S1-03 Investigation medical therapy in heart failure

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Abstracts/International Journal of Cardiology 97 SuppL 2 (2004) S1~75

to mortality from ischemic heart disease, cerebrovascular diseases and hypertensive diseases. Rheumatic fever and RHDs constituted 2.3% of CVD deaths in 1998. Comprehensive data on risk factors and cardiovascular diseases in the Philippines are still lacking. A nationwide survey on hypertension in 1997 to 98 revealed a prevalence of 22%. This prevalence is a considerable increase from the 11% in 1992. Ooly 13% were aware of their hypertension, 37% were being treated, 44% were complaint and 43% have their high blood plessures controlled. Target organ damage was seen in 59%. The heart was affected in 45%, kidneys in 17% and bialn in 18%. LVH was the most coiimlon finding (32%) followed by IHD (24%). In 2001, Tiglao et al showed a prevalence of 23.5% current smokers among 15 to 74 years old and 11.1% frequent alcohol di~nkers. However, 79.3% among those surveyed do regular exercises. Baltazar et al in 2002 showed that hypertension among 20 65 years old in the National Capital Region, urban and rural Luzon ranged from 18.4 to 21.8%, diabetes from 4.78 to 5.3% and impaired glucose from 7.9 to 10.90%. Filipinos generally have low total cholesterol and also low HDL.

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Pharmacologic Therapy of Heart Failure $1-01 CARDIAC REMODELLING: AN IMPORTANT TREATMENT T A R G E T IN H E A R T F A I L U R E

Norman Sharpe. University of Auckland, New Zealand Cardiac remodelling has been redefined as genome expression resulting in molecular, cellular and interstitial changes manifested clinically as changes in size, shape and function of the heart resulting from cardiac load or inj m3J. Cardiac remodelling in the context of hypertensive heart disease (ven tflcular hypertrophy and diastolic dysfunction) and following myocardial infarction (ventricular dilatation and systolic dysfunction) is an adverse, progressive process, which confers a poor prognosis. Treatment alms for patients with hypertension, following myocardial infarction and with con gestive heart failure should take consideration of underlying mechanisms and be bioadened to include cardiac remodelling as a target for therapy. Cardiac remodelling is influenced by haemodynamic load and neurohor monal activation. Furthermore, cardiac remodelling is closely related to long term outcomes for which it is a reliable surrogate. More vigorous anti hypertensive treatment should be aimed at achieving tree normalization of blood pressure and regressing ventricular hypeI~ro phy. Patients with ventricular systolic dysfunction following myocardial infarction should receive ACE inhibitor treatment to prevent progi~ssive ventricular dilatation and dysfunction and improve long term outcomes with betablocker treatment added once this is established. Similarly, in congestive heart failure, combination neurohormonal blockade with ACE inhibitor and betablocker treatment provides additive benefits in improving ventricular remodelling and survival. In surfing-y, there is concordance between changes in cardiac remod elling and survival. Improved long term outcomes in cardiac patients may depend on neurohormonal blockade and i~versal of remodelling which can be effectively targeted with modern treatment.

$1-02 T H E R O L E O F A R B IN T H E T R E A T M E N T OF H E A R T F A I L U R E Chung Sheng Lin. Chung Shah Medical University Hospital, Taichung,

Taiwan Angiotensin converting enzyme inhibitor (ACEI) has become the corner stone of therapy in heart failure (HF). However, the mortality of HF remain

high. Specific Angiotensin II(Ag II) receptor blocker (ARB) provide more complete blockade of Ag II than ACEI alone, Evidence from early clinical studies support the use of ARBs in HE The Evaluation Of Losartan In The Elderly (ELITE II) tflal studied 3152 elderly patients and did not find a survival advantage for losartan over captopril. Valsaltan Heart Failure Trial (Val HEFT), a total of 5010 patients with symptomatic HF (class II IV) were randomized to valsartan or placebo, Mortality was similar in the two treatment groups. However, combined end point of mortality and morbidity was lower with valsartan compared to placebo (p 0.009). Subgroup analysis according to background therapy at baseline (ACEI and/or beta blocker) shown valsartan had a favorable effect in patients ~eceiving neither or one of these types of drugs, but a significant adverse effect on mortality in patients ieceiving both therapies, The Candersartan In Heart Failure~ssessment Of Reduction In Mot tality And Morbidity (CHARM) study consists of three independent parallel placebo controlled studied in patients with class II IV HF, (1) CHARM Alternative enrolled left ventdcular ejection fraction (LVEF) < 40% patients who were ACEI intolerant (n 2028) (2) CHARM Added evaluated LVEF < 40% patients already on optimal ACEI (55% were on beta blocker too) (n 2548) (3) CHARM Pi~served enrolled patients LVEF < 40% and no treated with ACEI (n 3025). The study results of CHARN Alternative shown candesartan alone significantly reduced each individual component of the composite primary endpoint. In the CHARM Added study, the addition of candesartan to ACEI and other therapy led to further clinical important reduction in cardiovascular events. Candesartan had a moderate impact in preventing a&nission for HF among patients with LVEF>40% in CHARM Reserved, Summary, the ARB alone is proved beneficial in U~aUnent of HE Combination therapy of ARB and ACEI offers beneficial effect, The triple combination therapy (ARB + ACEI + beta blocker) need further confirmation.

$1-03 INVESTIGATION MEDICAL THERAPY IN HEART FAILURE Min~ Jal Su, Wei Luen Chang, An Sheng Lee. Institute of Pharmacolog~

College of Medicine, National Taiwan University, Tuipei, Taiwan I n t r o d u c t i o n : Ischemic heart disease accounts for 50% of all cardiovas cular deaths and is the leading cause of congestive heart failure. Therefore, search for agents to prevent cardiac injury and to preserve the remaining myocardial function become a major medical challenge for the research scientists. The aim of this study was to evaluate the efficacy of L S N T U 106 (achllinistrated at the ~ n e of coronary perfusion) to prevent ischemia reperfusion injury. On the other hand, we planned to examine the safety and efficacy of a cardiac glycoside AT 11 to increase cardiac contlactility of guinea pig. Methods: Anesthetized, open chest rats subjected to 60 rain coronary occlusion and 120 rain reperfusion were used to assess cardioprotective efficacy of LS NTU 106. A microtip pressui~ transducer was induced into the left ventricle to measure contractile function. Results: hlfarct size was reduced by LS NTU 106 dose dependently (107 to 10 6 mole kg 1). Plasma creatine ldnase and cardiac myoloperox idase (MPO) activities were also reduced. Recovery of developed LVR rate of pressure development (+dP/dt) and relaxation (dP/dt) were all significantly improved in rats ti~ated with LS NTU 106. These protective effects were abrogated by naloxone and mitochondi~al KATp channels blocker 5HD. In expeliment of AT 11, we found it increased force of contraction in left atria and papillary muscle, enhanced LVP in guinea pigs. It showed less alThythmogenic activity and better inotropic efficacy than ouabaln. C o n c l u s i o n : L S N T U 106 can prevent I/R injui3J via activation of opioid ieceptors and opening/nitochondlial KATp channels, AT 11 exerts inotropic action with Nmilar mechanism but better efficacy and safety than ouabaln,