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Hormonal Changes as a Potential Cause for Monthly Fluid Status Variation as Indicated by Intrathoracic Impedance
Heart, Lung and Circulation (2014) 23, 39–42 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2013.04.121
ORIGINAL ARTICLE
Hormonal Changes as a Potential Cause for Monthly Fluid Status Variation as Indicated by Intrathoracic Impedance John N. Makaryus, MD, Omid Javdan, DO, John N. Catanzaro, MD, Apoor Patel, MD, David Slotwiner, MD* Department of Cardiology, North Shore-Long Island Jewish Health System-Hofstra School of Medicine, New Hyde Park, NY 11040, United States Received 29 November 2012; received in revised form 26 April 2013; accepted 27 April 2013; online published-ahead-of-print 10 June 2013
Early detection of decompensated heart failure enables clinicians to tailor medical therapy to individual patient needs. The utility of transthoracic impedance assessment in the early diagnosis of volume overload has been documented in the literature. We describe the case of a young woman without congestive heart failure who was noted to have cyclical variations of transthoracic impedances that correlated with her menstrual cycle and discuss other factors that may confound proper diagnosis of volume overload in patients with implantable cardioverter-defibrillators. Keywords
Intrathoracic impedance Heart failure Hormonal changes Implantable cardioverter-defibrillator Menstrual cycle
Introduction Some implantable cardioverter defibrillators (ICD) with or without cardiac resynchronisation therapy (CRT) have the ability to continuously monitor heart rate variability, daily heart rate, and patient activity. Changes in these measurements have been associated with heart failure prognosis and prediction of acute heart failure events. As most ICDs are currently implanted for primary prevention of sudden cardiac death in patients with left ventricular dysfunction [1], early detection of impending heart failure exacerbation is important as the majority of patients who receive ICD’s are at risk. Transthoracic impedance has been shown to be a reliable marker of pulmonary congestion [2,3]. The Medtronic OptiVol Fluid Status Monitoring System is an FDA-approved algorithm that has been incorporated into some Medtronic ICDs to help in early detection of pulmonary vascular congestion and alert clinicians that intervention may be required to prevent repeat heart failure hospitalisations [3].
According to the most recent statistics from the American Heart Association, heart failure affects nearly 5.7 million Americans of all ages and is the cause of more annual hospital admissions than all forms of cancer combined. Clinical parameters such as daily weights are important to detect heart failure exacerbation but insufficient alone to prevent very high rates of re-hospitalisation (approaching 50%) during the six months following a heart failure hospital admission [4]. Given the enormity of these statistics, the Optivol fluid status monitoring system was devised by Medtronic engineers to assist clinicians in the management and prevention of gross volume overload in patients who have ICDs equipped with this software algorithm. We present the case of a patient with congenital long QT syndrome, recurrent syncope and normal left ventricular function who underwent defibrillator implantation for primary prevention of sudden cardiac death. Upon routine device interrogation, her Optivol system demonstrated regular monthly variations in transthoracic impedance coinciding with her menstrual period.
* Corresponding author. Tel.: +1 718 470 7330; fax: +1 516 562 1464., Emails: [email protected], [email protected] © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
40
J.N. Makaryus et al.
Figure 1 The patient’s Optivol fluid index tracing demonstrating fairly regular variation of the Optivol fluid indices over a 12 month period.
Case Presentation A 41 year-old female with type I Long QT Syndrome statuspost ICD implantation (Medtronic VirtuosoTM DR D154AWG) presented to her electrophysiologist’s office for a routine device check. The patient’s device had been implanted in 2005 after a work-up for recurrent malignant syncope revealed no evidence of structural heart disease, but Long QT Type 1 genotype. Her transthoracic echocardiogram was unremarkable revealing normal left ventricular systolic and diastolic dysfunction. When she returned for follow-up, it was noted that her transthoracic impedance levels cycled at near-monthly intervals. In addition, her weight had increased by approximately 2.7 kg since her prior visit just over a month earlier. Her thoracic impedance levels reached a monthly maximum of 73 V and a minimum of 60 V. Her Optivol fluid index varied between 0 and 50. This trend (as well as her weight) implied a temporary increase in overall fluid status followed by a swift decline. The patient reported that the dates indicative of increased overall fluid status correlated with the dates of her menstrual period which lasted approximately 4–5 days (Figs. 1–3).
Discussion Thoracic impedance is measured by electrical impulses that travel from the right ventricular lead to the implanted device.
The Medtronic Optivol fluid status monitoring system uses this electrical impulse vector to measure impedance across the thoracic cavity. Impedance is measured via the transmission of small amounts of alternating current between the RV lead tip and the device can, and the average daily value is the mean impedance of measurements taken every 20 min (64 times a day), usually between the hours of 12 pm and 5 pm daily. Each patient’s individual reference impedance is calculated based upon a reading taken 34 days post-implantation of the device to allow a certain degree of equilibration post-procedure. The OptiVol system converts the data obtained from transthoracic impedance into a fluid index value that makes assessment of daily fluid status compared to the reference point easier for clinicians [5]. Since blood has lower resistance than pulmonary tissue and air, the impedance measured across the thoracic cavity is decreased as more fluid accumulates in the thoracic cavity. Intrathoracic impedance has been shown to be inversely related to pulmonary capillary wedge pressure and general fluid balance [2,3]. Studies such as the MIDHeft and PARTNERS-HF trials have shown that impedance correlates with fluid status in heart failure patients, and that impedance decline precedes clinical symptoms [3,6–9]. These studies, and others, confirmed that a composite diagnostic score based upon parameters assessed by the Optivol device (fluid status, heart rate and heart rate variability, VT/VF therapy, AF burden)
Figure 2 Corresponding monthly alterations in thoracic impedance which clinically correlated to the patient’s menstrual cycle.
41
Hormonal changes and intrathoracic impedance
Figure 3 Optivol fluid index in a separate patient with no evidence of volume overload. There is minimal fluctuation in the fluid index and the value never approaches the patient’s reference baseline.
significantly augmented the ability to predict heart failure events. Nevertheless, while thoracic fluid accumulation in heart failure is the most common cause for a change in thoracic impedance, other physiologic changes have been known to cause changes in impedance and hence potentially confound accurate assessment of heart failure status. As expected, intrathoracic processes such as pleural/pericardial effusions and non-cardiogenic pulmonary congestion/ oedema can change thoracic impedance [2]. In worsening chronic obstructive pulmonary disease, the associated pulmonary hyperinflation can cause increased thoracic impedance [1]. Infectious processes such as pneumonia or empyema can also affect impedance and the changes in impedance associated with these processes are far less predictable than those attributable to transudative fluid alone. Other reported potentially important variables include respiratory infection [2], fluid shifts related to dialysis [10], diuretic use [2,11], pericardial and pleural effusions [3], anaemia [12], and device implantation site infection [2] among others. In our case, the monthly changes in thoracic impedance were most likely due to the physiologic effects of menstruation. The menstrual cycle and pregnancy are associated with hormonal level changes in progesterone, oestrogen/estradiol, and aldosterone which in turn are associated with peripheral oedema and changes in body weight. In pregnancy, there is a marked increase in circulating plasma and total blood volume relatively early on in gestation, and there has been a report of pregnancy as a potential cause of Optivol alterations that may mimic the volume overload associated with heart failure [13]. The mechanism of these changes during menstruation is not well understood and is thought to be secondary to either modifications in salt reabsorption at the nephron level or due to fluid shifts from the intravascular to the extravascular space. Studies have demonstrated that these hormonal changes (specifically progesterone) strongly
affect the renal haemodynamics and the renal tubular response to salt in menstruating women. Progesterone possibly acts as a competitive mineralocorticoid receptor antagonist due to its natriuretic hormone properties which leads to markedly reduced sodium reabsorption in the distal nephron. It is also thought to cause renal vasodilation which results in increased proximal sodium reabsorption. In addition, progesterone induced vasodilation and increased vessel permeability is likely responsible for the fluid shifts into the interstitial compartment in the periphery [14]. These changes are what likely contributed to the regular monthly variations in thoracic impedance that were noted in our patient.
Conclusion The Optivol system has been shown to play a constructive role in providing objective data to augment the subjective information gleaned from patient evaluation to help identify volume overload states earlier than would be possible with clinical assessment alone. A variety of conditions, including respiratory or device infections, pleural or pericardial effusions, pregnancy, and even menstruation, however, may confound accurate assessment of a patient’s true volume status. More research into how to utilise and improve current Optivol technology to distinguish these various disease states is necessary and may further assist in the diagnosis and management of heart failure.
Financial Disclosures None.
Disclaimers None.
42
J.N. Makaryus et al.
References [1] Wilde AAM, Simmers TA. Primary prevention with ICDs, are we on the right track? Neth Heart J 2009;17(March (3)):92–4. [2] Yu CM, Wang L, Chau E, Chan RH, Kong SL, Tang MO, et al. Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalisation. Circulation 2005;112(August 9 (6)):841–8. [3] Wang L. Fundamentals of intrathoracic impedance monitoring in heart failure. Am J Cardiol 2007;99(May 21 (10A)):3G–10G. [4] Jencks SF, Williams MV, Coleman EA. Rehospitalisations among patients in the medicare fee-for-service program. N Engl J Med 2009;360(April 2 (14)):1418–28. [5] Medtronic VirtuosoR DR/VR ICD and ConcertoR and InSync SentryR CRT-D System Reference Guides. [6] Bourge RC, Abraham WT, Adamsn PB, Aaron MF, Aranda JM, Magalski A, et al. The COMPASS-HF study. JACC 2008;51:11. [7] Whellan DJ, Ousdigian KT, Al-Khatib SM, Pu W, Sarkar S, Porter CB, et al. PARTNERS study investigators, combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalisations: results from PARTNERS HF (program to access and review trending information and evaluate correlation to symptoms in patients with heart failure) study. J Am Coll Cardiol 2010;55(April 27 (17)):1803–10. [8] Vollmann D, Nagele H, Schauerte P, Wiegand U, Butter C, Zanotto G, et al. Clinical utility of intrathoracic impedance monitoring to alert
[9]
[10]
[11]
[12]
[13]
[14]
patients with an implanted device of deteriorating chronic heart failure. Eur Heart J 2007;28:1835–40. Conraads VM, Tavazzi L, Santini M, Oliva F, Gerritse B, Yu C, et al. Sensitivity and positive predictive value of implantable intrathoracic impedance monitoring as a predictor of heart failure hospitalisations: the SENSE-HF trial. Eur Heart J 2011;32(Sep (18)):2266–73. Dialysis Patient Case Courtesy of David Martin, MD, Cardiology Consultants, Medford, OR. 2006 Medtronic Inc., data on file, UC200601357 EN. Yu CM, Wang L, Chau E, Chan RH, Kong SL, Tang MO, et al. Correlation of device-based intra-thoracic impedance and patient fluid status during intravenous diuretic therapy in acute CHF. Eur Heart J 2002;23(Suppl.):158 [abstract]. Small R, Tang W, Wickemeyer W, Germany R, Hoppe B, Andriulli J, et al. Managing heart failure patients with intra-thoracic impedance monitoring: a multi-center US evaluation. J Card Fail 2007;13(August 6 (Suppl. 2)):S113–4. Kramer DB, Maisel WH. An unusual cause of abnormal intrathoracic impedance in a patient with arrhythmogenic right ventricular cardiomyopathy. Pacing Clin Electrophysiol 2011;34(7):60–3. Pechere-Bertschi A, Maillard M, Stalder H, Brunner HR, Burnier M. Renal segmental tubular response to salt during the normal menstrual cycle. Kidney Int 2002;61:425–31.
ORIGINAL ARTICLE
Hormonal Changes as a Potential Cause for Monthly Fluid Status Variation as Indicated by Intrathoracic Impedance John N. Makaryus, MD, Omid Javdan, DO, John N. Catanzaro, MD, Apoor Patel, MD, David Slotwiner, MD* Department of Cardiology, North Shore-Long Island Jewish Health System-Hofstra School of Medicine, New Hyde Park, NY 11040, United States Received 29 November 2012; received in revised form 26 April 2013; accepted 27 April 2013; online published-ahead-of-print 10 June 2013
Early detection of decompensated heart failure enables clinicians to tailor medical therapy to individual patient needs. The utility of transthoracic impedance assessment in the early diagnosis of volume overload has been documented in the literature. We describe the case of a young woman without congestive heart failure who was noted to have cyclical variations of transthoracic impedances that correlated with her menstrual cycle and discuss other factors that may confound proper diagnosis of volume overload in patients with implantable cardioverter-defibrillators. Keywords
Intrathoracic impedance Heart failure Hormonal changes Implantable cardioverter-defibrillator Menstrual cycle
Introduction Some implantable cardioverter defibrillators (ICD) with or without cardiac resynchronisation therapy (CRT) have the ability to continuously monitor heart rate variability, daily heart rate, and patient activity. Changes in these measurements have been associated with heart failure prognosis and prediction of acute heart failure events. As most ICDs are currently implanted for primary prevention of sudden cardiac death in patients with left ventricular dysfunction [1], early detection of impending heart failure exacerbation is important as the majority of patients who receive ICD’s are at risk. Transthoracic impedance has been shown to be a reliable marker of pulmonary congestion [2,3]. The Medtronic OptiVol Fluid Status Monitoring System is an FDA-approved algorithm that has been incorporated into some Medtronic ICDs to help in early detection of pulmonary vascular congestion and alert clinicians that intervention may be required to prevent repeat heart failure hospitalisations [3].
According to the most recent statistics from the American Heart Association, heart failure affects nearly 5.7 million Americans of all ages and is the cause of more annual hospital admissions than all forms of cancer combined. Clinical parameters such as daily weights are important to detect heart failure exacerbation but insufficient alone to prevent very high rates of re-hospitalisation (approaching 50%) during the six months following a heart failure hospital admission [4]. Given the enormity of these statistics, the Optivol fluid status monitoring system was devised by Medtronic engineers to assist clinicians in the management and prevention of gross volume overload in patients who have ICDs equipped with this software algorithm. We present the case of a patient with congenital long QT syndrome, recurrent syncope and normal left ventricular function who underwent defibrillator implantation for primary prevention of sudden cardiac death. Upon routine device interrogation, her Optivol system demonstrated regular monthly variations in transthoracic impedance coinciding with her menstrual period.
* Corresponding author. Tel.: +1 718 470 7330; fax: +1 516 562 1464., Emails: [email protected], [email protected] © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
40
J.N. Makaryus et al.
Figure 1 The patient’s Optivol fluid index tracing demonstrating fairly regular variation of the Optivol fluid indices over a 12 month period.
Case Presentation A 41 year-old female with type I Long QT Syndrome statuspost ICD implantation (Medtronic VirtuosoTM DR D154AWG) presented to her electrophysiologist’s office for a routine device check. The patient’s device had been implanted in 2005 after a work-up for recurrent malignant syncope revealed no evidence of structural heart disease, but Long QT Type 1 genotype. Her transthoracic echocardiogram was unremarkable revealing normal left ventricular systolic and diastolic dysfunction. When she returned for follow-up, it was noted that her transthoracic impedance levels cycled at near-monthly intervals. In addition, her weight had increased by approximately 2.7 kg since her prior visit just over a month earlier. Her thoracic impedance levels reached a monthly maximum of 73 V and a minimum of 60 V. Her Optivol fluid index varied between 0 and 50. This trend (as well as her weight) implied a temporary increase in overall fluid status followed by a swift decline. The patient reported that the dates indicative of increased overall fluid status correlated with the dates of her menstrual period which lasted approximately 4–5 days (Figs. 1–3).
Discussion Thoracic impedance is measured by electrical impulses that travel from the right ventricular lead to the implanted device.
The Medtronic Optivol fluid status monitoring system uses this electrical impulse vector to measure impedance across the thoracic cavity. Impedance is measured via the transmission of small amounts of alternating current between the RV lead tip and the device can, and the average daily value is the mean impedance of measurements taken every 20 min (64 times a day), usually between the hours of 12 pm and 5 pm daily. Each patient’s individual reference impedance is calculated based upon a reading taken 34 days post-implantation of the device to allow a certain degree of equilibration post-procedure. The OptiVol system converts the data obtained from transthoracic impedance into a fluid index value that makes assessment of daily fluid status compared to the reference point easier for clinicians [5]. Since blood has lower resistance than pulmonary tissue and air, the impedance measured across the thoracic cavity is decreased as more fluid accumulates in the thoracic cavity. Intrathoracic impedance has been shown to be inversely related to pulmonary capillary wedge pressure and general fluid balance [2,3]. Studies such as the MIDHeft and PARTNERS-HF trials have shown that impedance correlates with fluid status in heart failure patients, and that impedance decline precedes clinical symptoms [3,6–9]. These studies, and others, confirmed that a composite diagnostic score based upon parameters assessed by the Optivol device (fluid status, heart rate and heart rate variability, VT/VF therapy, AF burden)
Figure 2 Corresponding monthly alterations in thoracic impedance which clinically correlated to the patient’s menstrual cycle.
41
Hormonal changes and intrathoracic impedance
Figure 3 Optivol fluid index in a separate patient with no evidence of volume overload. There is minimal fluctuation in the fluid index and the value never approaches the patient’s reference baseline.
significantly augmented the ability to predict heart failure events. Nevertheless, while thoracic fluid accumulation in heart failure is the most common cause for a change in thoracic impedance, other physiologic changes have been known to cause changes in impedance and hence potentially confound accurate assessment of heart failure status. As expected, intrathoracic processes such as pleural/pericardial effusions and non-cardiogenic pulmonary congestion/ oedema can change thoracic impedance [2]. In worsening chronic obstructive pulmonary disease, the associated pulmonary hyperinflation can cause increased thoracic impedance [1]. Infectious processes such as pneumonia or empyema can also affect impedance and the changes in impedance associated with these processes are far less predictable than those attributable to transudative fluid alone. Other reported potentially important variables include respiratory infection [2], fluid shifts related to dialysis [10], diuretic use [2,11], pericardial and pleural effusions [3], anaemia [12], and device implantation site infection [2] among others. In our case, the monthly changes in thoracic impedance were most likely due to the physiologic effects of menstruation. The menstrual cycle and pregnancy are associated with hormonal level changes in progesterone, oestrogen/estradiol, and aldosterone which in turn are associated with peripheral oedema and changes in body weight. In pregnancy, there is a marked increase in circulating plasma and total blood volume relatively early on in gestation, and there has been a report of pregnancy as a potential cause of Optivol alterations that may mimic the volume overload associated with heart failure [13]. The mechanism of these changes during menstruation is not well understood and is thought to be secondary to either modifications in salt reabsorption at the nephron level or due to fluid shifts from the intravascular to the extravascular space. Studies have demonstrated that these hormonal changes (specifically progesterone) strongly
affect the renal haemodynamics and the renal tubular response to salt in menstruating women. Progesterone possibly acts as a competitive mineralocorticoid receptor antagonist due to its natriuretic hormone properties which leads to markedly reduced sodium reabsorption in the distal nephron. It is also thought to cause renal vasodilation which results in increased proximal sodium reabsorption. In addition, progesterone induced vasodilation and increased vessel permeability is likely responsible for the fluid shifts into the interstitial compartment in the periphery [14]. These changes are what likely contributed to the regular monthly variations in thoracic impedance that were noted in our patient.
Conclusion The Optivol system has been shown to play a constructive role in providing objective data to augment the subjective information gleaned from patient evaluation to help identify volume overload states earlier than would be possible with clinical assessment alone. A variety of conditions, including respiratory or device infections, pleural or pericardial effusions, pregnancy, and even menstruation, however, may confound accurate assessment of a patient’s true volume status. More research into how to utilise and improve current Optivol technology to distinguish these various disease states is necessary and may further assist in the diagnosis and management of heart failure.
Financial Disclosures None.
Disclaimers None.
42
J.N. Makaryus et al.
References [1] Wilde AAM, Simmers TA. Primary prevention with ICDs, are we on the right track? Neth Heart J 2009;17(March (3)):92–4. [2] Yu CM, Wang L, Chau E, Chan RH, Kong SL, Tang MO, et al. Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalisation. Circulation 2005;112(August 9 (6)):841–8. [3] Wang L. Fundamentals of intrathoracic impedance monitoring in heart failure. Am J Cardiol 2007;99(May 21 (10A)):3G–10G. [4] Jencks SF, Williams MV, Coleman EA. Rehospitalisations among patients in the medicare fee-for-service program. N Engl J Med 2009;360(April 2 (14)):1418–28. [5] Medtronic VirtuosoR DR/VR ICD and ConcertoR and InSync SentryR CRT-D System Reference Guides. [6] Bourge RC, Abraham WT, Adamsn PB, Aaron MF, Aranda JM, Magalski A, et al. The COMPASS-HF study. JACC 2008;51:11. [7] Whellan DJ, Ousdigian KT, Al-Khatib SM, Pu W, Sarkar S, Porter CB, et al. PARTNERS study investigators, combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalisations: results from PARTNERS HF (program to access and review trending information and evaluate correlation to symptoms in patients with heart failure) study. J Am Coll Cardiol 2010;55(April 27 (17)):1803–10. [8] Vollmann D, Nagele H, Schauerte P, Wiegand U, Butter C, Zanotto G, et al. Clinical utility of intrathoracic impedance monitoring to alert
[9]
[10]
[11]
[12]
[13]
[14]
patients with an implanted device of deteriorating chronic heart failure. Eur Heart J 2007;28:1835–40. Conraads VM, Tavazzi L, Santini M, Oliva F, Gerritse B, Yu C, et al. Sensitivity and positive predictive value of implantable intrathoracic impedance monitoring as a predictor of heart failure hospitalisations: the SENSE-HF trial. Eur Heart J 2011;32(Sep (18)):2266–73. Dialysis Patient Case Courtesy of David Martin, MD, Cardiology Consultants, Medford, OR. 2006 Medtronic Inc., data on file, UC200601357 EN. Yu CM, Wang L, Chau E, Chan RH, Kong SL, Tang MO, et al. Correlation of device-based intra-thoracic impedance and patient fluid status during intravenous diuretic therapy in acute CHF. Eur Heart J 2002;23(Suppl.):158 [abstract]. Small R, Tang W, Wickemeyer W, Germany R, Hoppe B, Andriulli J, et al. Managing heart failure patients with intra-thoracic impedance monitoring: a multi-center US evaluation. J Card Fail 2007;13(August 6 (Suppl. 2)):S113–4. Kramer DB, Maisel WH. An unusual cause of abnormal intrathoracic impedance in a patient with arrhythmogenic right ventricular cardiomyopathy. Pacing Clin Electrophysiol 2011;34(7):60–3. Pechere-Bertschi A, Maillard M, Stalder H, Brunner HR, Burnier M. Renal segmental tubular response to salt during the normal menstrual cycle. Kidney Int 2002;61:425–31.