LV dysfunction and pulmunary congestion in dialysis patients F. - - PowerPoint PPT Presentation
Cagliari 30 aprile 3 maggio 2011 LV dysfunction and pulmunary congestion in dialysis patients F. Mallamaci Death rate (1 year) Death rate (1 year) % % % % 100 100 100 100 ESRD ESRD SIN registry SIN registry X 5 10 10 10 10
X 350
X 5
Courtesy of Massimo Cirillo 2006 Courtesy of Massimo Cirillo 2006
(1 year)
LV systolic dysfunction: LV systolic dysfunction: ∼ ∼40% 40% LV diastolic dysfunction: LV diastolic dysfunction: ∼ ∼100% 100% Why the risk of cardiac disease is so high in Why the risk of cardiac disease is so high in ESRD? ESRD? How this risk is generated? How this risk is generated?
4 4 3 3 2 2 1 1
ml/min ml/min
1.4 2.0 2.0 2.8 2.8 3.4 3.4 1.0 1.0 60< 60< 45 45 3aCKD 3aCKD 30 30 3bCKD 3bCKD 15 15 4CKD 4CKD 5CKD 5CKD
Go AS, New Engl J Med. 351: 1296; 2004 Go AS, New Engl J Med. 351: 1296; 2004 1.120.295 individuals, follow up 2.8 years 1.120.295 individuals, follow up 2.8 years REFERENCE REFERENCE
REFERENCE REFERENCE REFERENCE Emerging risk factors
Inflammation Inflammation ⇑ ⇑ Sympathetic activity Sympathetic activity ⇑ ⇑ Asymmetric Dimethyl Arginine (ADMA) Asymmetric Dimethyl Arginine (ADMA)
Old age Old age
The GFR captures the The GFR captures the prognostic value of these prognostic value of these non non-
Framingham risk factors factors
Volume expansion Volume expansion
⇑ ⇑Cholesterol Cholesterol ⇑ ⇑ Glucose/Diabetes Glucose/Diabetes
risk factors peculiar to CKD risk factors peculiar to CKD
Anemia Anemia ⇑ ⇑P P ⇑ ⇑PTH PTH
Why volume expansion is so Why volume expansion is so difficult to control in the difficult to control in the modern dialysis era when UF modern dialysis era when UF technology allows precise and technology allows precise and effective volume removal effective volume removal profiling? profiling?
Extracellular Volume (sodium space) Extracellular Volume (sodium space) ∼ ∼16 16-
18 L Blood Volume Blood Volume ( (~30% extracellular volume) ~30% extracellular volume) 5.6 5.6L L
located in the vascular space , encompassing located in the vascular space , encompassing heart, aorta down to capillary bed and back to heart, aorta down to capillary bed and back to the venous system the venous system . .
8 8-
10 mmHg
Cardiac Extracellular Fluids Cardiac Extracellular Fluids function Volume function Volume
variable space, depending on vascular tone and compliance and compliance
In reality fluids volume is In reality fluids volume is
Capillary Pressure at Capillary Pressure at alveolar level alveolar level
Atrial Pressure Atrial Pressure LV Diastolic (filling) LV Diastolic (filling) Pressure Pressure
Capillary Wedge Pressure Capillary Wedge Pressure a very reliable indicator of a very reliable indicator of LV filling pressure LV filling pressure
However highly reliable, However highly reliable, this is an invasive this is an invasive technique and therefore it technique and therefore it is employed in the acute is employed in the acute setting only. setting only.
which depends on 2 components: which depends on 2 components: 1) volume 2) LV function component . 1) volume 2) LV function component . Therefore it reflects the loading conditions of the Therefore it reflects the loading conditions of the LV at a given Blood Volume LV at a given Blood Volume
Capillary Pressure at Capillary Pressure at alveolar level alveolar level Pulmonary Water Pulmonary Water Pulmonary edema Pulmonary edema Lung comets Lung comets ! the number of lung comets is strictly ! the number of lung comets is strictly proportional to lung water proportional to lung water
Lung water
CHEST CHEST
127:1690, 2005 127:1690, 2005
Severe lung Severe lung congestion congestion Moderate lung Moderate lung congestion congestion <14 14 <14 14-
30 >30 Lung Comets number Lung Comets number Prevalence Prevalence (%) (%) 50 50 40 40 30 30 20 20 10 10 35% 35% 28% 28% Hypo Normal Hyper Hypo Normal Hyper Hydration Status by BIA Hydration Status by BIA Lung Comets Lung Comets (n) (n) 60 60 50 50 40 40 30 30 20 20 10 10 17 17 20 20 15 15
Detection of pulmonary congestion by chest ultrasound (US) in dialysis patients. Mallamaci F, Benedetto A, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C 3;586; 2010
Useful in Dialysis patients? Useful in Dialysis patients? an inclusive study: All but 3 patients of a large dialysis unit an inclusive study: All but 3 patients of a large dialysis unit (n=78). (n=78). Lung comets, BIA, echocardiography measured pre and post Lung comets, BIA, echocardiography measured pre and post-
dialysis
The lack of association with hydration The lack of association with hydration status indicates that in this population LV status indicates that in this population LV dysfunction is the fundamental driver of dysfunction is the fundamental driver of lung congestion in ESRD. lung congestion in ESRD.
Pulmonary Pressure Pulmonary Pressure (mmHg) (mmHg)
Left atrial Volume Left atrial Volume
r=0.33, P=0.002
70 60 50 40 30 20 10 200 150 100 50
Lung comets (n)
r=0.39, P<0.001
30 25 20 15 10 5
(mL/m2.7)
200 150 100 50
Lung comets (n)
r=-0.73, P<0.001
80 70 60 50 40 30 20 10 200 150 100 50
Lung comets (n)
Detection of pulmonary congestion by chest ultrasound (US) in dialysis patients. Mallamaci F, Benedetto A, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C 3:586 ; 2010
LV Ejection LV Ejection Fraction (%) Fraction (%)
Detection of pulmonary congestion by chest ultrasound (US) in dialysis patients. Mallamaci F, Benedetto A, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C 3:586; 2010 Severe lung Severe lung congestion congestion Moderate lung Moderate lung congestion congestion <14 14 <14 14-
30 >30 Lung Comets number Lung Comets number Prevalence Prevalence (%) (%) 50 50 40 40 30 30 20 20 10 10 33% 33% 30% 30%
Pulmonary Pressure Pulmonary Pressure (mmHg) (mmHg)
Left atrial Volume Left atrial Volume
r=0.32, P=0.006
70 60 50 40 30 20 10 200 150 100 50
Lung comets (n)
30 25 20 15 10 5
(mL/m2.7)
200 150 100 50
Lung comets (n)
r=-0.64, P<0.001
80 70 60 50 40 30 20 10 200 150 100 50
Lung comets (n)
Detection of pulmonary congestion by chest ultrasound (US) in dialysis patients. Mallamaci F, Benedetto A, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C 3:586 ; 2010
LV Ejection LV Ejection Fraction (%) Fraction (%)
r=0.30, P=0.01
200 180 160 140 120 100 80 60 40 20
Pre-dialysis lung comets (n)
140 120 100 80 60 40 20
Lung comets changes (n)
r=0.75 P<0.001
Detection of pulmonary congestion by chest ultrasound (US) in dialysis patients. Mallamaci F, Benedetto A, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C 3:586; 2010
Lung comets changes are directly associate to the number of Lung comets changes are directly associate to the number of comets before the dialysis session comets before the dialysis session .. ..
Peritoneal Dialysis Peritoneal Dialysis Volume expansion : often a major problem Volume expansion : often a major problem Hemodialysis Hemodialysis Peritoneal Dialysis Peritoneal Dialysis
n=201 n=201 n=51 n=51
Systolic BP Systolic BP mmHg mmHg 180 180 140 140 100 100 Left Atrial volume Left Atrial volume ml ml 80 80 60 60 40 40 20 20 90 90 70 70 50 50 30 30
LVH (%) 62% 62% 86% 86% P <0.001
PD patients obviously volume PD patients obviously volume expanded. expanded. A change in local clinical policies A change in local clinical policies clearly needed clearly needed
60% 60%
Systolic BP Systolic BP mmHg mmHg 180 180 140 140 100 100 90 90 70 70 50 50 30 30
LVH (%)
New policy New policy RC RC
Multiply efforts for educating patients at carefully Multiply efforts for educating patients at carefully monitoring BP on a daily basis to aim at GLs monitoring BP on a daily basis to aim at GLs recommended systolic BP target (<140 mmHg). recommended systolic BP target (<140 mmHg). Systematic use of icodextrin in patients in Systematic use of icodextrin in patients in whom BP is insufficiently controlled or with whom BP is insufficiently controlled or with clinical evidence of volume expansion. clinical evidence of volume expansion.
Clinical policies vary much across centres Clinical experience and background errors make a difference Peritoneal Dialysis Peritoneal Dialysis
Systolic BP Systolic BP mmHg mmHg 140 140 100 100 90 90 70 70 50 50 30 30
LVH (%)
New policy New policy RC RC
60% 60%
45 45 30 30 15 15 Systolic BP Systolic BP mmHg mmHg 140 140 100 100 90 90 70 70 50 50 30 30
LVH (%)
Centre Centre with less with less experience experience
57% 57%
Left atrium by the 10% larger
Different emphasis on volume Different emphasis on volume-
salt control may translate into
patients being treated in centres patients being treated in centres with less stringent salt with less stringent salt-
volume policies. policies. Lung comets monitoring may be Lung comets monitoring may be useful to achieve salt useful to achieve salt-
volume balance appropriate to individual balance appropriate to individual cardiac / hemodynamic profile cardiac / hemodynamic profile
+ 2SD
Average Concordance index=0.96, 95% CI: 0.90-0.98
Inter-observer agreement
60 40 20
[Lung comets (1st Obs)- Lung comets (2 nd Obs)]
200 150 100 50
[Lung comets (1st Obs)+ Lung comets (2nd Obs)]/2
Concordance index=0.98, 95% CI: 0.97-0.99
[Lung comets (3.5 MHz)+ Lung comets (3.0 MHz)]/2
100 80 60 40 20
[Lung comets (3.5 MHz) - Lung comets (3.0 MHz)]
15 10 5
Agreement between probes / machines
Lung US is a reliable technique for the measurement
pulmonary water in dialysis patients.
Lung comets monitoring may be Lung comets monitoring may be useful to achieve salt useful to achieve salt-
volume balance appropriate to individual balance appropriate to individual cardiac / hemodynamic profile cardiac / hemodynamic profile late eighties late eighties BIA bielectrical impedance analysis BIA bielectrical impedance analysis enthusiasm enthusiasm disappointement disappointement controversy controversy Lung US still to be appropriately Lung US still to be appropriately tested tested : :
Cohort studies
Clinical trials
Multicenter cohort study Multicenter cohort study 22 22 Nephrology and Dialysis Centers Nephrology and Dialysis Centers Enrollment started in April 2009 Enrollment started in April 2009
Modestly affected by adjustment for Framingham Risk factors and NYHA class
These preliminary analyses indicate that validating lung comets in a clinical trial would be worthwhile undertaking
Multicentric study N° 458 pts on dialysis Follow-up 400 days
Source
Cumulative risk of combined outcomes (%)
Combined outcome death, heart failure, anginal episodes, MI (initial analyses based on 63 events)
600 400 200 .3 .2 .1 0.0
Lung Comets <15 Lung Comets >45
HR: 3.03,
(95% CI: 1.58-5.81)
Lung Comets 16-45
10 leading research groups in Italy, France, 10 leading research groups in Italy, France, Germany, GB, Sweden, Spain, Poland, Greece, Germany, GB, Sweden, Spain, Poland, Greece, Romania, Turkey Romania, Turkey
& C
La congestione cardiopolmonare La congestione cardiopolmonare è è comune nei pazienti in dialisi e nella comune nei pazienti in dialisi e nella maggioranza dei casi maggioranza dei casi è è pauci o asintomatica. pauci o asintomatica. La semplice misura dei volumi liquidi non offre informazion La semplice misura dei volumi liquidi non offre informazioni rilevanti per i rilevanti per indirizzare le decisioni cliniche nei pazienti in dialisi. indirizzare le decisioni cliniche nei pazienti in dialisi. La misura dell La misura dell
acqua polmonare con gli US è è una tecnica promettente in una tecnica promettente in quanto fornisce informazioni affidabili sul grado di congestio quanto fornisce informazioni affidabili sul grado di congestione polmonare, ne polmonare, cio cioè è su un fenomeno da prevenire o correggere tempestivamente nei su un fenomeno da prevenire o correggere tempestivamente nei pazienti in dialisi. pazienti in dialisi. L L
utilità à di questa tecnica deve essere testata in uno specifico tri di questa tecnica deve essere testata in uno specifico trial al clinico. clinico.
coronary heart disease Heart failure Heart failure
Cerebrovascular Cerebrovascular disease disease
LC <15 LC 16-45 LC >45
1.0 0.9 0.8 0.7 800 700 600 500 400 300 200 100
Time (days)
Cumulative events free survival
Combined outcome death, heart failure, anginal episodes, MI
HR: 3.03,
(95% CI: 1.58-5.81)
Pulmonary Pressure Pulmonary Pressure (mmHg) (mmHg)
Left atrial Volume Left atrial Volume
r=0.33, P=0.002 r=0.32, P=0.006
70 60 50 40 30 20 10 200 150 100 50
Lung comets (n)
r=0.39, P<0.001 r=0.30, P=0.01
30 25 20 15 10 5
(mL/m2.7)
200 150 100 50
Lung comets (n)
r=-0.73, P<0.001 r=-0.64, P<0.001
80 70 60 50 40 30 20 10 200 150 100 50
Lung comets (n)
Detection of pulmonary congestion by chest ultrasound (US) in dialysis patients. Mallamaci F, Benedetto A, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C 3:586 ; 2010
LV Ejection LV Ejection Fraction (%) Fraction (%)
Extracellular Volume (sodium space) Extracellular Volume (sodium space)
8 8-
10 mmHg
kidney is central in regulating the kidney is central in regulating the blood volume blood volume
LV filling pressure relationship relationship
100 100 80 80 60 60 40 40 20 20
Clinical policies adopted in Tassin make a difference Tassin make a difference . .
1.5 1.5 1.4 1.4 1.3 1.3 1.2 1.2 1.1 1.1 1.0 1.0 0.8 0.8
0.5-1.0 1.0-1.5 1.5-2.0 2.5-3.0 3.0-3.5 3.5-4.0 >4.0 Kg. 2.0-2.5
High body weight gain, High body weight gain, Better appetite and nutrition status! Better appetite and nutrition status! Adjusted for malnutrition/inflammation Adjusted for malnutrition/inflammation
% % 100 100 10 10 1 1 0.1 0.1 0.01 0.01 25 25-
34 45-
54 65-
74 >85 Age (years Age (years)
General population General population
X X 500
X X 5
Annual mortality for CV diseases Annual mortality for CV diseases