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Symptomatic Heart Failure Is an Uncommon Presentation of Cardiac Sarcoidosis and Is Associated With a Higher Rate of Ventricular Arrhythmias
The 14th Annual Scientific Meeting
193 Do Changes in Repolarization Predict Outcomes in Patients Undergoing Cardiac Resynchronization Therapy? Abhijit Ghatak1, Raja Pullatt1, Vamsi Pavuluri1, Steven Zweibel1, Christopher Clyne1, Jeffrey Kluger1; 1Cardiology, Hartford Hospital, Hartford, CT Introduction: Cardiac resynchronization therapy (CRT) for patients with advanced heart failure improves survival, but 30% of CRT recipients are nonresponders. Cardiac dyssynchrony is known to affect both ventricular depolarization and repolarization. Using ventricular repolarization measures such as QTc dispersion (QTcd) and the T peak to T end interval (Tpe) in addition to established ventricular depolarization parameters (QRS width) may improve predicting the response to CRT. Methods: We retrospectively analyzed data on patients receiving CRT at a single tertiary care hospital. Pre and post CRT implantation surface 12 lead ECGs were measured for QTcd, change in QTcd (D QTcd), Tpe, and change in Tpe (D Tpn). Patients with pre implant pacing and/or atrial fibrillation on ECG were excluded. Definition of nonresponders was death or heart failure related hospital admissions. Results: A total of 158 patients were reviewed with 97 of these meeting inclusion criteria. The mean follow up was 2.1 + /- 0.7 years. A total of 31 patients were nonresponders (6 deaths and 25 hospitalizations). QTcd and D QTcd showed no significant difference in between responders and nonresponders. As shown in the table pre implant Tpe and DTpe differentiated the two groups. Patients with Cardiac Resynchronization Therapy Measures of repolarization (msec) Pre QTcd Post QTcd DQTcd Pre Tpe Post Tpe DTpe
Non responders (Mean)
Responders (Mean)
p value
47.88 50.56 -2.68 98.28 102.41 -4.14
43.97 47.09 -3.11 116.12 111.91 2.50
0.505 0.589 0.958 0.006 0.121 0.056
In a multivariate analysis pre implant Tpe was the only independent predictor of the combined end points of death or heart failure hospitalizations (p 5 0.003). Conclusion: Pre implant Tpe maybe a useful measure of repolarization in predicting patients who may not benefit from cardiac resynchronization therapy.
194 Symptomatic Heart Failure Is an Uncommon Presentation of Cardiac Sarcoidosis and Is Associated With a Higher Rate of Ventricular Arrhythmias Matthew D. Olson1, Matthew M. Zipse1, Joseph L. Schuller1, Diego F. Belardi1, Royce L. Bargas1, Christopher M. Lowery1, Aleong G. Ryan1, Paul D. Varosy2, William H. Sauer1; 1Electrophysiology, University of Colorado, Aurora, CO; 2 Electrophysiology, VA Medical Center, Denver, CO Introduction: Sarcoidosis is a multisystem granulomatous disease affecting multiple organ systems including the heart. Cardiac involvement may be manifested by conduction abnormalities, atrial and ventricular arrhythmias (VT/VF) and heart failure (HF). We sought to characterize the prevalence of HF at the time of diagnosis in our cohort of patients with cardiac sarcoidosis. Methods: Patients with biopsy proven systemic sarcoidosis and symptoms of possible cardiac involvement that initiated referral for evaluation were included in the cohort. We identified 48 patients with cardiac sarcoidosis. New York Heart Association (NYHA) functional class was assessed at the time of confirmation of myocardial involvement. Diagnosis was based upon modified criteria from the Japanese Ministry of Health and Welfare including cardiac MRI. All patients received an implanted cardioverter-defibrillator (ICD) for primary prevention of sudden death. Results: Of the 48 subjects diagnosed with cardiac sarcoidosis, 6 had NYHA functional class II or III symptoms (12.5%). The left ventricular ejection fraction (LVEF) was lower in those with HF symptoms (41.7 + /- 6.7% vs. 58.5 + /- 6.8%; p ! 0.01). A greater prevalence of right ventricular dysfunction was also seen in this group (83.3% vs. 43.2%; p 5 0.09). After a mean follow-up of 31 months the incidence of VT/VF episodes was greater among patients with prevalent HF at the time of diagnosis compared to those without HF (50% vs. 9.5%; p 5 0.03) with a relative risk of 5.25 (95% confidence interval: 1.5, 17.9; p 5 0.02). Conclusions: The prevalence of symptomatic HF is uncommon at the time of diagnosis of cardiac sarcoidosis. Prevalent HF at baseline is associated with left and right ventricular dysfunction and a five-fold greater incidence of VT/VF during follow-up. Further research is required to evaluate methods for screening patients with sarcoidosis to prevent the development of heart failure and subsequent ventricular arrhythmias.
195 Obstructive Sleep Apnea Is Associated with Worsened Oxidative Stress and Treatment Resistance in Atrial Fibrillation R. Valadri, H. Bloom, R. Gadesam, D. Delurgio, D. Jones, S. Bhadriraju; Pulmonology, Emory University, Atlanta, GA Introduction: The epidemiology of obstructive sleep apnea (OSA) in the US is increasing. OSA is a known risk factor for cardiac disease. However, the relationship
HFSA
S61
between OSA and the pathophysiology of atrial fibrillation (AF) is less clear. Recent data has shown that OSA is associated with increased oxidative stress. Previously, we documented the association between oxidative stress and AF. Hypothesis: Patients with OSA and AF will have a worsened oxidative stress profile compared to patients with AF and no OSA. Methods: In a case control study we compared redox potentials of glutathione (EhGSH) and cysteine (EhCyS) among consecutive AF patients with and without OSA who were referred for sleep study. Groups were matched for HTN, CAD, DM and smoking status, known confounders of oxidative stress. OSA in the case group was diagnosed by sleep study and Berlin questionnaire was used in control group to rule out OSA. A single non fasting blood sample was measured for redox potentials at Emory core laboratory. AF history, number and type of interventions were collected retrospectively for 5 years. Exclusion criteria: Severe lung disease requiring home oxygen or oral steroid therapy, MI or CABG within last 6 months, LA diameter more than 5 cm, severe valvular disease, uncontrolled hypertension, CHF and chronic diseases. Results: 10 patients were enrolled in each group. The case group all had a positive sleep study for OSA and all control group patients had a Berlin score of 0. When compared, afib in OSA tend be permanent (mean duration 5 yrs vs. 1 yr; p ! 0.05), resistant to intervention (number of patients with 2 or more interventions; 9 vs. 1; p ! 0.05) and worsened oxidative stress profile. (mean EhGSH -118 6 6mV vs. -139 6 16mV; p 5 0.0038.) Mean values for EhCyS were not different. The number of patients on B blockers, ACE inhibitors and statins (known to alter oxidative stress) were not different. Conclusion: Our data suggest, OSA is associated with worsened oxidative stress and treatment resistance in AF. A significant proportion of elderly population have AF, aggressive evaluation for OSA in new onset afib population is paramount, as it is often under attended by both physicians and patients. Further studies are needed to evaluate the efficacy of treating OSA in afib and the possible role of oxidative stress treatment in this population.
196 Right Phrenic Nerve Stimulation for Apnea in Heart Failure Patients Using a Novel Intravenous Lead Ralph Augostini1, Dariusz Jagielski2, Xilong Zhang3, Shi-Jiang Zhang3, Dariusz Michalkiewicz4, Randy Westlund5; 1The Ohio State University Medical Center, Columbus, OH; 24th Military Hospital, Wroclaw, Poland; 3Jiangsu Province Hospital, Nanjing, China; 4Central Military Hospital, Warsaw, Poland; 5Cardiac Concepts, Minnetonka, MN Introduction: Treatment of sleep disordered breathing (SDB) in heart failure (HF) patients (pts) may improve their HF status. Stimulation of the phrenic nerve (PN) via surgically implanted cuff electrodes has been shown to be effective in modulating respiratory function. Unilateral transvenous stimulation of the PN may allow for treatment of SDB in HF patients. Methods: The right brachiocephalic vein (BCV) was selectively engaged and a venogram performed in pts with HF (mean NYHA Class 2.4) and SDB. Multipolar leads were inserted into the right BCV. Acute stability was assessed using deep breathing and coughing maneuvers under fluoroscopic observation. Stimulation thresholds (ST) were measured in the most stable locations available. Leads remained in situ for a 2-night SDB therapy study. Results: Ten pts. underwent venous access and venography of the right BCV. The lead was deployed into the BCV and electrodes oriented relative the PN in 10-45 minutes. In all pts a position was found that was stable while the patient coughed and performed deep respiration repeatedly. Extra-respiratory sensation (ERS) including shoulder twitch was observed in 1 pt. ERS was successfully mitigated by stimulating from a different electrode pair. No adverse events were observed. Observed Stimulation Thresholds N
Pulse Width (msec)
ST (mA)
Impedance (U)
5 4 1
150 240 300
4.9 6 1.1 4.3 6 0.8 4.0
360 6 71 327 6 71 n/a
Conclusion: Stable acute transvenous stimulation of the phrenic nerve via the right brachiocephalic vein is feasible and well-tolerated. Unilateral right phrenic nerve stimulation is possible without extra-respiratory sensations and may be a basis of treatment for periodic breathing in heart failure patients.
197 Can Disease Etiology Predict Differences in Intra-Ventricular Conduction Delay in CRT patients? Nader Ghaly1, Mary Tiernan1, David Muller2; 1Electrophysiology, AtlatiCare Regional Medical Center, Pomona, NJ; 2CRM, St Jude, Sylmar, CA Introduction: Differences in response to cardiac resynchronization therapy (CRT) can vary depending on disease etiology. It has been suggested that this may be due to alterations in conduction velocities in the ventricle. These changes may be to to the presence or abscence of myocaridal scar formation. Methods: We evaluated retrospective implant data from patients undergoing CRTD implants between 2007 and 2008.(N 5 107) These patients were then divided based on disease etiology into 2 groups, Ischemic (ICM) and Non-Ischemic (NICM) (N 5 86 and 31 respectively)
193 Do Changes in Repolarization Predict Outcomes in Patients Undergoing Cardiac Resynchronization Therapy? Abhijit Ghatak1, Raja Pullatt1, Vamsi Pavuluri1, Steven Zweibel1, Christopher Clyne1, Jeffrey Kluger1; 1Cardiology, Hartford Hospital, Hartford, CT Introduction: Cardiac resynchronization therapy (CRT) for patients with advanced heart failure improves survival, but 30% of CRT recipients are nonresponders. Cardiac dyssynchrony is known to affect both ventricular depolarization and repolarization. Using ventricular repolarization measures such as QTc dispersion (QTcd) and the T peak to T end interval (Tpe) in addition to established ventricular depolarization parameters (QRS width) may improve predicting the response to CRT. Methods: We retrospectively analyzed data on patients receiving CRT at a single tertiary care hospital. Pre and post CRT implantation surface 12 lead ECGs were measured for QTcd, change in QTcd (D QTcd), Tpe, and change in Tpe (D Tpn). Patients with pre implant pacing and/or atrial fibrillation on ECG were excluded. Definition of nonresponders was death or heart failure related hospital admissions. Results: A total of 158 patients were reviewed with 97 of these meeting inclusion criteria. The mean follow up was 2.1 + /- 0.7 years. A total of 31 patients were nonresponders (6 deaths and 25 hospitalizations). QTcd and D QTcd showed no significant difference in between responders and nonresponders. As shown in the table pre implant Tpe and DTpe differentiated the two groups. Patients with Cardiac Resynchronization Therapy Measures of repolarization (msec) Pre QTcd Post QTcd DQTcd Pre Tpe Post Tpe DTpe
Non responders (Mean)
Responders (Mean)
p value
47.88 50.56 -2.68 98.28 102.41 -4.14
43.97 47.09 -3.11 116.12 111.91 2.50
0.505 0.589 0.958 0.006 0.121 0.056
In a multivariate analysis pre implant Tpe was the only independent predictor of the combined end points of death or heart failure hospitalizations (p 5 0.003). Conclusion: Pre implant Tpe maybe a useful measure of repolarization in predicting patients who may not benefit from cardiac resynchronization therapy.
194 Symptomatic Heart Failure Is an Uncommon Presentation of Cardiac Sarcoidosis and Is Associated With a Higher Rate of Ventricular Arrhythmias Matthew D. Olson1, Matthew M. Zipse1, Joseph L. Schuller1, Diego F. Belardi1, Royce L. Bargas1, Christopher M. Lowery1, Aleong G. Ryan1, Paul D. Varosy2, William H. Sauer1; 1Electrophysiology, University of Colorado, Aurora, CO; 2 Electrophysiology, VA Medical Center, Denver, CO Introduction: Sarcoidosis is a multisystem granulomatous disease affecting multiple organ systems including the heart. Cardiac involvement may be manifested by conduction abnormalities, atrial and ventricular arrhythmias (VT/VF) and heart failure (HF). We sought to characterize the prevalence of HF at the time of diagnosis in our cohort of patients with cardiac sarcoidosis. Methods: Patients with biopsy proven systemic sarcoidosis and symptoms of possible cardiac involvement that initiated referral for evaluation were included in the cohort. We identified 48 patients with cardiac sarcoidosis. New York Heart Association (NYHA) functional class was assessed at the time of confirmation of myocardial involvement. Diagnosis was based upon modified criteria from the Japanese Ministry of Health and Welfare including cardiac MRI. All patients received an implanted cardioverter-defibrillator (ICD) for primary prevention of sudden death. Results: Of the 48 subjects diagnosed with cardiac sarcoidosis, 6 had NYHA functional class II or III symptoms (12.5%). The left ventricular ejection fraction (LVEF) was lower in those with HF symptoms (41.7 + /- 6.7% vs. 58.5 + /- 6.8%; p ! 0.01). A greater prevalence of right ventricular dysfunction was also seen in this group (83.3% vs. 43.2%; p 5 0.09). After a mean follow-up of 31 months the incidence of VT/VF episodes was greater among patients with prevalent HF at the time of diagnosis compared to those without HF (50% vs. 9.5%; p 5 0.03) with a relative risk of 5.25 (95% confidence interval: 1.5, 17.9; p 5 0.02). Conclusions: The prevalence of symptomatic HF is uncommon at the time of diagnosis of cardiac sarcoidosis. Prevalent HF at baseline is associated with left and right ventricular dysfunction and a five-fold greater incidence of VT/VF during follow-up. Further research is required to evaluate methods for screening patients with sarcoidosis to prevent the development of heart failure and subsequent ventricular arrhythmias.
195 Obstructive Sleep Apnea Is Associated with Worsened Oxidative Stress and Treatment Resistance in Atrial Fibrillation R. Valadri, H. Bloom, R. Gadesam, D. Delurgio, D. Jones, S. Bhadriraju; Pulmonology, Emory University, Atlanta, GA Introduction: The epidemiology of obstructive sleep apnea (OSA) in the US is increasing. OSA is a known risk factor for cardiac disease. However, the relationship
HFSA
S61
between OSA and the pathophysiology of atrial fibrillation (AF) is less clear. Recent data has shown that OSA is associated with increased oxidative stress. Previously, we documented the association between oxidative stress and AF. Hypothesis: Patients with OSA and AF will have a worsened oxidative stress profile compared to patients with AF and no OSA. Methods: In a case control study we compared redox potentials of glutathione (EhGSH) and cysteine (EhCyS) among consecutive AF patients with and without OSA who were referred for sleep study. Groups were matched for HTN, CAD, DM and smoking status, known confounders of oxidative stress. OSA in the case group was diagnosed by sleep study and Berlin questionnaire was used in control group to rule out OSA. A single non fasting blood sample was measured for redox potentials at Emory core laboratory. AF history, number and type of interventions were collected retrospectively for 5 years. Exclusion criteria: Severe lung disease requiring home oxygen or oral steroid therapy, MI or CABG within last 6 months, LA diameter more than 5 cm, severe valvular disease, uncontrolled hypertension, CHF and chronic diseases. Results: 10 patients were enrolled in each group. The case group all had a positive sleep study for OSA and all control group patients had a Berlin score of 0. When compared, afib in OSA tend be permanent (mean duration 5 yrs vs. 1 yr; p ! 0.05), resistant to intervention (number of patients with 2 or more interventions; 9 vs. 1; p ! 0.05) and worsened oxidative stress profile. (mean EhGSH -118 6 6mV vs. -139 6 16mV; p 5 0.0038.) Mean values for EhCyS were not different. The number of patients on B blockers, ACE inhibitors and statins (known to alter oxidative stress) were not different. Conclusion: Our data suggest, OSA is associated with worsened oxidative stress and treatment resistance in AF. A significant proportion of elderly population have AF, aggressive evaluation for OSA in new onset afib population is paramount, as it is often under attended by both physicians and patients. Further studies are needed to evaluate the efficacy of treating OSA in afib and the possible role of oxidative stress treatment in this population.
196 Right Phrenic Nerve Stimulation for Apnea in Heart Failure Patients Using a Novel Intravenous Lead Ralph Augostini1, Dariusz Jagielski2, Xilong Zhang3, Shi-Jiang Zhang3, Dariusz Michalkiewicz4, Randy Westlund5; 1The Ohio State University Medical Center, Columbus, OH; 24th Military Hospital, Wroclaw, Poland; 3Jiangsu Province Hospital, Nanjing, China; 4Central Military Hospital, Warsaw, Poland; 5Cardiac Concepts, Minnetonka, MN Introduction: Treatment of sleep disordered breathing (SDB) in heart failure (HF) patients (pts) may improve their HF status. Stimulation of the phrenic nerve (PN) via surgically implanted cuff electrodes has been shown to be effective in modulating respiratory function. Unilateral transvenous stimulation of the PN may allow for treatment of SDB in HF patients. Methods: The right brachiocephalic vein (BCV) was selectively engaged and a venogram performed in pts with HF (mean NYHA Class 2.4) and SDB. Multipolar leads were inserted into the right BCV. Acute stability was assessed using deep breathing and coughing maneuvers under fluoroscopic observation. Stimulation thresholds (ST) were measured in the most stable locations available. Leads remained in situ for a 2-night SDB therapy study. Results: Ten pts. underwent venous access and venography of the right BCV. The lead was deployed into the BCV and electrodes oriented relative the PN in 10-45 minutes. In all pts a position was found that was stable while the patient coughed and performed deep respiration repeatedly. Extra-respiratory sensation (ERS) including shoulder twitch was observed in 1 pt. ERS was successfully mitigated by stimulating from a different electrode pair. No adverse events were observed. Observed Stimulation Thresholds N
Pulse Width (msec)
ST (mA)
Impedance (U)
5 4 1
150 240 300
4.9 6 1.1 4.3 6 0.8 4.0
360 6 71 327 6 71 n/a
Conclusion: Stable acute transvenous stimulation of the phrenic nerve via the right brachiocephalic vein is feasible and well-tolerated. Unilateral right phrenic nerve stimulation is possible without extra-respiratory sensations and may be a basis of treatment for periodic breathing in heart failure patients.
197 Can Disease Etiology Predict Differences in Intra-Ventricular Conduction Delay in CRT patients? Nader Ghaly1, Mary Tiernan1, David Muller2; 1Electrophysiology, AtlatiCare Regional Medical Center, Pomona, NJ; 2CRM, St Jude, Sylmar, CA Introduction: Differences in response to cardiac resynchronization therapy (CRT) can vary depending on disease etiology. It has been suggested that this may be due to alterations in conduction velocities in the ventricle. These changes may be to to the presence or abscence of myocaridal scar formation. Methods: We evaluated retrospective implant data from patients undergoing CRTD implants between 2007 and 2008.(N 5 107) These patients were then divided based on disease etiology into 2 groups, Ischemic (ICM) and Non-Ischemic (NICM) (N 5 86 and 31 respectively)