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Chronic therapy with non-excitatory cardiac contractility modulation electric signals improves left ventricular function, reduces myocardial oxygen consumption and increases myocardial mechanical efficiency
S44 present. The Randles’ plot (|Z| vs. 1/√) differential coefficient was 15614 ⍀.s1/2 in a single superior experiment where this was able to be determined. The underlying equivalent circuit is a bulk resistance in series with a YARC-class diffusional element. Conclusion Human fetal skin is a well-behaved circuit element with a predictable equivalent circuit and aggregate resistance for pacing. This supports the practicability of the monolithic fetal pacemaker. Support: National Institute of Health NIH HHS 1R43 HL 67520-01.
AB22-5 CHRONIC THERAPY WITH NON-EXCITATORY CARDIAC CONTRACTILITY MODULATION ELECTRIC SIGNALS IMPROVES LEFT VENTRICULAR FUNCTION, REDUCES MYOCARDIAL OXYGEN CONSUMPTION AND INCREASES MYOCARDIAL MECHANICAL EFFICIENCY *Hani N. Sabbah, PhD, Makoto Imai, MD, Sharad Rastogi, MD, Naveen Sharma, PhD, Margaret P. Chandler, PhD, *Walid Haddad, PhD, *Yuval Mika, PhD and *William C. Stanley, PhD. Henry Ford Health System, Detroit, MI, Case Western Reserve University, Cleveland, OH and Impulse Dynamics, Mount Laurel, NJ. Background: In dogs with heart failure (HF), left ventricular (LV) ejection fraction (EF) increases during acute (2-4 hours) therapy with non-excitatory cardiac contractility modulation (CCM) electric signals delivered to the cardiac muscle during the absolute refractory period. The chronic effects of CCM therapy, however, are not known and were examined in this study. Methods: Studies were performed in 14 dogs with multiple sequential intracoronary microembolization-induced HF. All dogs were implanted with CCM leads and generators (OPTIMIZERTM-II, Impulse Dynamics USA). CCM leads, one each, were fixed to the right ventricular anterior and posterior mid-septal grooves. A third sensing lead was positioned in the right atrium. Dogs were randomized to 3 months of no therapy (ShamControls, n⫽7) or to 3 months of CCM monotherapy (CCM-Treated, n⫽7). The CCM therapy regimen was 5 hours/day based on a duty cycle of one hour ON (CCM signal ⫾ 7.73 volts) and 3 hours and 48 minutes OFF. LV EF, end-systolic (ESV) and end-diastolic (EDV) volumes, myocardial oxygen consumption (MVO2), and myocardial mechanical efficiency (EFF) were measured before (PRE) and 3 months after initiating therapy (POST). Results: The results are shown in the table. In Sham-Controls, LV EF and EFF decreased while EDV, ESV, and MVO2 increased. In contrast, CCM therapy increased LV EF and EFF and reduced EDV, ESV, and MVO2. Conclusion: In dogs with HF, chronic CCM therapy leads to marked improvement in LV function that is associated with reduced MVO2 and increased myocardial EFF all of which are desirable features of therapies targeted to the treatment of HF.
Heart Rhythm, Vol 2, No 5, May Supplement 2005 AB22-6 LONG-TERM MONITORING OF SLEEP APNEA USING AN IMPLANTED DEVICE *Christoph Scharf, MD, *Sameh Sowelam, PhD, *Yong K. Cho, PhD, *Ulla Strobel, *Mark Erickson, BS, *Toby Markowitz, BS and *Konrad Bloch, MD. University Hospital of Zurich, Zurich, Switzerland and Medtronic, Inc., Minneapolis, MN. Background: Patients with cardiovascular disease are at high-risk for sleep related respiratory disorders. Untreated sleep apnea in the pacemaker (PM) population has recently gained attention of researchers. We investigated a PM-based algorithm to detect sleep apnea syndrome based on sensing minute ventilation (MV). Also, nightly variability of sleep apnea status was assessed through ambulatory monitoring during 12 consecutive nights. Methods: 9 Patients (70 ⫾ 7y, 6 m) with a Medtronic Kappa 400 PM underwent an overnight sleep study via polysomnography (PSG). Simultaneously, the PM automatically measured sleep-disordered breathing (PMSDB) in real-time using MV. Data were stored in PM memory. A sleep physician, blinded to the PM memory, analyzed the PSG according to standard criteria and reported apnea-hypopnea index (AHI). PMSDB performance was compared to AHI. PMSDB was monitored and stored for 11 subsequent nights while ambulatory. Results: PMSDB and AHI for the first night correlated significantly (r ⫽ 0.9, p ⬍ 0.001, AHI ⫽ 0.23 * PMSDB). AHI of 15 is an often-used clinical threshold for initiation of sleep apnea therapy. 0.23 * PMSDB correctly predicted AHI to be above or below 15 in all but one patient. PMSDB did not significantly differ night to night (repeated measures ANOVA, p ⫽ 0.97) and did not affect prediction of AHI above or below 15. Conclusion: PM-based sleep apnea screening is feasible and may be useful in monitoring of night-to-night variability.
ABSTRACT SESSION 23: PEDIATRIC/ADULT CONGENITAL HEART DISEASE I: Pediatric Electrophysiology Thursday, May 5, 2005 4:30 p.m.– 6:00 p.m. AB23-1 PHENOTYPIC CHARACTERIZATION OF TIMOTHY SYNDROME A COMPLEX CARDIAC AND MULTISYSTEM DISORDER Raffaella Bloise, MD, Katherine W. Timothy, BS, Carlo Napolitano, MD, PhD, Igor Splawski, BS, Peter J. Schwartz, MD, Mark T. Keating, MD and Silvia G. Priori, MD, PhD. IRCCS, Fondazione Salvatore Maugeri, Pavia, Italy, University of Utah, Salt Lake City, UT, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy, Children’s Hospital, Harvard Medical School, Boston, MA, University of Pavia, Pavia, Italy and IRCCS Fondazione Salvatore Maugeri University of Pavia, Pavia, Italy. Timothy syndrome (TS) is a rare variant of Long QT Syndrome (LQT8). We have recently reported a mutation in the cardiac voltage-gated calcium channel (Cav1.2) in several TS patients (pts). However, the clinical features and genotype-phenotype correlation of TS remain poorly investigated. Here, we report the phenotypic characterization of the largest series of TS patients studied so far. Twenty children with TS have been thor-
AB22-5 CHRONIC THERAPY WITH NON-EXCITATORY CARDIAC CONTRACTILITY MODULATION ELECTRIC SIGNALS IMPROVES LEFT VENTRICULAR FUNCTION, REDUCES MYOCARDIAL OXYGEN CONSUMPTION AND INCREASES MYOCARDIAL MECHANICAL EFFICIENCY *Hani N. Sabbah, PhD, Makoto Imai, MD, Sharad Rastogi, MD, Naveen Sharma, PhD, Margaret P. Chandler, PhD, *Walid Haddad, PhD, *Yuval Mika, PhD and *William C. Stanley, PhD. Henry Ford Health System, Detroit, MI, Case Western Reserve University, Cleveland, OH and Impulse Dynamics, Mount Laurel, NJ. Background: In dogs with heart failure (HF), left ventricular (LV) ejection fraction (EF) increases during acute (2-4 hours) therapy with non-excitatory cardiac contractility modulation (CCM) electric signals delivered to the cardiac muscle during the absolute refractory period. The chronic effects of CCM therapy, however, are not known and were examined in this study. Methods: Studies were performed in 14 dogs with multiple sequential intracoronary microembolization-induced HF. All dogs were implanted with CCM leads and generators (OPTIMIZERTM-II, Impulse Dynamics USA). CCM leads, one each, were fixed to the right ventricular anterior and posterior mid-septal grooves. A third sensing lead was positioned in the right atrium. Dogs were randomized to 3 months of no therapy (ShamControls, n⫽7) or to 3 months of CCM monotherapy (CCM-Treated, n⫽7). The CCM therapy regimen was 5 hours/day based on a duty cycle of one hour ON (CCM signal ⫾ 7.73 volts) and 3 hours and 48 minutes OFF. LV EF, end-systolic (ESV) and end-diastolic (EDV) volumes, myocardial oxygen consumption (MVO2), and myocardial mechanical efficiency (EFF) were measured before (PRE) and 3 months after initiating therapy (POST). Results: The results are shown in the table. In Sham-Controls, LV EF and EFF decreased while EDV, ESV, and MVO2 increased. In contrast, CCM therapy increased LV EF and EFF and reduced EDV, ESV, and MVO2. Conclusion: In dogs with HF, chronic CCM therapy leads to marked improvement in LV function that is associated with reduced MVO2 and increased myocardial EFF all of which are desirable features of therapies targeted to the treatment of HF.
Heart Rhythm, Vol 2, No 5, May Supplement 2005 AB22-6 LONG-TERM MONITORING OF SLEEP APNEA USING AN IMPLANTED DEVICE *Christoph Scharf, MD, *Sameh Sowelam, PhD, *Yong K. Cho, PhD, *Ulla Strobel, *Mark Erickson, BS, *Toby Markowitz, BS and *Konrad Bloch, MD. University Hospital of Zurich, Zurich, Switzerland and Medtronic, Inc., Minneapolis, MN. Background: Patients with cardiovascular disease are at high-risk for sleep related respiratory disorders. Untreated sleep apnea in the pacemaker (PM) population has recently gained attention of researchers. We investigated a PM-based algorithm to detect sleep apnea syndrome based on sensing minute ventilation (MV). Also, nightly variability of sleep apnea status was assessed through ambulatory monitoring during 12 consecutive nights. Methods: 9 Patients (70 ⫾ 7y, 6 m) with a Medtronic Kappa 400 PM underwent an overnight sleep study via polysomnography (PSG). Simultaneously, the PM automatically measured sleep-disordered breathing (PMSDB) in real-time using MV. Data were stored in PM memory. A sleep physician, blinded to the PM memory, analyzed the PSG according to standard criteria and reported apnea-hypopnea index (AHI). PMSDB performance was compared to AHI. PMSDB was monitored and stored for 11 subsequent nights while ambulatory. Results: PMSDB and AHI for the first night correlated significantly (r ⫽ 0.9, p ⬍ 0.001, AHI ⫽ 0.23 * PMSDB). AHI of 15 is an often-used clinical threshold for initiation of sleep apnea therapy. 0.23 * PMSDB correctly predicted AHI to be above or below 15 in all but one patient. PMSDB did not significantly differ night to night (repeated measures ANOVA, p ⫽ 0.97) and did not affect prediction of AHI above or below 15. Conclusion: PM-based sleep apnea screening is feasible and may be useful in monitoring of night-to-night variability.
ABSTRACT SESSION 23: PEDIATRIC/ADULT CONGENITAL HEART DISEASE I: Pediatric Electrophysiology Thursday, May 5, 2005 4:30 p.m.– 6:00 p.m. AB23-1 PHENOTYPIC CHARACTERIZATION OF TIMOTHY SYNDROME A COMPLEX CARDIAC AND MULTISYSTEM DISORDER Raffaella Bloise, MD, Katherine W. Timothy, BS, Carlo Napolitano, MD, PhD, Igor Splawski, BS, Peter J. Schwartz, MD, Mark T. Keating, MD and Silvia G. Priori, MD, PhD. IRCCS, Fondazione Salvatore Maugeri, Pavia, Italy, University of Utah, Salt Lake City, UT, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy, Children’s Hospital, Harvard Medical School, Boston, MA, University of Pavia, Pavia, Italy and IRCCS Fondazione Salvatore Maugeri University of Pavia, Pavia, Italy. Timothy syndrome (TS) is a rare variant of Long QT Syndrome (LQT8). We have recently reported a mutation in the cardiac voltage-gated calcium channel (Cav1.2) in several TS patients (pts). However, the clinical features and genotype-phenotype correlation of TS remain poorly investigated. Here, we report the phenotypic characterization of the largest series of TS patients studied so far. Twenty children with TS have been thor-