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Co-operative expression of hemeoxygenase-1 and nitric oxide synthase gene expression in human dilated cardiomyopathy
Heart, Lung and Circulation
48th Annual Scientific Meeting of CSANZ
2000; 9
OUTCOME IN PATIENTS PARTICIPATING M A PILOT HEART FAILURE CLINIC. S Nicholls*, K Inder, J Lowe, B Bastian, P Candlish, J Holliday and D O’Connell. John Hunter Hospital, Newcastle. Background: Heart failme clinics optimise medical therapy and focus on lifestyle modifications and exercise. The aim of the study was to compare the outcome of patients participating in the clinic with those who refused or were excluded and a cohort of patients admitted with heart failure in 1993. Method: 183 patients were admitted over a 5 month period in 1998 with heart failure. Patients were invited to attend a clinic on discharge involving a home visit, 3 outpatient visits, rehabilitation sessions and an optional exercise pqramme. Clinical data and outcome were recorded. Results: 59 patients participated in the clinic. 50 refused and 74 were excluded. 54% of patients in the clinic group were male and mean age in the clinic group was 71 years (46-98). Patients who refused or were excluded were more likely to be female (64%) and were older with a mean age 79 years (60-95). In comparison to the 1993 cohort, clinic patients were more likely to receive an ACE inhibitor OI angiotensin II blocker (93% v 66%), beta blocker (30% v 6%), diuretics (97% v 71%) and digoxin (63% v 45%). Aspirin (67% v 37%) and warfain (17% v 10%) use was also greater in the clinic group. Clinic patients were less likely to receive calcium antagonists (10% v 24%). 28 day unplanned admission and mortality at 28 days and 12 months are listed in the following table. 1 28DAY 1 28DAY 1 12MON 1 I
~1
Conclusion: An increase in auummiate therapy for patients with heart failure resulted in improved unplan&d r&mission-& l&e change in mortality. Whilst the group who attended the clinic appeared to benefit in terms of reduced mortality and unplanned hospital r&missions, the results may suggest that those patients who are too unwell to take part have a worse outcome.
CHANGES IN TREATMENT AND STATUS OF PATIENTS AFTER ATTENDING A QUATERNARY REFERRAL HEART FAILURE CLINIC. andone*. T Yw MMBwdeich. Heart Failure Unit DepartmntofCanliology. ConcordHospital. Concord NSW. Patients with heart failure are becoming mxe common. complex and unwell requiring frequent homital admissions and multiple medications. Heart failure patients may achieve better out&me iftmna~ed in a Heat F&lure Clinic. We evaluated cha!.&s made to &tmnt of Heart Failure Clinic patients to assess its impact. METHOD: Analysed prior therapy of patients seen in a ouatentm referral Heart Failure Clinic over the past year to determine changu made to managkment. dESULTS: Assessed all 74 patients referred in the part year, aie 68*13 years, 77% male, New York Heart Association (NYHA) class 2.66i0.8 units, 46% ischaemic/54% non-ischaemic heart failure. Left ventricular (LV) ejection fraction was 026iO. 15units, LV end-diastolic diameter64~11 mm LV end-systolic diameter 53fl4 mm and left atria1 diameter 46i8 mm. All calcium channel blocking agents. tricyclic antidepressants and most non-steroidal anti-inflammatory agents were ceased 14% were enrolledinto clinical trials. No medications rose from 5.44kZ.Si to6.77*2.68/day. Changes were: MEDICATION BASELINE FOLLOW-UP ACE INHIBITORS (Angiotcnsin Converting Enzyme) 62% 62% 87 (-EQUMG’DAW 74 DIURETICS 70% 73% 58 @RUS~&UNALEbiTMC&‘DAY) 65 DIGOXIN 32% 34% 113 196 WSE (MO BETA- BLOCKERS 19% 65% (CARVEDlLOL~UIV~MC’DAY) 18 42 SPIRONOLACTONE 15% 43% 30 25 ~.=w3 ANGIOTENSIN ANTAGONISTS 20% 11% (CANDESARTANFQUtV~MCVDAY) 8 11 AMIODARONE 18% 26% 185 137 JJ3.v o”k!) NITRATES 31% 46% (BOSORBIDE MONONI’IRATB EQUNALRNT MG’DAy) 104 85 HYDRALAZINE 7% 8% 63 43 DOSE ms) WARFARIN 24% 24% ASPIRIN 43% 42% 142 131 DOSE MS) CHOLESTEROL LOWERING AGENTS 38% 46% (SIMVASTATIN EQUIVALENT mAYl 21 29 These changes led a fall in the NYHA class from 2.66f0.79 to 2.37f0.66 Units. CONCLUSIONS: Patients referred to a Heat Failure Clinic are on complex combinations of medications. Despite this. their use of ACE inhbitors. beta-blockers and spironolactone is suboptimal. This type of patient will be increasing in the future Treatment in specialist Heart Failure Clinics may improve outcomes and health care expenditure by more aggressive use of medications shown to prolong survival and reduce hospital readnussions in heart failure
A137
CARDIAC FAILURE IN HOSPITALS: AN AUSTRALIAN REVIEW OF TREATMENT (‘CHART’ PILOT STUDY) A Keoah*. K Smith#. C McCosker. St. Vincent’s Hospital. Sydney, NSW and #Servier, Hawthorn, Vie. To assess the impact of hospitalisation on pharmacotherapy, records of 300 patients with coding ‘heart failure’, admitted to one hospital August 1997-July 1999 were reviewed retrospectively. Patients were 53% male, mean age 70_+14 yrs (vs female 81_+9 yrs) with mean length of stay 9.49.2 days and Class I-II symptoms in 38%, III in 26% and IV in 36%. Coronary angiogram had been performed in 44% and echocardiogram in 48%. Inpatient mortality was 8.7% overall, higher for noncardiology unit than cardiology unit admissions (13.4% vs 4.6%) reflecting older age of non-cardiology unit patient admissrons (80+11 vs 71214 yrs). Inpatient mortality was 5.7% for those on Angiotensin Converting Enzyme Inhibitors (ACEI) at admission vs 11.3% for those not on ACEI at admission. Drua treatment at $lmission Discharge ACEI 57% Carvedilol or metoprolol (BB) 23% 20; Spironolactone 7% 2; A II receptor blockers Aspirin 44% 4::; Warfarin 18% 24% Amiodarone 12% 22% In 93 echo-proven systolic dysfunction patients, 26 (28%) did not taking ACEI at discharge. Of these, 19 had a plausible contraindication (Cl), leaving 7 (8%) undertreated at discharge. Similarly, in 93 systolic dysfunction patients, 69 (74%) were not on discharge BB. Of these, 45 had a potential Cl, leaving 24 (26%) undertreated at discharge. In 90% of ACEI-treated and 91% of BB-treated, doses were low or medium range. Conclusions: Australian females admitted with heart failure coding are on average >I decade older than males. Inpatient mortality is higher in older patients and in those not on ACEI at admission. There is substantial opportunity to add ACEI & BB during inpatient care of heart failure patients. A multicentre national study is underway.
CO-OPERATIVE EXPRESSION OF HEMEOXYGENASE-1 AND NITRlC OXIDE SYNTHASE GENE EXPRESSION IN HUMAN DILATED CARDIOMYOPATHY Walter P-The Queen Elizabeth Hospital, Adelaide; OLV Ziekenhuis, A&, Belgium; Free University Hospital, Amsterdam The intensity of endomyocardial inducible nitric oxide synthase (NOS)Z and constitutive NOS3 expression is closely correlated with lefl ventricular(LV) stroke work in patients with non-ischemic, dilated cardiomyopathy. However, cardio-depressant effects of either high concentrations of NO or of peroxynitrite generation have previously been demonstrated in models involving cytokine induction of NOS acfiv~ty. NO is known to induce increased expression of HO-l mRNA and protein in a variety of situations, such induction being attenuated in the presence of free radical scavengers, consistent with this being a protective cellular mechanism. We have investigated 23 pts with dilated cardiomyopathy by cardiac cathetensation, microtip LV pressure recordmg, angiogmphic LV volume measurement and LV endomyocardial biopsy procurement, for determination of intensity ofNOS2, NOS3 and HO-l expression. Results: Intensity of NOS and HO-l mRNA were both correlated with LV stroke work and negatively correlated with the LV diastolic stiffness modulus (~~0.05 for all). Intensity of endomyocardial HO-l mRNA expression was correlated with both NOS2 (,=0.52, p=O.Ol) and NOS3 (1=0.66, p=O.O007) mRNA. NOS mRNA levels were ranked and added, the result being strongly correlated with HO-1 mRNA expression (I=O.75, p<0.0001) (see figure). Conclusions: High endomyocardial NOS mRNA expression is observed in patients with the least severe clinical phenotype of dilated cardiomyopathy. Co-operative expression of NOS and HO-l may allow for the mediation of the beneficial effects of NO on the diastolic pressure-volume relation of the human left ventricle by protection against the potential adverse effects of peroxynitrite generation. 1004
l
I/ o]$j, , , ( lm
2 2 ‘; P
’
.
50
.
. . . .
0
10
. .
20
30
40
Ranked NOS Score
50
48th Annual Scientific Meeting of CSANZ
2000; 9
OUTCOME IN PATIENTS PARTICIPATING M A PILOT HEART FAILURE CLINIC. S Nicholls*, K Inder, J Lowe, B Bastian, P Candlish, J Holliday and D O’Connell. John Hunter Hospital, Newcastle. Background: Heart failme clinics optimise medical therapy and focus on lifestyle modifications and exercise. The aim of the study was to compare the outcome of patients participating in the clinic with those who refused or were excluded and a cohort of patients admitted with heart failure in 1993. Method: 183 patients were admitted over a 5 month period in 1998 with heart failure. Patients were invited to attend a clinic on discharge involving a home visit, 3 outpatient visits, rehabilitation sessions and an optional exercise pqramme. Clinical data and outcome were recorded. Results: 59 patients participated in the clinic. 50 refused and 74 were excluded. 54% of patients in the clinic group were male and mean age in the clinic group was 71 years (46-98). Patients who refused or were excluded were more likely to be female (64%) and were older with a mean age 79 years (60-95). In comparison to the 1993 cohort, clinic patients were more likely to receive an ACE inhibitor OI angiotensin II blocker (93% v 66%), beta blocker (30% v 6%), diuretics (97% v 71%) and digoxin (63% v 45%). Aspirin (67% v 37%) and warfain (17% v 10%) use was also greater in the clinic group. Clinic patients were less likely to receive calcium antagonists (10% v 24%). 28 day unplanned admission and mortality at 28 days and 12 months are listed in the following table. 1 28DAY 1 28DAY 1 12MON 1 I
~1
Conclusion: An increase in auummiate therapy for patients with heart failure resulted in improved unplan&d r&mission-& l&e change in mortality. Whilst the group who attended the clinic appeared to benefit in terms of reduced mortality and unplanned hospital r&missions, the results may suggest that those patients who are too unwell to take part have a worse outcome.
CHANGES IN TREATMENT AND STATUS OF PATIENTS AFTER ATTENDING A QUATERNARY REFERRAL HEART FAILURE CLINIC. andone*. T Yw MMBwdeich. Heart Failure Unit DepartmntofCanliology. ConcordHospital. Concord NSW. Patients with heart failure are becoming mxe common. complex and unwell requiring frequent homital admissions and multiple medications. Heart failure patients may achieve better out&me iftmna~ed in a Heat F&lure Clinic. We evaluated cha!.&s made to &tmnt of Heart Failure Clinic patients to assess its impact. METHOD: Analysed prior therapy of patients seen in a ouatentm referral Heart Failure Clinic over the past year to determine changu made to managkment. dESULTS: Assessed all 74 patients referred in the part year, aie 68*13 years, 77% male, New York Heart Association (NYHA) class 2.66i0.8 units, 46% ischaemic/54% non-ischaemic heart failure. Left ventricular (LV) ejection fraction was 026iO. 15units, LV end-diastolic diameter64~11 mm LV end-systolic diameter 53fl4 mm and left atria1 diameter 46i8 mm. All calcium channel blocking agents. tricyclic antidepressants and most non-steroidal anti-inflammatory agents were ceased 14% were enrolledinto clinical trials. No medications rose from 5.44kZ.Si to6.77*2.68/day. Changes were: MEDICATION BASELINE FOLLOW-UP ACE INHIBITORS (Angiotcnsin Converting Enzyme) 62% 62% 87 (-EQUMG’DAW 74 DIURETICS 70% 73% 58 @RUS~&UNALEbiTMC&‘DAY) 65 DIGOXIN 32% 34% 113 196 WSE (MO BETA- BLOCKERS 19% 65% (CARVEDlLOL~UIV~MC’DAY) 18 42 SPIRONOLACTONE 15% 43% 30 25 ~.=w3 ANGIOTENSIN ANTAGONISTS 20% 11% (CANDESARTANFQUtV~MCVDAY) 8 11 AMIODARONE 18% 26% 185 137 JJ3.v o”k!) NITRATES 31% 46% (BOSORBIDE MONONI’IRATB EQUNALRNT MG’DAy) 104 85 HYDRALAZINE 7% 8% 63 43 DOSE ms) WARFARIN 24% 24% ASPIRIN 43% 42% 142 131 DOSE MS) CHOLESTEROL LOWERING AGENTS 38% 46% (SIMVASTATIN EQUIVALENT mAYl 21 29 These changes led a fall in the NYHA class from 2.66f0.79 to 2.37f0.66 Units. CONCLUSIONS: Patients referred to a Heat Failure Clinic are on complex combinations of medications. Despite this. their use of ACE inhbitors. beta-blockers and spironolactone is suboptimal. This type of patient will be increasing in the future Treatment in specialist Heart Failure Clinics may improve outcomes and health care expenditure by more aggressive use of medications shown to prolong survival and reduce hospital readnussions in heart failure
A137
CARDIAC FAILURE IN HOSPITALS: AN AUSTRALIAN REVIEW OF TREATMENT (‘CHART’ PILOT STUDY) A Keoah*. K Smith#. C McCosker. St. Vincent’s Hospital. Sydney, NSW and #Servier, Hawthorn, Vie. To assess the impact of hospitalisation on pharmacotherapy, records of 300 patients with coding ‘heart failure’, admitted to one hospital August 1997-July 1999 were reviewed retrospectively. Patients were 53% male, mean age 70_+14 yrs (vs female 81_+9 yrs) with mean length of stay 9.49.2 days and Class I-II symptoms in 38%, III in 26% and IV in 36%. Coronary angiogram had been performed in 44% and echocardiogram in 48%. Inpatient mortality was 8.7% overall, higher for noncardiology unit than cardiology unit admissions (13.4% vs 4.6%) reflecting older age of non-cardiology unit patient admissrons (80+11 vs 71214 yrs). Inpatient mortality was 5.7% for those on Angiotensin Converting Enzyme Inhibitors (ACEI) at admission vs 11.3% for those not on ACEI at admission. Drua treatment at $lmission Discharge ACEI 57% Carvedilol or metoprolol (BB) 23% 20; Spironolactone 7% 2; A II receptor blockers Aspirin 44% 4::; Warfarin 18% 24% Amiodarone 12% 22% In 93 echo-proven systolic dysfunction patients, 26 (28%) did not taking ACEI at discharge. Of these, 19 had a plausible contraindication (Cl), leaving 7 (8%) undertreated at discharge. Similarly, in 93 systolic dysfunction patients, 69 (74%) were not on discharge BB. Of these, 45 had a potential Cl, leaving 24 (26%) undertreated at discharge. In 90% of ACEI-treated and 91% of BB-treated, doses were low or medium range. Conclusions: Australian females admitted with heart failure coding are on average >I decade older than males. Inpatient mortality is higher in older patients and in those not on ACEI at admission. There is substantial opportunity to add ACEI & BB during inpatient care of heart failure patients. A multicentre national study is underway.
CO-OPERATIVE EXPRESSION OF HEMEOXYGENASE-1 AND NITRlC OXIDE SYNTHASE GENE EXPRESSION IN HUMAN DILATED CARDIOMYOPATHY Walter P-The Queen Elizabeth Hospital, Adelaide; OLV Ziekenhuis, A&, Belgium; Free University Hospital, Amsterdam The intensity of endomyocardial inducible nitric oxide synthase (NOS)Z and constitutive NOS3 expression is closely correlated with lefl ventricular(LV) stroke work in patients with non-ischemic, dilated cardiomyopathy. However, cardio-depressant effects of either high concentrations of NO or of peroxynitrite generation have previously been demonstrated in models involving cytokine induction of NOS acfiv~ty. NO is known to induce increased expression of HO-l mRNA and protein in a variety of situations, such induction being attenuated in the presence of free radical scavengers, consistent with this being a protective cellular mechanism. We have investigated 23 pts with dilated cardiomyopathy by cardiac cathetensation, microtip LV pressure recordmg, angiogmphic LV volume measurement and LV endomyocardial biopsy procurement, for determination of intensity ofNOS2, NOS3 and HO-l expression. Results: Intensity of NOS and HO-l mRNA were both correlated with LV stroke work and negatively correlated with the LV diastolic stiffness modulus (~~0.05 for all). Intensity of endomyocardial HO-l mRNA expression was correlated with both NOS2 (,=0.52, p=O.Ol) and NOS3 (1=0.66, p=O.O007) mRNA. NOS mRNA levels were ranked and added, the result being strongly correlated with HO-1 mRNA expression (I=O.75, p<0.0001) (see figure). Conclusions: High endomyocardial NOS mRNA expression is observed in patients with the least severe clinical phenotype of dilated cardiomyopathy. Co-operative expression of NOS and HO-l may allow for the mediation of the beneficial effects of NO on the diastolic pressure-volume relation of the human left ventricle by protection against the potential adverse effects of peroxynitrite generation. 1004
l
I/ o]$j, , , ( lm
2 2 ‘; P
’
.
50
.
. . . .
0
10
. .
20
30
40
Ranked NOS Score
50