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Clinical Predictors of Mortality and Outcomes in Patients with Transthyretin Cardiac Amyloidosis
S50 Journal of Cardiac Failure Vol. 19 No. 8S August 2013
Epidemiology, Prevention 140
142
Clinical Predictors of Mortality and Outcomes in Patients with Transthyretin Cardiac Amyloidosis David Tsay1, Jeff Goldsmith2, Mathew Maurer1; 1Columbia University Medical Center, New York, NY; 2Columbia Mailman School of Public Health, New York, NY
Acute Effects of Adaptive Servo-Ventilation on Hemodynamics in Advanced Chronic Heart Failure Patients Michinari Hieda1, Yoshihiro Murata1, Osamu Seguchi1, Masanobu Yanase1, Takuma Sato1, Haruki Sunami1, Takuya Watanabe1, Toshiaki Shishido2, Takeshi Nakatani1; 1 National Cerebral and Cardiovascular Center, Suita, Osaka, Japan; 2National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Background: Cardiac transthyretin amyloidosis (ATTR) is a progressive condition that results in a restrictive cardiomyopathy with congestive heart failure. There are few studies to date which examine the predictors of clinical outcomes and mortality of patients with this fatal disease. Methods: In a cohort of ATTR patients (n591 age 7269.8 years, 85% male) referred to Columbia University Medical Center between 2001-2013, we examined the clinical predictors for outcomes such as death, hospitalizations, and arrhythmia. We performed survival analysis using Cox-Proportional Hazard modeling to identify baseline predictors of death. Results: Patients within our ATTR cohort on average had mild systolic dysfunction (avg LVEF 41% +/17%), elevated troponin (avg 0.18 +/- 0.41 ng/mL), and elevated BNP levels (807 +/- 617 pg/ml). Initial analyses show that univariate predictors of death include serum biomarkers (BNP O 600 pg/ml, HR 2.77 p 5 0.025; Troponin O 0.1 ng/mL, HR 2.76, p 5 0.026), decreased renal function (eGFR ! 30 ml/min/m2, HR 3.99, p ! 0.001), and modified BMI (BMI x albumin ! 100 (kg*g)/(m2*dL), HR 2.4, p 5 0.04). Multivariate analysis suggest that mBMI and eGFR are independent predictors of mortality (HR 5.3 (95% CI 1.7 - 16.5) and 9.5 (95% CI 1.9-46.5) respectively, global LRT p-value ! 0.01). Conclusions: In this single center study of a relatively large cohort of subjects with ATTR cardiomyopathy in the United States, markers of renal function and nutritional state were stronger predictors of mortality than cardiac biomarkers.
141 Self-Regulation Training Remodels Autonomic Receptors in End-Stage Heart Failure Michael G. McKee1, Dana L. Schneeberger2, Wendy E. Sweet2, W.H. Wilson Tang3, Christine S. Moravec2; 1Cleveland Clinic, Cleveland, OH; 2Cleveland Clinic, Cleveland, OH; 3Cleveland Clinic, Cleveland, OH Heart failure (HF) is characterized by autonomic imbalance Sympathetic nervous system (SNS) input to the myocardium is augmented in response to decreased cardiac output, and several studies have suggested that parasympathetic nervous system (PNS) input may be correspondingly decreased Given the key role of autonomic regulation in cardiac physiology, drugs and devices have been developed which attempt to restore normal autonomic balance in HF Beta blockers have been the mainstay of SNS regulation, while vagal nerve stimulation is currently being tested in the INNOVATE trial with the hypothesis that it will prove beneficial by augmenting PNS input to the heart With data to suggest that PNS activation may be anti-inflammatory, the need for therapies which regulate PNS input is clear We have tested the hypothesis that teaching patients to regulate their own SNS / PNS balance will cause measurable change in clinical status and quality of life for patients with HF, and that it may further remodel the failing myocardium, similar to what we and others have shown for left ventricular assist device therapy We have previously reported that patients trained in self-regulation using biofeedback (BF) report better quality of life, and that a subset of patients show improvement in cardiovascular reactivity, six minute walk distance and plasma norepinephrine We have further demonstrated that muscles removed from the hearts of patients who have been taught BF skills show an improved inotropic response to beta adrenergic stimulation In the current study, we measured beta adrenergic receptors and muscarinic cholinergic receptors, using radioligand binding and Scatchard analysis, in the hearts of patients who completed BF training as compared to those who did not (F) and to non failing controls (NF) Data show differential effects on the two receptor populations Beta adrenergic receptors, effectors of the SNS, were decreased in failing hearts, and did not recover with BF training, despite recovery of the inotropic response in muscles from the same hearts Muscarinic receptors, cardiac effectors of the PNS, increased in patients with HF, and returned to non failing levels in patients who participated in BF training These data demonstrate that self-regulation training using BF is capable of causing remodeling of membrane receptors in the failing heart, but also suggest that the effect is greater on parasympathetic receptors as compared to sympathetic receptors.
Background: Advanced chronic heart failure (ACHF), the final stage of cardiovascular disease, is related to high mortality and poor prognosis. In ACHF patients, systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) are often elevated. Adaptive servo-ventilation (ASV) is a non-invasive method for positive pressure ventilation that automatically adjusts inspiratory pressure support for each breath and set at the low level of end-expiratory pressure. ASV was initially developed to treat patients with sleep-disordered breathing (SDB). Recently, several studies have indicated its therapeutic effect for patients with heart failure. We investigated the acute hemodynamic effects of ASV in ACHF patients. Methods: We measured hemodynamic parameters using right cardiac catheterization before, and 20 minutes after initiation of ASV therapy in 13 ACHF patients (dilated cardiomyopathy n510, dilated hypertrophic cardiomyopathy n53 ; mean age 41.2 years; 10 males; NYHA functional class III n52 or IV n511). All met the European Society of Cardiology Criteria for Advanced Chronic Heart Failure and received optimal medical therapy for at least 1 month, with catecholamine given as necessary before ASV therapy. ASV was applied using a full-face mask at default pressure settings (EEP, 5 cmH2O; inspiratory pressure support, 3-10 cmH2O). Results and Discussion: The acute effect of ASV was shown in Table. Following initiation of ASV, heart rate and respiratory rate were significantly decreased, and SpO2 and SvO2 were significantly increased. And also, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP), SVR, and PVR were significantly decreased. These results indicate that ASV leads to stabilize respiratory patterns in patients with ACHF, and this stability of respiratory patterns might cause the decrement of the sympathetic nerve activity and provide hemodynamic changes including the decreasing of PCWP, SVR and PVR. Conclusion: Our findings suggest that ASV may provide beneficial effects on hemodynamics in patients with ACHF. Table. Acute Effect of Adaptive Servo-Ventilation on Hemodynamics in Patients with Advanced Chronic Heart Failure
ASV 20 min
p value
6 6 6 6 6 6
14.9 1.94 1.22 8.61 9.37 10.2
0.011 0.0012 0.0015 0.012 0.38 0.16
* * * *
44.8 6 18.7
35.1 6 11.0
0.0018
*
22.6 6 10.2
18.5 6 8.13
0.0021
*
20.2 6 9.82
17.6 6 7.81
0.041
*
0.30 0.22 0.097 0.00016
*
0.0022
*
before Heart rate (bpm) Respiratory rate (/min) SpO2 [%] SvO2 [%] Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Systolic pulmonary artery pressure (mmHg) Diastolic pulmonary artery pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Right atrial pressure (mmHg) Cardiac output (L/min) Cardiac index (L/min/m2) Systemic vascular resistance (dyne/s/cm5) Pulmonary vascular resistance (dyne/s/cm5)
74.5 17.9 97.7 58.2 91.7 59.3
5.46 3.26 1.97 1789
6 6 6 6 6 6
6 6 6 6
20.7 2.99 1.6 12.9 10.9 13.2
4.31 0.96 441 441
319 6 172
69.0 13.5 99.0 63.3 91.8 57.8
5.23 3.33 2.08 1533
6 6 6 6
2.95 0.82 0.45 402
192 6 103
Data are presented as mean 6 SD.
143 Left Ventricular Outflow Impedance, Stroke Volume, and Syncope in Severe Aortic Stenosis with and without Systemic Arterial Hypertension Sachin Shah, Amit Kumar, Timothy Draper, William H. Gaasch; Lahey Clinic, Burlington, MA Introduction: The double-loaded ventricle, as seen in patients with the combination of severe aortic stenosis (AS) and hypertension (HTN), is associated with a variety of adverse clinical events. Our goal was to estimate the prevalence of syncope in AS patients with and without HTN and to search for hemodynamic mechanisms that might underlie syncope. Hypothesis: In patients with severe AS and a normal left ventricular (LV) ejection fraction (EF $ 50%), increased LV outflow impedance (i.e. systolic load in the pressure-volume plane) is more closely related to syncope than LV afterload-shortening relations (i.e. LV systolic wall stress - EF relations). Methods: Using a 2007 echocardiography database we identified 89 patients with
Epidemiology, Prevention 140
142
Clinical Predictors of Mortality and Outcomes in Patients with Transthyretin Cardiac Amyloidosis David Tsay1, Jeff Goldsmith2, Mathew Maurer1; 1Columbia University Medical Center, New York, NY; 2Columbia Mailman School of Public Health, New York, NY
Acute Effects of Adaptive Servo-Ventilation on Hemodynamics in Advanced Chronic Heart Failure Patients Michinari Hieda1, Yoshihiro Murata1, Osamu Seguchi1, Masanobu Yanase1, Takuma Sato1, Haruki Sunami1, Takuya Watanabe1, Toshiaki Shishido2, Takeshi Nakatani1; 1 National Cerebral and Cardiovascular Center, Suita, Osaka, Japan; 2National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Background: Cardiac transthyretin amyloidosis (ATTR) is a progressive condition that results in a restrictive cardiomyopathy with congestive heart failure. There are few studies to date which examine the predictors of clinical outcomes and mortality of patients with this fatal disease. Methods: In a cohort of ATTR patients (n591 age 7269.8 years, 85% male) referred to Columbia University Medical Center between 2001-2013, we examined the clinical predictors for outcomes such as death, hospitalizations, and arrhythmia. We performed survival analysis using Cox-Proportional Hazard modeling to identify baseline predictors of death. Results: Patients within our ATTR cohort on average had mild systolic dysfunction (avg LVEF 41% +/17%), elevated troponin (avg 0.18 +/- 0.41 ng/mL), and elevated BNP levels (807 +/- 617 pg/ml). Initial analyses show that univariate predictors of death include serum biomarkers (BNP O 600 pg/ml, HR 2.77 p 5 0.025; Troponin O 0.1 ng/mL, HR 2.76, p 5 0.026), decreased renal function (eGFR ! 30 ml/min/m2, HR 3.99, p ! 0.001), and modified BMI (BMI x albumin ! 100 (kg*g)/(m2*dL), HR 2.4, p 5 0.04). Multivariate analysis suggest that mBMI and eGFR are independent predictors of mortality (HR 5.3 (95% CI 1.7 - 16.5) and 9.5 (95% CI 1.9-46.5) respectively, global LRT p-value ! 0.01). Conclusions: In this single center study of a relatively large cohort of subjects with ATTR cardiomyopathy in the United States, markers of renal function and nutritional state were stronger predictors of mortality than cardiac biomarkers.
141 Self-Regulation Training Remodels Autonomic Receptors in End-Stage Heart Failure Michael G. McKee1, Dana L. Schneeberger2, Wendy E. Sweet2, W.H. Wilson Tang3, Christine S. Moravec2; 1Cleveland Clinic, Cleveland, OH; 2Cleveland Clinic, Cleveland, OH; 3Cleveland Clinic, Cleveland, OH Heart failure (HF) is characterized by autonomic imbalance Sympathetic nervous system (SNS) input to the myocardium is augmented in response to decreased cardiac output, and several studies have suggested that parasympathetic nervous system (PNS) input may be correspondingly decreased Given the key role of autonomic regulation in cardiac physiology, drugs and devices have been developed which attempt to restore normal autonomic balance in HF Beta blockers have been the mainstay of SNS regulation, while vagal nerve stimulation is currently being tested in the INNOVATE trial with the hypothesis that it will prove beneficial by augmenting PNS input to the heart With data to suggest that PNS activation may be anti-inflammatory, the need for therapies which regulate PNS input is clear We have tested the hypothesis that teaching patients to regulate their own SNS / PNS balance will cause measurable change in clinical status and quality of life for patients with HF, and that it may further remodel the failing myocardium, similar to what we and others have shown for left ventricular assist device therapy We have previously reported that patients trained in self-regulation using biofeedback (BF) report better quality of life, and that a subset of patients show improvement in cardiovascular reactivity, six minute walk distance and plasma norepinephrine We have further demonstrated that muscles removed from the hearts of patients who have been taught BF skills show an improved inotropic response to beta adrenergic stimulation In the current study, we measured beta adrenergic receptors and muscarinic cholinergic receptors, using radioligand binding and Scatchard analysis, in the hearts of patients who completed BF training as compared to those who did not (F) and to non failing controls (NF) Data show differential effects on the two receptor populations Beta adrenergic receptors, effectors of the SNS, were decreased in failing hearts, and did not recover with BF training, despite recovery of the inotropic response in muscles from the same hearts Muscarinic receptors, cardiac effectors of the PNS, increased in patients with HF, and returned to non failing levels in patients who participated in BF training These data demonstrate that self-regulation training using BF is capable of causing remodeling of membrane receptors in the failing heart, but also suggest that the effect is greater on parasympathetic receptors as compared to sympathetic receptors.
Background: Advanced chronic heart failure (ACHF), the final stage of cardiovascular disease, is related to high mortality and poor prognosis. In ACHF patients, systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) are often elevated. Adaptive servo-ventilation (ASV) is a non-invasive method for positive pressure ventilation that automatically adjusts inspiratory pressure support for each breath and set at the low level of end-expiratory pressure. ASV was initially developed to treat patients with sleep-disordered breathing (SDB). Recently, several studies have indicated its therapeutic effect for patients with heart failure. We investigated the acute hemodynamic effects of ASV in ACHF patients. Methods: We measured hemodynamic parameters using right cardiac catheterization before, and 20 minutes after initiation of ASV therapy in 13 ACHF patients (dilated cardiomyopathy n510, dilated hypertrophic cardiomyopathy n53 ; mean age 41.2 years; 10 males; NYHA functional class III n52 or IV n511). All met the European Society of Cardiology Criteria for Advanced Chronic Heart Failure and received optimal medical therapy for at least 1 month, with catecholamine given as necessary before ASV therapy. ASV was applied using a full-face mask at default pressure settings (EEP, 5 cmH2O; inspiratory pressure support, 3-10 cmH2O). Results and Discussion: The acute effect of ASV was shown in Table. Following initiation of ASV, heart rate and respiratory rate were significantly decreased, and SpO2 and SvO2 were significantly increased. And also, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP), SVR, and PVR were significantly decreased. These results indicate that ASV leads to stabilize respiratory patterns in patients with ACHF, and this stability of respiratory patterns might cause the decrement of the sympathetic nerve activity and provide hemodynamic changes including the decreasing of PCWP, SVR and PVR. Conclusion: Our findings suggest that ASV may provide beneficial effects on hemodynamics in patients with ACHF. Table. Acute Effect of Adaptive Servo-Ventilation on Hemodynamics in Patients with Advanced Chronic Heart Failure
ASV 20 min
p value
6 6 6 6 6 6
14.9 1.94 1.22 8.61 9.37 10.2
0.011 0.0012 0.0015 0.012 0.38 0.16
* * * *
44.8 6 18.7
35.1 6 11.0
0.0018
*
22.6 6 10.2
18.5 6 8.13
0.0021
*
20.2 6 9.82
17.6 6 7.81
0.041
*
0.30 0.22 0.097 0.00016
*
0.0022
*
before Heart rate (bpm) Respiratory rate (/min) SpO2 [%] SvO2 [%] Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Systolic pulmonary artery pressure (mmHg) Diastolic pulmonary artery pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Right atrial pressure (mmHg) Cardiac output (L/min) Cardiac index (L/min/m2) Systemic vascular resistance (dyne/s/cm5) Pulmonary vascular resistance (dyne/s/cm5)
74.5 17.9 97.7 58.2 91.7 59.3
5.46 3.26 1.97 1789
6 6 6 6 6 6
6 6 6 6
20.7 2.99 1.6 12.9 10.9 13.2
4.31 0.96 441 441
319 6 172
69.0 13.5 99.0 63.3 91.8 57.8
5.23 3.33 2.08 1533
6 6 6 6
2.95 0.82 0.45 402
192 6 103
Data are presented as mean 6 SD.
143 Left Ventricular Outflow Impedance, Stroke Volume, and Syncope in Severe Aortic Stenosis with and without Systemic Arterial Hypertension Sachin Shah, Amit Kumar, Timothy Draper, William H. Gaasch; Lahey Clinic, Burlington, MA Introduction: The double-loaded ventricle, as seen in patients with the combination of severe aortic stenosis (AS) and hypertension (HTN), is associated with a variety of adverse clinical events. Our goal was to estimate the prevalence of syncope in AS patients with and without HTN and to search for hemodynamic mechanisms that might underlie syncope. Hypothesis: In patients with severe AS and a normal left ventricular (LV) ejection fraction (EF $ 50%), increased LV outflow impedance (i.e. systolic load in the pressure-volume plane) is more closely related to syncope than LV afterload-shortening relations (i.e. LV systolic wall stress - EF relations). Methods: Using a 2007 echocardiography database we identified 89 patients with