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Biomedical subjects

P A Friedman

Publications and source records attributed to P A Friedman.

At least 19 recordsLinked to original sources
PubMed2002

Intracardiac echocardiography.

This article describes currently available intracardiac ultrasound (ICE) technology contrasting it with intravascular ultrasound (IVUS) highlighting their differences. Clinical applications in the electrophysiologic and cardiac catheterization laboratory are discussed and current limitations addressed. Intracardiac echocardiography (ICE) is possible because lower frequency transducers (in contrast to higher frequency IVUS devices) have been miniaturized and mounted onto catheters capable of percutaneous insertion into the heart. These lower frequency transducers are capable of enhanced tissue penetration, permitting high-resolution 2D "whole heart" imaging. Also, with the introduction of the newest phased array transducer, Doppler hemodynamic data in addition to high resolution imaging can also be obtained. ICE facilitates electrophysiologic procedures by guiding transseptal catheterization, enabling endocardial anatomy visualization and targeting of arrhythmogenic substrate, ensuring optimal ablation electrode/tissue contact and promptly diagnosing procedural complications. Promising non-electrophysiologic applications include guidance of percutaneous closure of septal defects, percutaneous mitral balloon valvuloplasty and complex cardiac biopsy. Current limitations include monoplanar imaging, narrow field of view, and relatively large size of the catheter. Intra-cardiac imaging is now a clinical tool and has the potential to play an important role in diagnostic and therapeutic interventional procedures. Further refinement and miniaturization of these transducers, through continued technological progress, will make way for primary operator controlled, integrated ultrasound-guided interventional devices.

Angioplasty, Balloon↗
PubMed2001

Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.

BACKGROUND: Approximately 25% of patients who receive an implantable cardioverter-defibrillator (ICD) to treat ventricular tachyarrhythmias have documented atrial tachyarrhythmias before implantation. This study assessed the ability of device-based prevention and termination therapies to reduce the burden of spontaneous atrial tachyarrhythmias. METHODS AND RESULTS: Patients with a standard indication for the implantation of an ICD and 2 episodes of atrial tachyarrhythmias in the preceding year received a dual-chamber ICD (Medtronic 7250 Jewel AF) that uses pacing and shock therapies for prevention and/or termination of atrial tachyarrhythmias. In a multicenter trial, patients were randomized to 3-month periods with atrial therapies "on" or "off" and subsequently crossed over. Analysis was performed on the 52 of 269 patients who had episodes of atrial tachyarrhythmia and had >/=30 days of follow-up with atrial therapies on and off. The atrial therapies resulted in a reduction of atrial tachyarrhythmia burden from a mean of 58.5 to 7.8 h/mo. A paired analysis (Wilcoxon signed-rank test) showed that the median difference in burden (1.1 h/mo) was highly significant (P=0.007). When the subgroup of 41 patients treated only with atrial pacing therapies was analyzed, the reduction in burden persisted (P=0.01). CONCLUSIONS: In this study, patients with a standard ICD indication and atrial tachyarrhythmias had a significant reduction in atrial tachyarrhythmia burden with use of atrial pacing and shock therapies.

Aged↗
PubMed2001

The implantable cardioverter defibrillator.

Implantable cardioverter defibrillators (ICDs) have evolved from the treatment of last resort to the gold standard therapy for patients at high risk for ventricular tachyarrhythmias. High-risk patients include those who have survived life-threatening arrhythmias, and individuals with cardiac diseases who are at risk for such arrhythmias, but are symptomless. Use of an ICD will affect the patient's quality of life. Some drugs can substantially affect defibrillator function and efficacy, and possible drug-device interactions should be considered. Patients with ICDs may encounter cell phones, antitheft detectors, and many other sources of potential electromagnetic Interference. In addition to treating ventricular tachyarrhythmias, new defibrillators provide full featured dual chamber pacing, and could treat atrial arrhythmias, and congestive heart failure by means of biventricular pacing.

Arrhythmias, Cardiac↗
PubMed2001

Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation that is refractory to drug therapy, radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemaker are an alternative therapeutic approach. The effect of this procedure on long-term survival is unknown. METHOD: We studied all patients who underwent ablation of the atrioventricular node and implantation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival was compared with the survival rates in two control populations: age- and sex-matched members of the Minnesota population between 1970 and 1990 and consecutive patients with atrial fibrillation who received drug therapy in 1993. RESULTS: A total of 350 patients (mean [+/-SD] age, 68+/-11 years) were studied. During a mean of 36+/-26 months of follow-up, 78 patients died. The observed survival rate was significantly lower than the expected survival rate based on the general Minnesota population (P<0.001). Previous myocardial infarction (P<0.001), a history of congestive heart failure (P=0.02), and treatment with cardiac drugs after ablation (P=0.03) were independent predictors of death. Observed survival among patients without these three risk factors was similar to expected survival (P=0.43). None of the 26 patients with lone atrial fibrillation died during follow-up (37+/-27 months). The observed survival rate among patients who underwent ablation was similar to that among 229 controls with atrial fibrillation (mean age, 67+/-12 years) who received drug therapy (P=0.44). CONCLUSIONS: In the absence of underlying heart disease, survival among patients with atrial fibrillation after ablation of the atrioventricular node is similar to expected survival in the general population. Long-term survival is similar for patients with atrial fibrillation, whether they receive ablation or drug therapy. Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adversely affect long-term survival.

Adult↗
PubMed2001

Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets.

The cloning of the so-called 'parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases.

Animals↗
PubMed2001

Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?

Inappropriate sinus tachycardia and postural orthostatic tachycardia are ill-defined syndromes with overlapping features. Although sinus node modification has been reported to effectively slow the sinus rate, long-term clinical response has not been adequately assessed. Furthermore, whether patients with postural orthostatic tachycardia would benefit from sinus node modification is unknown. The study prospectively assessed the short- and long-term clinical outcomes of seven consecutive female patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia who were treated with sinus node modification. The study was conducted in a tertiary care center. The electrophysiological and clinical responses were prospectively assessed as defined by autonomic function testing, including Valsalva maneuver, deep breathing, tilt table testing, and quantitative sudomotor axonal reflex testing. Among the study population (mean age was 41+/-6 years), 5 (71%) patients had successful sinus node modification. At baseline, heart rates were 101+/-12 beats/min before modification and 77+/-9 beats/min after modification (P = 0.001). With isoproterenol, heart rates were 136+/-9 and 105+/-12 beats/min (P = 0.002) before and after modification, respectively. The mean heart rate during 24-hour Holter monitoring was also significantly reduced: 96+/-9 and 72+/-6 beats/min (P = 0.005) before and after modification, respectively. Despite the significant reduction in heart rate, autonomic symptom score index (based on ten categories of clinical symptoms) was unchanged before (15.6+/-4.1) and after (14.6+/-3.6) sinus node modification (P = 0.38). Sinus rate can be effectively slowed by sinus node modification. Clinical symptoms are not significantly improved after sinus node modification in patients with inappropriate sinus tachycardia and postural orthostatic tachycardia. A primary subtle autonomic disregulation is frequently present in this population. Sinus node modification is not recommended in this patient population.

Adult↗
PubMed2001

Role of programmed ventricular stimulation and implantable cardioverter defibrillators in patients with idiopathic dilated cardiomyopathy and syncope.

The aim of this study was to evaluate the role of programmed ventricular stimulation and ICDs in patients with idiopathic dilated cardiomyopathy and syncope. Between 1990 and 1998, 54 (mean age 67+/-11 years, 76% men) patients presented with idiopathic dilated cardiomyopathy and syncope. An electrophysiological study was done in 37 of the 54 patients: 10 had inducible sustained monomorphic ventricular tachycardia, 12 had conduction system disease or neurocardiogenic syncope, and 15 had a normal study. Overall, 17 patients received an ICD, 15 patients received a pacemaker, and 22 patients received no device. Nine of the 15 patients with a negative electrophysiological study eventually received an ICD: 3 because they were considered high risk and 6 because of recurrent syncope or presyncope. In the 17 patients who received an ICD, incidence of appropriate shocks at 1 and 3 years was 47% and 74%, respectively, in the inducible sustained monomorphic ventricular tachycardia group, and 40% and 40%, respectively, in the group without inducible sustained monomorphic ventricular tachycardia (P = 0.29, log-rank test). In conclusion, programmed ventricular stimulation is not useful in risk stratification of patients with idiopathic dilated cardiomyopathy and syncope and may delay necessary ICD implantation.

Aged↗
PubMed2001

Intra-atrial conduction block along the mitral valve annulus during accessory pathway ablation: evidence for a left atrial "isthmus".

INTRODUCTION: We observed a change in the atrial activation sequence during radiofrequency (RF) energy application in patients undergoing left accessory pathway (AP) ablation. This occurred without damage to the AP and in the absence of a second AP or alternative arrhythmia mechanism. We hypothesized that block in a left atrial "isthmus" of tissue between the mitral annulus and a left inferior pulmonary vein was responsible for these findings. METHODS AND RESULTS: Electrophysiologic studies of 159 patients who underwent RF ablation of a left free-wall AP from 1995 to 1999 were reviewed. All studies with intra-atrial conduction block resulting from RF energy delivery were identified. Fluoroscopic catheter positions were reviewed. Intra-atrial conduction block was observed following RF delivery in 11 cases (6.9%). This was evidenced by a sudden change in retrograde left atrial activation sequence despite persistent and unaffected pathway conduction. In six patients, reversal of eccentric atrial excitation during orthodromic reciprocating tachycardia falsely suggested the presence of a second (septal) AP. A multipolar coronary sinus catheter in two patients directly demonstrated conduction block along the mitral annulus during tachycardia. CONCLUSION: An isthmus of conductive tissue is present in the low lateral left atrium of some individuals. Awareness of this structure may avoid misinterpretation of the electrogram during left AP ablation and may be useful in future therapies of atypical atrial flutter and fibrillation.

Arrhythmias, Cardiac↗
PubMed2001

Localization of the origin of arrhythmias for ablation: from Electrocardiography to advanced endocardial mapping systems.

Radiofrequency catheter ablation techniques have had a dramatic impact on the treatment of a variety of cardiac arrhythmias. However, catheter ablation of complex arrhythmias, such as intra-atrial reentry, ventricular tachycardias, and atrial fibrillation, continues to pose a major challenge. This stems from limitations of fluoroscopy and conventional catheter-based mapping techniques that limit the accurate anatomic localization of complex arrhythmogenic substrates. In this article, ECG features of complex arrhythmias are reviewed, which may facilitate the planning of an ablation procedure. The physical principles of the newly available catheter-based endocardial mapping techniques and their clinical applicability for treatment of complex arrhythmias are discussed. The role of intracardiac echocardiography to facilitate mapping and ablation is reviewed.

Arrhythmias, Cardiac↗
PubMed2001

Intracardiac echocardiography.

This article describes currently available intracardiac ultrasound (ICE) technology contrasting it with intravascular ultrasound (IVUS), highlighting their differences. General and specific clinical applications, limitations and future developments of ICE are addressed. ICE is possible because lower frequency transducers (in contrast to higher frequency IVUS devices) have been miniaturized and mounted onto catheters capable of percutaneous insertion into the heart. Since the recent availability of a steerable, 5.5--10MHz phased-array catheter with full Doppler capability, these lower frequency transducers are not only capable of enhanced penetration, permitting high-resolution two-dimensional (2D) imaging but can also provide haemodynamic data. ICE facilitates electrophysiologic procedures by guiding trans-septal catheterization, enabling endocardial anatomy visualization, ensuring ablation electrode/tissue contact and promptly diagnosing procedural complications. Promising non-electrophysiologic applications include guidance of percutaneous closure of septal defects, percutaneous mitral balloon valvuloplasty and complex cardiac biopsy. Current limitations include monoplanar imaging and narrow field of view. Expanded diagnostic techniques such as tissue Doppler, multiplane, three dimensional (3D) and multimodality imaging represent future refinements. ICE is now a clinical tool. With the introduction of the newest phased-array transducer, with full Doppler capability, ICE has the potential to play an important role in diagnostic and therapeutic interventional procedures. Further refinement and miniaturization hold the key to primary operator controlled, integrated ultrasound-guided interventional devices.

Arrhythmias, Cardiac↗
PubMed2000

Electrophysiologic characteristics of diverse accessory pathway locations of antidromic reciprocating tachycardia.

This study assessed antidromic reciprocating tachycardia (ART) in patients with paraseptal accessory pathways (APs). Previous clinical experience suggests that paraseptal APs are unable to serve as the anterograde limb during ART. Based on the reentry wavelength concept, we hypothesized that anatomic location of a paraseptal AP may not preclude occurrence of ART. If wavelength criteria were met due to prolonged conduction time retrogradely in the atrioventricular node or anterogradely in the AP, ART may be sustained. All patients who had ART in the electrophysiologic laboratory at our institution (1991 to 1998) were studied. Based on fluoroscopically guided electrophysiologic mapping and radiofrequency ablation, AP location was classified as paraseptal, posterior, or lateral. Conduction time and refractoriness measurements were made for all components of the ART circuit. Of 24 patients with ART, 5 (21%) had ART utilizing a paraseptal AP. Anterograde conduction time through the AP and retrograde atrioventricular nodal conduction time were significantly longer in patients with paraseptal versus lateral pathways. Isoproterenol was required for ART induction in 38% of patients with a posterior AP, 36% with lateral AP location, but not in patients with a paraseptal AP. There were no significant differences in tachycardia cycle length or refractoriness of anterograde and/or retrograde components of the macroreentry circuit between the 3 pathway locations. Thus, ART can occur in patients with a paraseptal AP. Slower anterograde pathway conduction, or retrograde atrioventricular nodal conduction renders the wavelength critical for completion of the antidromic re-entrant circuit.

Adrenergic beta-Agonists↗
PubMed2000

Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin.

The mouse aspartyl beta-hydroxylase gene (Asph, BAH) has been cloned and characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. Monoclonal antibody reagents were generated, epitope-mapped, and used to definitively correlate RNA bands on Northern blots with protein species on Western blots. The gene for mouse junctin, a calsequestrin-binding protein, was cloned and characterized and shown to be encoded from the same locus. When expressed in heart tissue, BAH/humbug preferably use the first exon and often the fourth exon of junctin while preserving the reading frame. Thus, three individual genes share common exons and open reading frames and use separate promoters to achieve differential expression, splicing, and function in a variety of tissues. This unusual form of exon sharing suggests that the functions of junctin, BAH, and humbug may be linked.

Amino Acid Sequence↗
PubMed2000

Global right atrial mapping of human atrial flutter: the presence of posteromedial (sinus venosa region) functional block and double potentials : a study in biplane fluoroscopy and intracardiac echocardiography.

BACKGROUND: Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. METHODS AND RESULTS: Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. CONCLUSIONS: (1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

Adult↗
PubMed2000

Determination of pacing capture in implantable defibrillators: benefit of evoked response detection using RV coil to can vector.

Automatic detection of capture in ICDs would be useful for ensuring normal pacing function and lead integrity and may increase device longevity. Evoked response detection can be difficult due to postpace polarization. Polarization on the RV coil to can vector, however, should be absent when pacing with a true bipolar lead (pace tip to ring). Polarization on the RV coil to can vector should be low in an integrated bipolar lead due to the large surface area of the coil. Ventricular-paced responses were prospectively recorded in 20 patients during ICD implantation or replacement. Capture and loss of capture responses were noted during threshold searches with electrograms recorded between the RV coil and can. A detector was designed to discriminate between capture and noncapture-paced responses using data from the first 11 patients and validated on the remaining 9. The detector had a sensitivity of 99.9% (detected capture on capture beats), and had a specificity of 100% (detected no capture on noncapture beats) for all lead configurations. There was no measurable polarization with true bipolar leads. In integrated bipolar leads, maximum polarization ranged from 0.0 to 16.7 mV. In conclusion, paced evoked responses can be detected in ICDs using the RV coil to can vector using standard pacing waveforms. Special polarization reducing pacing waveforms are not required. These observations could be used to design ICDs with automatic pacing threshold detection.

Adolescent↗
PubMed2000

Wide QRS tachycardia refractory to pharmacologic interventions and cardioversion.

The case of a 43-year-old man with an idiopathic wide QRS tachycardia resistant to adenosine, lidocaine, procainamide, and multiple electric shocks is described. The tachycardia eventually stopped after a pacing wire was introduced in the right ventricle, inducing a run of rapid ventricular tachycardia. The possible causes of resistance to medications and cardioversion, and alternative treatment modalities are reviewed.

Adenosine↗