The surgical treatment of atrial fibrillation: III. Development of a definitive surgical procedure

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

The Clinical Profile and Pathophysiology of Atrial Fibrillation Relationships Among Clinical Features, Epidemiology, and Mechanisms

The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis.

The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation.

We calculated the wavelength of the atrial impulse in chronically instrumented conscious dogs by measuring both conduction velocity and refractory period: wavelength = refractory period X conduction velocity. Implantation of multiple stimulating and recording electrodes allowed wavelength determination at four different areas: the right and left parts of Bachmann's bundle and the free walls of the right and left atria. During programmed electrical stimulation, three types of arrhythmias were observed: rapid repetitive responses, atrial flutter, and atrial fibrillation. During normal rhythm, the wavelength of the atrial impulse varied between 14 and 18 cm. Premature beats had a shorter wavelength, depending on the degree of prematurity. Premature beats that evoked rapid repetitive responses showed a critical shortening of the wavelength below 12.3 cm. Episodes of atrial flutter were induced at a wavelength below 9.7 cm, while fibrillation occurred at wavelengths shorter than 7.8 cm. We correlated the induction of these arrhythmias with the values of refractory period, conduction velocity, and wavelength during control and during administration of several drugs. Intravenous administration of acetylcholine shortened the wavelength by 30-40%, mainly because of refractory period shortening. Both propafenone and lidocaine had strong but opposite effects on refractoriness and conduction and, consequently, little effect on the wavelength. Quinidine markedly prolonged the refractory period, but prolongation of wavelength was less because of a simultaneous decrease in conduction velocity. d-Sotalol also increased refractory period, but because it had no appreciable effect on conduction velocity, this drug was the most effective in prolongation of wavelength. Linear discriminant analysis of the data showed that the refractory period and the conduction velocity each were poor parameters to predict the occurrence of the different arrhythmias (predictive value 48% and 38%, respectively). The combination of both properties, however, as expressed in the wavelength, was a more reliable index that predicted the induction of the different arrhythmias correctly in 75% of the cases. We conclude that the wavelength is a useful parameter for evaluating antiarrhythmic drugs.

Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs.

Natural atrial flutter was discovered In a dog. Two forms of the arrhythmia resembling the human counterparts of typical and atypical atrial flutter were noted. The Observations in this dog led to studies in a series of normal dogs in which the extrastimulus technique was used to evoke runs of repetitive activity simulating but unlike true atrial flutter. Epicardial atrial activation maps were made from 72 to 96 bipolar complexes recorded during the arrhythmias. Multiple effective refractory periods were determined and these values were used to construct maps of the refractory period distribution. Dog 1, with true atrial flutter, demonstrated a complex form of circus motion characterized by unidirectional block and one-way conduction. Abnormal slowing of the unblocked circus wave stabilized and maintained the repetition by permitting more time for recovery of a uniform state of excitability ahead of the wave. The slow conduction in this dog was associated with right atrial hypoplasia and discontinuity in the preferential atrial conduction pathways. The circus activation patterns in the dogs with evoked flutter were similar to those in true flutter; however, the cycle lengths were shorter and the circus wave conducted faster. In evoked flutter the regional differences in refractory period duration determined the one-way block and circus conduction patterns. The circus pattern was caused by a nonuniform bimodal refractory state of the atrium that simultaneously exerted a blocking effect while permitting conduction and complex shaping of the unblocked wave, which was routed back to its site of origin. Thus atrial flutter was the result of three Interacting factors: (1) an atrial premature beat, (2) nonuniform distribution of atrial refractory periods, and (3) slow conduction of the circus wave initiated by factors 1 and 2.

Natural and evoked atrial flutter due to circus movement in dogs

In studies to ascertain the basis of dynamic changes in the P wave, bipolar epicardial potentials were recorded from multiple atrial electrodes in dogs. One hundred to 120 activation times were displayed by a digital computer and used to construct atrial isotemporal activation sequence maps. Changes in heart rate or beat-to-beat cycle length were induced by vagal stimulation or infusion of autonomic mediating drugs. Changes in cycle length were associated with dynamic changes in the atrial activation sequence and surface P-wave. A conspicuous finding was that epicardial atrial depolarization began at three widely separated locations. These three points were consistently present in all animals and were generally located at the 12, 3, and 6 o'clock positions of the superior vena cava-right atrial junction. The dynamic changes in P waves and atrial activation sequence which accompanied the changes in cycle length were due to sudden shifts in the point of earliest activity between the three early sites. Asymmetric atrial depolarization with more rapid conduction along the crista terminalis, superior interatrial band, and pectinate muscles was present in all dogs. Although the anisotropic atrial geometry played an important role in the asymmetric conduction, the widely distributed onset of activity contributed significantly to the uneven spread. The multiple points of origin of the atrial wavefront might be explained by either a trifocal, distributed pacemaker or the epicardial exits of three specialized pathways conducting an impulse emanating from a single focus. These data explain the dynamic variation in P-wave morphology in normal hearts and also imply a relationship between the altered origin of atrial depolarization, atypical P waves, brady- or tachyarrhythmias, and heart rate control.

Multicentric origin of the atrial depolarization wave: The pacemaker complex. Relation to dynamics of atrial conduction, P-wave changes and heart rate control

We present the performance of a CMOS miniaturized (4mm x 3.2mm x 3.3mm) spectrometer for two specific wearable health applications: reflective medically-accurate SpO2 and dermal H2O measurement for preventive health and remote follow-up use cases. The spectrometer has been manufactured using a monolithically integrated filter process, enabling low-cost, low-power, miniature and mass-producible spectral sensors. Accurate biomarker models can be built using continuous on-skin hyperspectral tissue and PPG data. A deoxygenation trial on 17 healthy volunteers was conducted using the wrist-worn spectrometer in the 650-900nm wavelength range. Using partial least squares (PLS) modeling, a model was built to correlate the obtained spectral PPG data to SpO2 data from a reference finger clip (Nonin 8000A). In the tested range between 87% and 100% SpO2, an RMSEP of 1.86%SpO2 has been obtained on a separate test set, well within the 3.5% requirement of the FDA. For dermal skin hydration, a study on 29 volunteers (including 4 patients with congestive heart failure (CHF) and fluid retention in legs) was conducted with the spectrometer in the 750-1050 nm range. A spectroscopic model was compared with a lymph scanner as gold standard measuring localized percentage water content (PWC), yielding a decent prediction accuracy of 3.3% RMSE, while correctly identifying the patients with CHF. We demonstrated the viability of a miniaturized spectrometer for wearable skin biomarker measurements. This solution has the potential to detect other tissue biomarkers such as SpCO or StO2, or to read subdermal markers such as hydrogels for glucose or lactate detection.

Accurate measurement of SpO2 and dermal skin hydration using a wearable miniaturized spectrometer

SUMMARY Instudies toascertain thebasis ofdynamic changes inthePwave,bipolar epicardial potentials wererecorded frommultiple atrial electrodes indogs. Onehundred to120activation times weredisplayed bya digital computer andusedtoconstruct atrial isotemporal activation sequencemaps.Changes inheart rate or beat-to-beat cycle length wereinduced byvagal stimulation orinfusion ofautonomic mediating drugs. Changes incycle length wereassociated withdynamic changes intheatrial activation sequenceandsurface P-wave. A conspicuous finding was thatepicardial atrial depolarization began atthree widely separated locations. These three points wereconsistently present inallanimals andweregenerally located atthe12,3,and6o'clock positions ofthesuperior venacava-right atrial junction. Thedynamic changes inP wavesandatrial activation sequencewhichaccompanied thechanges incycle length wereduetosudden shifts inthepoint ofearliest activity between thethree early sites. Asymmetric atrial depolarization withmore rapid conduction along the crista terminalis, superior interatrial band, andpectinate muscles was present inalldogs. Although the anisotropic atrial geometry played an important roleintheasymmetric conduction, thewidely distributed onsetofactivity contributed significantly totheunevenspread. Themultiple points oforigin oftheatrial wavefront mightbeexplained byeither a trifocal, distributed pacemaker or theepicardial exits ofthree specialized pathways conducting an impulse emanating fromasingle focus. Thesedataexplain thedynamic variation inP-wave morphology innormal hearts andalso imply arelationship between thealtered origin of atrial depolarization, atypical P waves,brady- ortachyarrhythmias, andheart ratecontrol. THISSTUDYWAS DESIGNEDtodetermine the basis forchanges intheconfiguration ofthePwavein thesurface ECG.We wereawareofbeat-to-beat changes inP wavesaccompanying heartrate variations innormal humansubjects. We werealso awareofchanges inwhich transient forms oftheP waveexhibited extreme notching andprolonged duration, resembling left atrial enlargement oratrial conduction delay. Because these patterns wereunstable, changing backtonormal, wesuspected theymight represent dynamic variations intheatrial activation sequence, resulting indelayed left atrial activation. Asaworking hypothesis weconsidered that each different P-wavemorphology reflected a particular atrial activation sequence andthat achange inthePwaveconfiguration wastheresult ofadynamic change

Joseph M. Borremans

Papers

Natural and evoked atrial flutter due to circus movement in dogs

Multicentric origin of the atrial depolarization wave: The pacemaker complex. Relation to dynamics of atrial conduction, P-wave changes and heart rate control

Accurate measurement of SpO2 and dermal skin hydration using a wearable miniaturized spectrometer

Multicentric Origin oftheAtrial Depolarization Wave: ThePacemaker Complex Relation toDynamics ofAtrial Conduction, P-WaveChanges and HeartRateControl