Modeling left ventricular diastolic dysfunction: classification and key indicators.

BACKGROUND: Mathematical modeling can be employed to overcome the practical difficulty of isolating the mechanisms responsible for clinical heart failure in the setting of normal left ventricular ejection fraction (HFNEF). In a human cardiovascular respiratory system (H-CRS) model we introduce three cases of left ventricular diastolic dysfunction (LVDD): (1) impaired left ventricular active relaxation (IR-type); (2) increased passive stiffness (restrictive or R-type); and (3) the combination of both (pseudo-normal or PN-type), to produce HFNEF. The effects of increasing systolic contractility are also considered. Model results showing ensuing heart failure and mechanisms involved are reported. METHODS: We employ our previously described H-CRS model with modified pulmonary compliances to better mimic normal pulmonary blood distribution. IR-type is modeled by changing the activation function of the left ventricle (LV), and R-type by increasing diastolic stiffness of the LV wall and septum. A 5th-order Cash-Karp Runge-Kutta numerical integration method solves the model differential equations. RESULTS: IR-type and R-type decrease LV stroke volume, cardiac output, ejection fraction (EF), and mean systemic arterial pressure. Heart rate, pulmonary pressures, pulmonary volumes, and pulmonary and systemic arterial-venous O2 and CO2 differences increase. IR-type decreases, but R-type increases the mitral E/A ratio. PN-type produces the well-described, pseudo-normal mitral inflow pattern. All three types of LVDD reduce right ventricular (RV) and LV EF, but the latter remains normal or near normal. Simulations show reduced EF is partly restored by an accompanying increase in systolic stiffness, a compensatory mechanism that may lead clinicians to miss the presence of HF if they only consider LVEF and other indices of LV function. Simulations using the H-CRS model indicate that changes in RV function might well be diagnostic. This study also highlights the importance of septal mechanics in LVDD. CONCLUSION: The model demonstrates that abnormal LV diastolic performance alone can result in decreased LV and RV systolic performance, not previously appreciated, and contribute to the clinical syndrome of HF. Furthermore, alterations of RV diastolic performance are present and may be a hallmark of LV diastolic parameter changes that can be used for better clinical recognition of LV diastolic heart disease.

Syncope, seizure, or both? An unusual case of complete heart block.

Syncope and epileptic seizures have common presenting features that make it difficult to determine if a patient's collapse is primarily cardiac or neurologic. The distinction is blurred further if epileptic neural activity provokes cardiac arrhythmias known to cause syncope. We present a case of convulsive movements, progressive atrioventricular block, and syncope in a patient known to have epilepsy. The history, serial electrocardiographic tracings, and other diagnostic tests strongly suggest the ictal bradycardia syndrome. The case illustrates interesting aspects of central autonomic function and the diagnostic and therapeutic dilemmas of evaluating and treating patients who present with this problem.

Medical qualification of a commercial spaceflight participant: not your average astronaut.

BACKGROUND: Candidates for commercial spaceflight may be older than the typical astronaut and more likely to have medical problems that place them at risk during flight. Since the effects of microgravity on many medical conditions are unknown, physicians have little guidance when evaluating and certifying commercial spaceflight participants. This dynamic new era in space exploration may provide important data for evaluating medical conditions, creating appropriate medical standards, and optimizing treatment alternatives for long-duration spaceflight. CASE: A 57-yr-old spaceflight participant for an ISS mission presented with medical conditions that included moderately severe bullous emphysema, previous spontaneous pneumothorax with talc pleurodesis, a lung parenchymal mass, and ventricular and atrial ectopy. The medical evaluation required for certification was extensive and included medical studies and monitoring conducted in analogue spaceflight environments including altitude chambers, high altitude mixed-gas simulation, zero-G aircraft, and high-G centrifuge. To prevent recurrence of pneumothorax, we performed video-assisted thoracoscopic pleurodesis, and to assess lung masses, several percutaneous or direct biopsies. The candidate's 10-d mission was without incident. CONCLUSION: Non-career astronauts applying for commercial suborbital and orbital spaceflight will, at least in the near future, challenge aerospace physicians with unknowns regarding safety during training and flight, and highlight important ethical and risk-assessment problems. The information obtained from this new group of space travelers will provide important data for the evaluation and in-flight treatment of medical problems that space programs have not yet addressed systematically, and may improve the medical preparedness of exploration-class missions.

Benefits, unresolved questions, and technical issues of cardiac resynchronization therapy for heart failure.

This review aims to provide a synthesis of the published evidence regarding the rationale and clinical benefits of cardiac resynchronization therapy (CRT) with implantable atrial-synchronized biventricular pacing (BVP) devices in patients with moderate to advanced heart failure and intra- and interventricular conduction delays. In addition, it addresses clinical and technical issues that have yet to be resolved, such as the selection of the most suitable candidates for CRT; the usefulness of combining BVP with automatic defibrillation backup; the value of CRT in patients with atrial fibrillation; the importance of alternative sites of pacing, such as the atrial septum and the right ventricular (RV) outflow tract; the harmful effects of the long-standing practice of producing an iatrogenic left bundle branch block by conventional RV pacing in patients receiving standard permanent pacemakers; the question of precisely where on the left ventricle optimal pacing is achieved; and the potential applications of CRT in patients with pediatric or congenital heart disease. Considering how major advances have been achieved since the first clinical application of CRT in 1994, one can be optimistic about the future of the electrotherapeutic management of heart failure.

Reperfusion-related polymorphic ventricular tachycardia as a possible mechanism of sudden death in patients with anomalous coronary arteries.

We describe a patient with anomalous origin of the left coronary artery in whom polymorphic ventricular tachycardia developed immediately after an episode of chest pain with ST segment elevation. This is the first report providing direct evidence that reperfusion arrhythmias may be the cause of sudden death in individuals with anomalous coronary arteries.

Evaluation of the dopamine ß-hydroxylase (DßH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder.

In the present study, we tested the hypothesis that the potent and selective dopamine-ß-hydroxylase (DßH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40mg) in non-treatment seeking participants who metcriteria for cocaine use disorder. Safety analyses revealed that nepicastat was well-tolerated and there were no differences in adverse events observed after nepicastat plus cocaine vs. cocaine alone. In addition, the pharmacokinetic properties of cocaine administration were not altered by nepicastat treatment. Cocaine-induced cardiovascular and subjective effects were evaluated for completers in the cohort randomized to nepicastat (n=13) using a within-subjects statistical analysis strategy. Specifically, the cardiovascular and subjective effects of cocaine were assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main effect of nepicastat to reduce several cocaine-induced positive subjective effects. Taken together, these data indicate that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder.

Pulmonary vein ablation of atrial fibrillation: beyond the traditional.

The present review aims at giving a synthesis on the evolution in the last decade of the catheter-based ablative treatments for atrial fibrillation (AF). We report the rationale of current pulmonary vein (PV) ablation techniques: segmental PV isolation and circumferential PV ablation. The endpoint is the electrical isolation of the PVs from the left atrium, as they house foci triggering AF in 80% to 95% of cases and seem to play a key role in arrhythmia maintenance. Recurrence rates of AF after these PV ablation strategies are very encouraging. Two recent randomized trials, AFFIRM and RACE, showed no significant difference in outcomes between a strategy of pharmacological heart rate control and that of restoration and maintenance of sinus rhythm with antiarrhythmic drugs. However, multicenter randomized trials comparing PV ablation with drug therapy are required. Future refinements in catheter technology and navigation systems should provide simpler and faster procedures and render PV ablation more widespread and accepted from the scientific and medical communities.

Syncope in adults: systematic review and proposal of a diagnostic and therapeutic algorithm.

This review aims to provide a practical and up-to-date description on the relevance and classification of syncope in adults as well as a guidance on the optimal evaluation, management and treatment of this very common clinical and socioeconomic medical problem. We have summarized recent active research and emphasized the value for physicians to adhere current guidelines. A modern management of syncope should take into account 1) use of risk stratification algorithms and implementation of syncope management units to increase the diagnostic yield and reduce costs; 2) early implantable loop recorders rather than late in the evaluation of unexplained syncope; and 3) isometric physical counter-pressure maneuvers as first-line treatment for patients with neurally-mediated reflex syncope and prodromal symptoms.

Dobutamine stress echocardiography in a patient with Wolff-Parkinson-White syndrome.

We describe the case of a patient with ventricular pre-excitation who underwent dobutamine stress echocardiography to evaluate atypical chest pain. The patient safely underwent the procedure with interesting electrocardiographic findings during pharmacological stress. The risks of dobutamine stress testing, along with possible explanations of this observed event, are discussed. In conclusion, the safety of dobutamine stress testing in patients with ventricular pre-excitation has not been established; further prospective studies are needed to decide whether dobutamine stress testing is safe in certain subsets of this population.

Reducing ischaemia/reperfusion injury through delta-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling.

AIMS: The purpose of this study was to determine whether intrinsic cardiac adrenergic (ICA) cells release calcitonin gene-related peptide (CGRP), exerting synergistic adrenopeptidergic cardioprotection. METHODS AND RESULTS: In situ hybridization coupled with immunostaining demonstrated that ICA cells exclusively expressed CGRP mRNA and co-expressed CGRP and delta-opioid receptor in human and rat left ventricular (LV) myocardium. Radioimmunoassay detected constitutive CGRP release from ICA cells in human and rat hearts. The delta-opioid agonist [D-Pen(25)]-enkephalin (DPDPE) increased CGRP release from ICA cells in denervated rat heart. In an ischaemia/reperfusion rat model, pre-ischaemic treatment with DPDPE reduced infarct size (IS) by 51 +/- 16% (P < 0.01). Co-infusion of beta(2)-adrenergic receptor (beta(2)-AR) and CGRP receptor (CGRP-R) antagonists increased IS by 62 +/- 23% (P < 0.01) compared with saline and abolished DPDPE-initiated IS reduction. Pre-treatment of ICA cell-myocyte co-culture with the beta(2)-AR/CGRP-R antagonists increased myocyte death rate by 24 +/- 4% (P < 0.01) and abolished DPDPE-initiated myocyte protection against hypoxia/reoxygenation (re-O(2)). In the ICA cell-depleted myocyte culture, DPDPE did not confer myocyte protection. Supplementing ICA cell-depleted myocyte culture with beta(2)-AR/CGRP-R agonists reduced hypoxia/re-O(2)-induced myocyte death by 24 +/- 5% (P < 0.01), simulating endogenous neurohormonal effects of ICA cells. Western blot analysis showed that DPDPE markedly increased phosphorylated myocardial Akt levels. This effect was abolished in the presence of beta(2)-AR/CGRP-R blockade. Terminal dUTP nick-end labelling staining analysis of the LV infarct zone demonstrated that DPDPE reduced myocyte apoptosis by 58 +/- 19% (P < 0.05), an effect that was eliminated in the presence of beta(2)-AR/CGRP-R blockade. Finally, echocardiography showed that DPDPE increased LV contractility in a manner dependent on beta-AR/CGRP-R stimulation. CONCLUSION: ICA cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion.

Sudden death prophylaxis in heart failure.

Sudden cardiac death (SCD) is the leading cause of mortality in heart failure (HF). Today the implantable cardioverter-defibrillator (ICD) has become a commonplace therapy around the world for patients with both ischemic and non-ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF alone does not discriminate between the modes of death from HF (sudden arrhythmic death vs. non-sudden death). Other risk statifiers, such as electrophysiologic study and microvolt T-wave alternans testing, should therefore be used in the appropriate settings to minimize the number of unnecessary device implants. In addition, left ventricular mechanical dyssynchrony has now become recognized as an additional major marker of cardiac mortality. Its assessment should entail echocardiography rather than measurement of the QRS duration. This will allow us to better integrate the ability of cardiac resynchronization therapy (CRT) in enhancing cardiac function with the ability of an ICD in preventing SCD. This review aims to: 1) give a synthesis of the published evidence regarding the value of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss controversial clinical issues in this area; and 3) recommend practical device-based management strategies.

A human cardiopulmonary model: extension to LV dysfunction.

We update a cardiopulmonary (CP) model previously developed by our group, more convincingly validate the model with additional hemodynamic and echocardiographic data, and demonstrate the utility of the model by extending it to the simulation of left ventricular diastolic dysfunction (LVDD) via a simple parameter change. The model has considerable potential for the characterization of complex cardiopulmonary diseases such as right or left ventricular failure, valve dysfunction, primary pulmonary hypertension, and acute respiratory distress syndrome (ARDS).

Role of transesophageal echocardiography guided cardioversion in patients with atrial fibrillation, previous left atrial thrombus and effective anticoagulation.

AIMS: The value of transesophageal echocardiography (TEE) to prevent cardioversion-related thromboembolic events in patients with atrial fibrillation (AF) and left atrial (LA) thrombus is unclear. We compared the embolic risk associated with a strategy of follow-up TEE-guided direct-current cardioversion (DCCV) with that of blind DCCV in patients with AF, pre-existing LA thrombus and effective anticoagulation. METHODS AND RESULTS: We identified 67 subjects with TEE-documented LA appendage thrombi from a total of 520 consecutive patients with symptomatic non-rheumatic AF who were referred to us for elective DCCV. All patients received at least 4 weeks of effective warfarin therapy (target international normalized ratio, 2 to 3) before and after DCCV. At time of DCCV, 20 patients had TEE and 47 did not. There were no clinical and echocardiographic differences between the two groups. Thrombus resolution was documented in 18 (90%) patients. After a median follow-up of 4 weeks, two transient ischemic attacks were observed in patients who were blindly cardioverted and one in patients belonging to the TEE group. Sinus rhythm was documented at the time of each thromboembolic event. By multiple logistic regression analysis the TEE strategy was not associated with lower risk of thromboembolism as compared to blind DCCV (odds ratio 1.37; 95% confidence interval, 0.16% to 15.86%; p=0.20). CONCLUSION: In patients with AF, LA thrombus and effective anticoagulation, there is no difference in the risk of clinical thromboembolism between DCCV with or without follow-up TEE. Benefits of warfarin are related to thrombus resolution and prevention of new thrombus formation.

Electrocardiogram of acute ST-elevation myocardial infarction: the significance of the various "scores".

The Electrocardiogram has extensively been used for evaluation and triage of patients with acute chest pain. The clinician admitting a patient with ST elevation acute myocardial infarction should be able to estimate the size and location of the ischemic area at risk, how much of the ischemic myocardium has already undergone irreversible necrosis by the time of presentation, and the "severity of ischemia" (or what is the rate of progression of necrosis as long as ischemia continues). The electrocardiographic variables that are used to make these estimates are the initial portion of the QRS (Q and R waves), the terminal portion of the QRS (the S waves and the J-point), the ST segment, and the configuration of the T waves. This editorial discuss the ability to predict each of the "physiological" parameters using the above mentioned electrocardiographic variables.

An unusual electrocardiogram artifact: what is its source?

A diabetic female presented with nausea and vomiting. Her electrocardiogram showed sinus rhythm with two artifactual spikes, not synchronized with the cardiac rhythm. The patient had an implanted gastric electrical stimulation system for treating her diabetic gastroparesis. Recent DC shock for ventricular fibrillation during coronary angiography caused malfunction of the gastric pacemaker.

Cardiac arrhythmias in cardiothoracic surgery.

Most patients with cardiopulmonary disease are predisposed to develop perioperative arrhythmias with the individual patient risk depending upon the type of operative procedure performed, the risk profile of the patient, and the complexity of the post-operative course. There are several management options that may tend to prevent perioperative arrhythmias that should be considered in certain patient subsets. Most important of these is the use of beta-blocker therapy before and after operation in patients with coronary risks factors undergoing non-cardiac thoracic procedures and in patients having coronary artery bypass grafting. The common supraventricular arrhythmias including atrial fibrillation and flutter, multifocal atrial tachycardia, and paroxysmal supraventricular tachycardia must be properly diagnosed and treated appropriately. Placement of atrial pacing wires for use after open cardiac surgery is of great value both for diagnosis, and in some cases, for treatment of arrhythmias. Fortunately, serious life threatening ventricular arrhythmias occurs less commonly but the clinician must recognize and correct important predisposing factors and know how to treat these when they occur. A specific protocol for arrhythmia management that sets guidelines for drug choice and therapies for each of the common arrhythmias is useful for clinicians and adds predictability to patient care.

Unusual evolution of ST elevation acute myocardial infarction.

We report a case of acute ST-segment elevation myocardial infarction with an unusual evolution of ST-segment elevation. Several possible explanations of this progression are discussed with supportive evidence for each explaination. The clinical, electrocardiographic, and angiographic features of this case are also illustrated.