effects on the vascular endothelium in the setting of metformin background therapy. In conclusion, our findings suggest DPP-4 inhibition has a neutral effect on cardiovascular risk in patients without a history of heart failure or renal insufficiency. Trial Registration: NCT01859793

Blunted Chronotropic Response to Hypotension in Cough Syncope

Important goals in the initial evaluation of patients with transient loss of consciousness include determining whether the episode was syncope and choosing the venue for subsequent care. Patients who have high short-term risk of adverse outcomes need prompt hospitalization for diagnosis and/or treatment, whereas others may be safely referred for outpatient evaluation. This article summarizes the most important available risk assessment studies and points out key differences among the existing recommendations. Current risk stratification methods cannot replace critical assessment by an experienced physician, but they do provide much needed guidance and offer direction for future risk stratification consensus development.