Cardiac Monitoring in a Community Hospital—Analysis of 18 Months' Experience

Cardiac monitoring facilities have been present in teaching hospital centers for over five years. A substantial decrease in mortality has been observed in monitored patients with acute myocardial infarction. The community hospital system offers a challenge to effective monitoring since many physicians care for patients and often many kinds of therapy are used.After 18 months of operation mortality from myocardial infarction was only 16.6 percent in a community hospital monitoring unit where the majority of the emergency care and resuscitation was carried out by nurses. Vital to this success was the use of standing orders for nurses, requirement of privilege to practice within the monitoring facility and acceptance of the nurse as a therapist in emergency situations.Fourteen patients were successfully resuscitated and were later discharged from the hospital. Four of them had ventricular fibrillation from digitalis intoxication.Patients with shock and severe congestive heart failure continue to be a major unsolved clinical problem. The results indicate that the potentially viable patient with serious electrical disturbances can almost invariably be salvaged.     

The Circadian Rhythm of Cardiac Frequency in Crayfish: a Multioscillator System?

The aim of this work was to study the humoral regulation of the circadian rhythm of cardiac frequency in crayfish and explore the possibility that isolated heart has a circadian-like oscillation. Sinus glands are the main source of neurohormones in crayfish, and their excision dampens the rhythm, lengthens the period and induces high frequency oscillations. Isolated crayfish hearts show a circadian-like rhythm of frequency with two peaks. These results suggest the participation of several oscillators in the generation and/or expression of the circadian rhythm.     

The Circadian Rhythm of Cardiac Frequency in Crayfish: a Multioscillator System?

The aim of this work was to study the humoral regulation of the circadian rhythm of cardiac frequency in crayfish and explore the possibility that isolated heart has a circadian-like oscillation. Sinus glands are the main source of neurohormones in crayfish, and their excision dampens the rhythm, lengthens the period and induces high frequency oscillations. Isolated crayfish hearts show a circadian-like rhythm of frequency with two peaks. These results suggest the participation of several oscillators in the generation and/or expression of the circadian rhythm.     

Cardiac cell: a biological laser?

We present a new concept of cardiac cells based on an analogy with lasers, practical implementations of quantum resonators. In this concept, each cardiac cell comprises a network of independent nodes, characterised by a set of discrete energy levels and certain transition probabilities between them. Interaction between the nodes is given by threshold-limited energy transfer, leading to quantum-like behaviour of the whole network. We propose that in cardiomyocytes, during each excitation-contraction coupling cycle, stochastic calcium release and the unitary properties of ionic channels constitute an analogue to laser active medium prone to "population inversion" and "spontaneous emission" phenomena. This medium, when powered by an incoming threshold-reaching voltage discharge in the form of an action potential, responds to the calcium influx through L-type calcium channels by stimulated emission of Ca2+ ions in a coherent, synchronised and amplified release process known as calcium-induced calcium release. In parallel, phosphorylation-stimulated molecular amplification in protein cascades adds tuneable features to the cells. In this framework, the heart can be viewed as a coherent network of synchronously firing cardiomyocytes behaving as pulsed laser-like amplifiers, coupled to pulse-generating pacemaker master-oscillators. The concept brings a new viewpoint on cardiac diseases as possible alterations of "cell lasing" properties.     

Cardiac magnetic resonance: a safe procedure?

Cardiac magnetic resonance (CMR) imaging is increasingly used in daily clinical practice. However, its safety and impact on patient management have not been studied in large populations. In a recent online issue of the Journal of the American Cardiology (JACC, August 2009) the EuroCMR (European Cardiovascular Magnetic Resonance) registry evaluated indications, image quality, safety, and impact on patient management of routine CMR imaging in 11,040 patients from 20 European centres (including the VU Medical Centre, Amsterdam, van Rossum).     

Catecholamine and Volume Therapy for Cardiac Surgery in Germany – Results from a Postal Survey

Background

Management of cardiac surgery patients is a very standardized procedure in respective local institutions. Yet only very limited evidence exists concerning optimal indication, safety and efficacy of hemodynamic monitoring catecholamine and fluid therapy.

Methods

Between April and May 2013, all 81 German anaesthesia departments involved in cardiac surgery care were asked to participate in a questionnaire addressing the institutional specific current practice in hemodynamic monitoring, catecholamine and volume therapy.

Results

51 (63%) questionnaires were completed and returned. All participating centers used basic hemodynamic monitoring (i.e. invasive arterial blood pressure and central venous pressure), supplemented by transesophageal echocardiography. Pulmonary arterial catheter and calibrated trend monitoring devices were also routinely available. In contrast, non-calibrated trend monitoring and esophageal doppler ultrasound devices were not commonly in use. Cerebral oximetry is increasingly emerging, but lacks clear indications. The majority of patients undergoing cardiac surgery, especially in university hospitals, required catecholamines during perioperative care, In case of low cardiac output syndrome, dobutamine (32%), epinephrine (30%) or phosphodiesterase inhibitors (8%) were first choice. In case of hypotension following vasoplegia, norepinephrine (96%) represented the most common catecholamine. 88% of the participating centers reported regular use of colloid fluids, with hydroxyethyl starches (HES) being first choice (64%).

Conclusions

Choice of hemodynamic monitoring is homogenous throughout German centers treating cardiac surgery patients. Norepinephrine is the first line catecholamine in cases of decrease in peripheral vascular resistance. However, catecholamine choice for low cardiac output syndrome varies considerably. HES was the primary colloid used for fluid resuscitation. After conduct of this survey, HES use was restricted by European regulatory authorities in critically ill patients and should only be considered as second-line fluid in surgical patients without renal impairment or severe coagulopathy. Large clinical studies addressing catecholamine and fluid therapy in cardiac surgery patients are lacking.     

Cardiac effects of oxytocin: is there a role for this peptide in cardiovascular homeostasis?

Oxytocin is well known for its role in reproduction. However, evidence has emerged suggesting a role in cardiovascular and hydroelectrolytic homeostasis. Although its renal effects have been characterized, the cardiac ones have not been much studied. Therefore, we aimed to investigate the cardiac effects of oxytocin both in vivo and in vitro. In unanesthetized rats (n=6) intravenous oxytocin (1 mug) decreased dP/dt(max) by 15% (P<0.05) and heart rate by 20% (P<0.001), at the first minute after injection. dP/dt(max) was still lower in OT-treated rats than in controls (n=8) after 15 min (P<0.05), while heart rate returned to control values after 5 min. In isolated hearts, oxytocin was able to promote negative inotropic and chronotropic effects. Perfusion with 10(-5), 10(-6) and 10(-7)M oxytocin resulted in approximately 60% (P<0.01), 25% (P<0.01) and 10% (P<0.05) reduction of left ventricle developed pressure, without effect in lower concentrations (10(-10) to 10(-8) M). Also, dP/dt(max) was reduced by 45 and 20% (10(-5) e 10(-6) M; P<0.01), while diastolic pressure raised and heart rate fell only with 10(-5)M oxytocin (P<0.05). Intravenous oxytocin (1 mug; n=6) increased arterial pressure by 22% at the first minute (+23+/-3 mm Hg; P<0.001), returning to control value thereafter. Thus, oxytocin is able to promote directly negative inotropic and chronotropic effects, but its in vivo effect also involves a reflex mechanism, originated from its pressor effect.     

Autoantibodies against the β3-Adrenoceptor Protect from Cardiac Dysfunction in a Rat Model of Pressure Overload

β₃-adrenoceptors (β₃-ARs) mediate a negative inotropic effect in human ventricular cardiomyocytes, which is opposite to that of β₁- and β₂-ARs. It has been previously demonstrated that autoantibodies against the β_1/β₂-AR exist in the sera of some patients with heart failure (HF) and these autoantibodies display agonist-like effects. Our aim in this study was to observe whether autoantibodies against the β₃-AR (β₃-AR Abs) exist in the sera of patients with HF and to assess the effects of β₃-AR Abs on rat model of pressure overload cardiomyopthy. In the present study, the level of β₃-AR Abs in the sera of HF patients was screened by ELISA. β₃-AR Abs from HF patients were administrated to male adult rats with abdominal aortic banding (AAB), and the cardiac function was measured by echocardiographic examination and hemodynamic studies. The biological effects of this autoantibody on cardiomyocytes were evaluated using a motion-edge detection system, intracellular calcium transient assay, and patch clamp techniques. Compared to healthy subjects, the frequency of occurrence and titer of β₃-AR Abs in the sera of HF patients were greatly increased, and β₃-AR Abs could prevent LV dilation and improve the cardiac function of rats with AAB. β₃-AR Abs exhibited negative chronotropic and inotropic effects and were accompanied by a decreased intracellular Ca²⁺ transient and membrane L-type Ca²⁺ current in cardiomyocytes. Our results demonstrated the existence of β₃-AR Abs in the sera of patients with HF and found that this autoantibody could alleviate the cardiac dysfunction induced by pressure-overload in AAB rats.     

Cardiac cells implanted into a cylindrical,vascularized chamber in vivo: pressure generation and morphology

We have previously described a model to implant dissociated cells into a cylindrical, vascularized bed in vivo to promote the formation of functional cardiac muscle constructs. We now investigate the cellular organization and the ability of the constructs to generate intra-luminal pressure. Primary cardiac cells were isolated from hearts of 2–3 day old rats, suspended in fibrin gel and inserted into the lumen of silicone tubing. The silicone tubing was then implanted around the femoral vessels in the groin region of recipient animals. After 3 weeks, the constructs were harvested, placed in an in vitro bath and cannulated via the incorporated femoral artery with a pressure transducer for evaluation of intra-luminal pressure dynamics. Histological evaluation showed the presence of a concentric ring of cardiac cells surrounding the femoral vessels. There was also a significant amount of collagen present around cardiac cells. In addition, we observed a significant amount of neovascularization of the explanted constructs. Electron microscopy showed the presence of longitudinally aligned fibers with a large number of gap junctions. Upon electrical stimulation of a single pulse (7 V, 1.2 ms), the constructs generated an intra-luminal pressure of 1.19 ± 0.45 mmHg (n = 6). In addition, we were able to electrically pace the constructs at frequencies of 0.5–5 Hz. A Starling behavior of the inverse relation between baseline pressure and twitch pressure was observed. Cardiac cells implanted for 3 weeks into the cylindrical vascularized bed formed a tissue construct that demonstrated many of the contractile properties and morphology expected of functioning cardiac tissues.     

Cardiac surgery in patients irradiated for Hodgkin’s lymphoma

Background/Objectives. Therapy for Hodgkin’s lymphoma is disease specific and cannot be compared with treatment for other diseases. It often includes more extensive radiotherapy on the mediastinum than for other malignancies. Cardiac morbidity is known to occur in patients previously irradiated. This study describes the postoperative course after cardiac surgery of patients previously irradiated for Hodgkin’s lymphoma. Methods. From January 1990 until June 2008, 12 patients underwent cardiac surgery in the University Medical Center Utrecht after previous irradiation for Hodgkin’s lymphoma. Data on radiotherapy, surgery and follow-up were collected retrospectively. The postoperative functional status was assessed by a telephone questionnaire. Results. Atrial fibrillation (33%) and pleural effusion (25%) were the most common postoperative complications. After a mean followup of 2.6±2.9 years four patients had died. The remaining patients were all in a favourable New York Heart Association and Canadian Cardiothoracic Society class. The estimated one-, two- and four-year survival rates were 83, 69 and 46% respectively. Conclusion. The early postoperative outcome of cardiac surgery in this population is reasonably good. The long-term results may prove to be disappointing, but the cohort is small. (Neth Heart J 2010;18:61–5.)     

Phosphorylated Phospholamban Stabilizes a Compact Conformation of?the Cardiac Calcium-ATPase

The sarcoendoplasmic reticulum calcium ATPase (SERCA) plays a key role in cardiac calcium handling and is considered a high-value target for the treatment of heart failure. SERCA undergoes conformational changes as it harnesses the chemical energy of ATP for active transport. X-ray crystallography has provided insight into SERCA structural substates, but it is not known how well these static snapshots describe in vivo conformational dynamics. The goals of this work were to quantify the direction and magnitude of SERCA motions as the pump performs work in live cardiac myocytes, and to identify structural determinants of SERCA regulation by phospholamban. We measured intramolecular fluorescence resonance energy transfer (FRET) between fluorescent proteins fused to SERCA cytoplasmic domains. We detected four discrete structural substates for SERCA expressed in cardiac muscle cells. The relative populations of these discrete states oscillated with electrical pacing. Low FRET states were most populated in low Ca (diastole), and were indicative of an open, disordered structure for SERCA in the E2 (Ca-free) enzymatic substate. High FRET states increased with Ca (systole), suggesting rigidly closed conformations for the E1 (Ca-bound) enzymatic substates. Notably, a special compact E1 state was observed after treatment with β-adrenergic agonist or with coexpression of phosphomimetic mutants of phospholamban. The data suggest that SERCA calcium binding induces the pump to undergo a transition from an open, dynamic conformation to a closed, ordered structure. Phosphorylated phospholamban stabilizes a unique conformation of SERCA that is characterized by a compact architecture.     

Cardiac natriuretic peptides: a physiological lineage of cardioprotective hormones?

Vertebrate hearts from fish to mammals secrete peptide hormones with profound natriuretic, diuretic, and vasodilatory activity; however, the specific role of these cardiac natriuretic peptides (NPs) in homeostasis is unclear. NPs have been suggested to be involved in salt excretion in saltwater teleosts, whereas they are proposed to be more important in volume regulation in mammals. In this review, we consider an alternative (or perhaps complementary) function of NPs to protect the heart. This hypothesis is based on a number of observations. First, evidence for NPs, or NP-like activity has been found in all vertebrate hearts thus far examined, from osmoconforming saltwater hagfish to euryhaline freshwater and saltwater teleosts to terrestrial mammals. Thus the presence of cardiac NPs appears to be independent of environmental conditions that may variously affect salt and water balance. Second, cardiac stretch is a universal, and one of the most powerful, NP secretagogues. Furthermore, stretch-induced NP release in euryhaline teleosts appears relatively independent of ambient salinity. Third, excessive cardiac stretch that increases end-diastolic volume (EDV) can compromise the mechanical ability of the heart by decreasing actin-myosin interaction (length-tension) or through Laplace effects whereby as EDV increases, the wall tension necessary to maintain a constant pressure must also increase. Excessive cardiac stretch can be produced by factors that decrease cardiac emptying (i.e., increased arterial pressure), or by factors that increase cardiac filling (i.e., increased blood volume, increased venous tone, or decreased venous compliance). Fourth, the major physiological actions of cardiac NPs enhance cardiac emptying and decrease cardiac filling. In fish, NPs promote cardiac emptying by decreasing gill vascular resistance, thereby lowering ventral aortic pressure. In mammals a similar effect is achieved through pulmonary vasodilation. NPs also decrease cardiac filling by decreasing blood volume and increasing venous compliance, the latter producing a rapid fall in central venous pressure. Fifth, the presence of NP clearance receptors in the gill and lung (between the heart and systemic circulation) suggest that these tissues may be exposed to considerably higher NP titers than are systemic tissues. Thus, a decrease in outflow resistance immediately downstream from the heart may be the first response to increased cardiac distension. Because the physiology of cardiac NPs is basically the same in fish and mammals, we propose that the cardioprotective effects of NPs have been well preserved throughout the course of vertebrate evolution. It is also likely that the cardioprotective role of NPs was one of the most primordial homeostatic activities of these peptides in the earliest vertebrates.     

Cardiac troponins predict adverse clinical outcomes in stable coronary artery disease: a dose–response meta-analysis of prospective studies

Background: Predictive value of cardiac tropnins (cTns) in stable coronary artery disease (SCAD) has not been fully investigated.

Methods: We performed a meta-analysis to evaluate the dose–response relationship between serum detectable/rising cTns and adverse clinical outcomes, including all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), heart failure (HF) or major adverse cardiovascular events (MACEs) in SCAD.

Results: Sixteen studies involved 34,854 subjects were included. Compared with patients with negative/undetectable cTns, those with rising/detectable cTns were associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs [the hazard ratio (HR) was 1.83 (95% confidence interval (CI) 1.61–2.08), 2.11 (1.80–2.48), 1.43 (1.26–1.62), 2.36 (1.97–2.83) and 1.99 (1.57–2.53), respectively]. Dose–response analysis have revealed that per 1-SD increment of cTnT was associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs [the HR was 1.78 (1.20–2.63), 1.62 (1.41–1.85), 1.26 (1.12–1.42), 1.78 (1.17–2.69) and 1.26 (1.00–1.59), respectively].

Conclusion: Rising/detectable cTns was associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs in SCAD in a dose–response manner.     

Cardiac Effects of Antiretroviral-Na?ve versus Antiretroviral-Exposed HIV Infection in Children

Background

Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown.

Methods

This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values.

Results

Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children.

Conclusions

ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter and higher mass, but less functional impairment.     

SERUM TRANSAMINASE—A Test to Aid in Diagnosis of Cardiac Infarction

Within 24 hours following myocardial infarction there is a pronounced increase in the level of the enzyme glutamic-oxalacetic transaminase found in the serum. This enzyme can be detected in serum by a rapid and convenient procedure. An increase in the level of serum transaminase is typical of only a few pathological conditions all of which can readily be distinguished from myocardial infarction by other methods.     

An Adenylyl Cyclase-mAKAP�� Signaling Complex Regulates cAMP Levels in Cardiac Myocytes

Protein kinase A-anchoring proteins (AKAPs) play important roles in the compartmentation of cAMP signaling, anchoring protein kinase A (PKA) to specific cellular organelles and serving as scaffolds that assemble localized signaling cascades. Although AKAPs have been recently shown to bind adenylyl cyclase (AC), the functional significance of this association has not been studied. In cardiac myocytes, the muscle protein kinase A-anchoring protein β (mAKAPβ) coordinates cAMP-dependent, calcium, and MAP kinase pathways and is important for cellular hypertrophy. We now show that mAKAPβ selectively binds type 5 AC in the heart and that mAKAPβ-associated AC activity is absent in AC5 knock-out hearts. Consistent with its known inhibition by PKA phosphorylation, AC5 is inhibited by association with mAKAPβ-PKA complexes. AC5 binds to a unique N-terminal site on mAKAP-(245–340), and expression of this peptide disrupts endogenous mAKAPβ-AC association. Accordingly, disruption of mAKAPβ-AC5 complexes in neonatal cardiac myocytes results in increased cAMP and hypertrophy in the absence of agonist stimulation. Taken together, these results show that the association of AC5 with the mAKAPβ complex is required for the regulation of cAMP second messenger controlling cardiac myocyte hypertrophy.The formation of multimolecular protein complexes contributes to the specificity of intracellular signaling pathways, including those regulating cardiac myocyte hypertrophy. The cAMP-dependent protein kinase (PKA)³ is targeted to specific intracellular domains by protein kinase A-anchoring proteins (AKAPs) that often serve as scaffolding proteins for diverse signaling enzymes (1). In the heart, global disruption of PKA anchoring affects cardiac contractility, while the inhibited expression of individual AKAPs such as mAKAPβ or AKAP-Lbc attenuates adrenergic-induced hypertrophy of cultured neonatal myocytes (2–4). We have recently shown that specific AKAPs, namely AKAP79 and Yotiao, bind adenylyl cyclases (AC) (5, 6). However, the functional significance of AC-AKAP complexes has not been demonstrated.mAKAPβ, expressed in striated myocytes, is one of two known splice variants encoded by the single mAKAP (AKAP6) gene (7). We previously published that mAKAPβ is primarily localized to the outer membrane of the nuclear envelope via direct binding to nesprin-1α (4, 8). In cardiac myocytes, mAKAPβ serves as the scaffold for a multimolecular signaling complex that in addition to PKA includes the ryanodine receptor (RyR2), the protein phosphatases PP2A and calcineurin, phosphodiesterase 4D3 (PDE4D3), exchange protein activated by cAMP (Epac1), ERK5, and MEK5 mitogen-activated protein kinases, molecules implicated in the regulation of cardiac hypertrophy (4, 7–13). mAKAPβ complexes facilitate cross-talk between MAP kinase, calcium, and cAMP signaling pathways, permitting feedback inhibition of cAMP levels and the dynamic regulation of PKA and ERK5 activity (4, 9–13). Accordingly, mAKAPβ RNAi attenuates adrenergic and cytokine-induced hypertrophy of cultured rat neonatal ventricular myocytes (4, 11).Because mAKAPβ forms a complex with two cAMP effectors and a metabolizing enzyme for cAMP, we considered whether AC might also be an integral part of the mAKAPβ complex. We now demonstrate that type 5 adenylyl cyclase (AC5) binds directly a unique N-terminal site on mAKAPβ and is the predominant AC isoform associated with mAKAPβ in the heart. We show that AC5 bound to mAKAPβ is inhibited by PKA-dependent negative feedback. Importantly, inhibition of endogenous mAKAPβ-AC5 binding revealed the functional importance of these complexes for the regulation of cAMP-dependent myocyte hypertrophy.