David L. Ware

Monomorphic ventricular tachycardia: a late complication of percutaneous alcohol septal ablation for hypertrophic cardiomyopathy.

Percutaneous alcohol septal ablation has emerged as a promising treatment option for patients with symptomatic hypertrophic obstructive cardiomyopathy. Although the procedure involves an alcohol-induced myocardial infarction and results in a substrate potentially conducive to re-entrant tachyarrhythmias, late-occurring ventricular arrhythmias have not been described. We report a case of monomorphic ventricular tachycardia occurring several days after alcohol septal ablation. Patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation should be considered for prophylactic placement of implantable cardioverter defibrillator.

Slow Intramural Heating With Diffused Laser Light A Unique Method for Deep Myocardial Coagulation

BACKGROUND Catheter ablation of postinfarction ventricular tachycardia (VT) may be limited by insufficient myocardial coagulation or excessive endocardial or epicardial damage. We propose that volumetric heating restricted to intramural sites may improve the outcome and safety of this procedure, especially if delivered at rates that enhance heat conduction and forestall adverse tissue changes. METHODS AND RESULTS A novel optical fiber with a diffusing tip for direct intramural, volumetric laser heating was tested via thoracotomy and percutaneously in normal dogs. Low-power (2.0- to 4.5-W) diode laser light (805 nm) diffused within tissue induced large lesions but no visible surface damage, mural thrombi, or transmural perforation. Mean lesion depth approximated tip length (10 mm). Mean lesion widths in the thoracotomy and percutaneous groups were 5.8+/-0.5 to 9.1+/-0.84 mm and 5.2+/-0.85 to 7.9+/-1.1 mm, respectively, depending on the light dose. Mean volumes in the percutaneous group were 1006+/-245 to 2471+/-934 mm. ST-segment depression, appearing in unfiltered bipolar electrograms recorded from the guiding catheter, was specific for lesion induction. All dogs survived the protocol, which included a 1-hour observation period. In cross section, lesions were elliptical to spherical and characterized by extensive contraction-band necrosis abruptly bordering viable tissue. No platelets or fibrin adhered to the endocardium. CONCLUSIONS Slow, volumetric, and direct intramyocardial heating induces large, deep lesions without hazardous tissue damage. Such heating might cure postinfarction VT more successfully and safely than present techniques. Further testing and development of this method seem warranted.

Reducing ischaemia/reperfusion injury through δ-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.

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.

Ventricular Defibrillation in Canines with Chronic Infarction, and Effects of Lidocaine and Procainamide

Prior studies in dogs with normal hearts have demonstrated that lidocaine increases but procainamide does not change the energy required for successful defibrillation. Because many postinfarct patients receiving implantable cardioverter defibrillator devices require adjunctive antiarrhythmic therapy, we have studied the effects of lidocaine and procainamide on the relationship between delivered voltage and defibrillation success in mongrel dogs 21 ± 3 days following ligation of the left anterior descending and first diagonal coronary arteries. Internal defibrillation testing using a patch‐patch electrode configuration was performed before and during the administration of saline controls (n = 10), lidocaine (n = 10) and procainamide (n = 10). The mean infarct size as determined by staining with tetrazolium was 13.4%± 8.3% of right and left ventricles, and did not differ significantly between groups. The 50% effective defibrillation (ED50) voltage increased with infusions of saline (16%± 15%), lidocaine (40%± 22%), and procainamide (13%± 15%) and the ED50 energy increased 41%± 44%, 104%± 62%, ond 35%± 36%, respectively. However, the increase in ED50 voltages and energies were significantly greater in animals receiving lidocaine compared to those receiving either saline control or procainamide (P < 0.01). There were trends toward change of hemodynamic parameters in all animals following baseline defibrllation testing, stroke volume declined 21%± 16%, and mean pulmonary artery and aortic pressure increased by 22%± 25% and 11%± 15%, respectively. In conclusion, unlike our previous studies in dogs with normal hearts, in this model hemodynamic deterioration occurred with repeated fibrillation and defibrillation, and defibrillotion voltage requirements increased in the control series. Taking into consideration the increase in defibrillation voltage requirements over the duration of the experiments, lidocaine increases and procainamide does not change ED50; thus, their effects are similar in normal and infarcted canine hearts.

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.

Modeling left ventricular diastolic dysfunction: classification and key indicators

BackgroundMathematical 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.MethodsWe 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.ResultsIR-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.ConclusionThe 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.

A Mechanical Model of the Human Heart Relating Septal Function to Myocardial Work and Energy

A thorough understanding of ventricular interaction and the effects of septal function on right and left ventricular performance in the human heart requires measurement of interventricular pressure gradients using high fidelity pressure transducers. The advent of newer echocardiographic techniques provides an opportunity to combine high resolution images with bi-ventricular catheterization data in the cardiac catheterization laboratory, and obtain the detailed hemodynamic and echocardiographic information necessary to more fully understand the clinical manifestations of normal and abnormal septal and free wall mechanical function. We have anticipated these developments and modified the description of heart mechanics in our integrated multi-scale model of the human cardio-respiratory system (H-CRS) to closely analyze how the mechanical properties of the inter-ventricular septum affect the work, energy utilization, and oxygen consumption of the atria, ventricles, septum, and each ventricular free wall. Combined with the H-CRS model, these modifications allow one to observe how tissue properties of the septum affect the entire heart and circulation. For example, the normal septum transfers energy from the left to the right ventricle, and assists the pre-load of both, acting as a third pump. Diseases that increase septal elastance cause abnormalities resembling left ventricular diastolic dysfunction (LVDD), including a decrease in cardiac output and an increase in pulmonary pressures despite a normal left ventricular ejection fraction. Similar applications of the H-CRS model to other regional disorders such as hypertrophic obstructive cardiomyopathy and myocardial infarction might likewise allow one to study their clinical implications in greater detail.

Cerebral autoregulation and gas exchange studied using a human cardiopulmonary model

We have previously developed a model of human cardiopulmonary (CP) system, which included the whole body circulatory system, gas exchange at both lungs and peripheral tissue, and central nervous control of arterial pressure and ventilation. We now add a more detailed description of cerebral circulation, cerebrospinal fluid (CSF) dynamics and brain gas exchange. Two cerebral blood flow (CBF) regulatory mechanisms are included: autoregulation and CO/sub 2/ reactivity. The cerebral model is first validated in an open-loop configuration using input data generated by the cardiopulmonary model as inputs, then is integrated into the CP model to form an integrated CP model. It is this integrated model that we used to study the response to thigh cuff experiment. Our model demonstrated the ability to closely mimic the experimental findings and to provide predictions regarding the state of cerebral autoregulation and brain tissue gas-exchange. With further refinement, it may serve as a useful tool in clinical evaluation of the cerebral autoregulation and brain oxygenation.

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.