Change in Systolic Left Ventricular Performance After 3 Years of Antihypertensive Treatment

Wachtell, Kristian; Palmieri, Vittorio; Olsen, Michael Hecht; Gerdts, Eva; Papademetriou, Vasilios; Nieminen, Markku S.; Smith, Geoffrey; Dahlöf, Björn; Aurigemma, Gerard P.; Devereux, Richard B.

doi:10.1161/01.cir.0000021601.49664.2a

Cited by 73 publications

(30 citation statements)

References 44 publications

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“…Moreover, this mechanism may be activated more strongly if cardiac Ang II is activated in the heart. AT1 receptor blockers have been reported to improve the cardiac structure and function by way of reducing the hemodynamic load [9,22], but no improvement was observed in the present study. A possible reason for this result was considered to be that the Bio TO2 hamsters revealed an inherited pathophysiological change, such as a decrease in wall thickness due to enlargement of the heart chamber, during the 4 weeks and the AT1 receptor blocker could not improve the inherited changes.…”

Section: Discussioncontrasting

confidence: 82%

Effect of Angiotensin II Type 1 Receptor Blocker on Cardiac Angiotensin-Converting Enzyme and Chymase-Like Activities, and Cardiac Fibrosis in Cardiomyopathic Hamsters

Shimizu

Tanaka

Uchida

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. It has been reported that cardiac chymase has an effect on cardiac fibrosis through the Angiotensin (Ang) II formation and an Ang II-independent mechanism. In the present study, Ang II type 1 (AT1) receptor blocker (candesartan cilexetil) was administered to dilated cardiomyopathic (DCM; Bio TO2) hamsters for 4 weeks to study the effect of AT1 receptor blocker on cardiac chymase-like activity and cardiac fibrosis. Echocardiography, histological examination, and assessment of cardiac angiotensin-converting enzyme (ACE)/chymase-like activities were conducted. Hamsters showed cardiac dysfunction due to increased left ventricular dimensions and decreased ventricular wall thickness, significant increase in cardiac chymase-like activity, and fibrosis. This result indicates that the cardiac chymase-like activity is responsible for cardiac fibrosis. When candesartan cilexetil was administered to Bio TO2 hamsters, cardiac chymase-like activity increased significantly, whereas cardiac fibrosis decreased significantly. Cardiac ACE and chymase-like activities were unchanged in non-DCM hamsters with candesartan cilexetil. This suggests that the cardiac Ang II formation mechanism was stimulated by suppressing the effect of cardiac Ang II, and cardiac chymase-like activity could be increased. Moreover, this mechanism may be more highly activated if cardiac Ang II is activated in the heart. In conclusion, we demonstrated that AT1 receptor blocker reduced cardiac fibrosis, although cardiac chymase-like activity increased. Because the Ang II-forming pathway and the effect of chymase in hamsters is similar to that in dogs, the results of the present study may supplement the available information for dogs. KEY WORDS: angiotensin-converting enzyme, chymase, heart failure, remodeling, renin-angiotensin system. J. Vet. Med. Sci. 68(3): 227-233, 2006 The renin-angiotensin system (RAS) is an adaptive mechanism of the body that maintains circulatory homeostasis and cardiac function in the presence of excessive hemodynamic overload. Although it has been thought that RAS exists only in the circulatory system (circulating RAS), RAS also has been found to exist in the heart (cardiac RAS) [14,24]. Angiotensin (Ang) II, one of the effector peptides of RAS, is known as a causative agent of cardiac remodeling [15]. The Ang II-forming mechanism in the dog's heart is the same as that in humans. In both dogs and humans, cardiac Ang II is produced not only by the cardiac angiotensinconverting enzyme (ACE)-dependent pathway, but also by the cardiac chymase-dependent pathway [1,2,23]. The presence of this alternative pathway indicates that ACE inhibitors cannot completely inhibit the cardiac Ang II. A study in rats revealed that Ang II type 1 (AT1) receptor blockers reduced the hemodynamic load and cardiac remodeling by inhibiting the effect of Ang II at the receptor level, and consequently improved cardiac function [20]. Due to this difference in the effector site, AT1 receptor blockers are expected to be more superior to ACE inhibitors....

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Section: Discussioncontrasting

confidence: 82%

Effect of Angiotensin II Type 1 Receptor Blocker on Cardiac Angiotensin-Converting Enzyme and Chymase-Like Activities, and Cardiac Fibrosis in Cardiomyopathic Hamsters

Shimizu

Tanaka

Uchida

et al. 2006

The Journal of Veterinary Medical Science

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“…In addition, LVH regression has been reported to improve LV systolic performance 30 . A total of 679 hypertensive patients with electrocardiogram (ECG) evidence of LVH from the LIFE sub-study were followed with a yearly echocardiogram during 3 years of antihypertensive treatment.…”

Section: Clinical Applicabilitymentioning

confidence: 99%

Regression of left ventricular hypertrophy: Lessons from clinical trials

Pokharel¹,

Jn²

2013

OA Evidence-Based Medicine

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IntroductionHypertension is an epidemic that affects more than 1 billion people worldwide annually. Left ventricular hypertrophy is the phenotypic expression of hypertensive heart disease, which depends on complex interactions among genetic makeup, environmental factors and lifestyle. Left ventricular hypertrophy has been shown to be independently associated with adverse cardiovascular morbidity and mortality. Targeting left ventricular hypertrophy with different pharmacological agents and lifestyle modifications has been associated with favourable results and results in improved outcome. Evidence shows that the drug targets renninangiotensin-aldosterone are more effective system in reducing left ventricular mass. Moving forward, the new frontier in this field will be to understand the genetic influences on left ventricular hypertrophy regression and progression and ways to intervene early and treat this public health burden. ConclusionTargeting left ventricular hypertrophy regression with various antihypertensive agents results in improved clinical outcomes. Therefore regression of LVH can be considered surrogate endpoint in the treatment of hypertensive heart disease

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“…16 Inverse LVM inappr ϪLV systolic chamber function relations 18-24 may, therefore, reflect compensatory increases in LVM as a consequence of systolic dysfunction or associated confounding effects. Although one previous study has reported that on-treatment regression but not persistence of LVM inappr is associated with an improved EF, 25 whether…”

Section: Abstract-althoughmentioning

confidence: 99%

“…Moreover, LVH may even be associated with an enhanced EF for that predicted by wall stress, 15 and on-treatment decreases in LVM have been related to reductions rather than increases in indices of systolic LV chamber function. 16 There is, therefore, considerable uncertainty as to whether LVH contributes to decreases in systolic chamber function.One possibility that may explain discrepancies in the ability to show consistent relations between LVM or LVM index (LVMI) and a reduced systolic LV chamber function [11][12][13][14][15][16] is that absolute LVM and LVMI may incorporate a component of LVH considered compensatory in nature, whereas there may also be a component of LVH that contributes to decompensation. In this regard, LVM in excess of that predicted by workload (ie, stroke workϭblood pressure [BP]ϫstroke volume), termed "inappropriate LVM" (LVM inappr ), 17 is inversely associated with systolic LV chamber function.…”

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confidence: 99%

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Relationship Between On-Treatment Decreases in Inappropriate Versus Absolute or Indexed Left Ventricular Mass and Increases in Ejection Fraction in Hypertension

Woodiwiss

Libhaber

et al. 2012

Hypertension

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Abstract-Although) LVMI decreased with treatment, treatment failed to increase EF in either group (1.2Ϯ10.8% and 2.7Ϯ10.7%, respectively). In contrast, in patients with inappropriate LV hypertrophy (LVM inappr Ͼ150%; nϭ33) LVM inappr decreased (Ϫ32Ϯ27%; PϽ0.0001) and EF increased (5.0Ϯ10.3%; PϽ0.05) after treatment, whereas in patients with an LVM inappr Յ150% (nϭ135), neither LVM inappr (Ϫ0.5Ϯ23%) nor EF (0.9Ϯ10.3%) changed with therapy. With adjustments for circumferential LV wall stress and other confounders, whereas on-treatment decreases in LVM or LVMI were weakly related to an attenuated EF (partial rϭ0.17; PϽ0.05), on-treatment decreases in LVM inappr were strongly related to increases in EF even after further adjustments for LVM or LVMI (partial rϭϪ0.63 [CI, Ϫ0.71 to Ϫ0.52]; PϽ0.0001). In conclusion, decreases in LVM inappr are strongly related to on-treatment increases in EF beyond changes in LVM and LVMI. LV hypertrophy can, therefore, be viewed as a compensatory change that preserves EF, but when in excess of that predicted by stroke work, it can be viewed as a pathophysiological process accounting for a reduced EF. 1-7 and the development of a reduced ejection fraction (EF) 8 independent of myocardial infarction. LV mass (LVM) may, therefore, determine the progression to heart failure with a reduced rather than a preserved EF. 9,10 However, in keeping with the classic tenet that LVH is a compensatory response to LV load, an increased LVM 11-13 or on-treatment decreases in LVM 14 have been associated with an unchanged EF. Moreover, LVH may even be associated with an enhanced EF for that predicted by wall stress, 15 and on-treatment decreases in LVM have been related to reductions rather than increases in indices of systolic LV chamber function. 16 There is, therefore, considerable uncertainty as to whether LVH contributes to decreases in systolic chamber function.One possibility that may explain discrepancies in the ability to show consistent relations between LVM or LVM index (LVMI) and a reduced systolic LV chamber function [11][12][13][14][15][16] is that absolute LVM and LVMI may incorporate a component of LVH considered compensatory in nature, whereas there may also be a component of LVH that contributes to decompensation. In this regard, LVM in excess of that predicted by workload (ie, stroke workϭblood pressure [BP]ϫstroke volume), termed "inappropriate LVM" (LVM inappr ), 17 is inversely associated with systolic LV chamber function.18-25 However, these relationships have largely been demonstrated in cross-sectional studies [18][19][20][21][22][23][24] and are at odds with on-treatment decreases in systolic LV chamber function associated with LVH regression. 16 Inverse LVM inappr ϪLV systolic chamber function relations 18-24 may, therefore, reflect compensatory increases in LVM as a consequence of systolic dysfunction or associated confounding effects. Although one previous study has reported that on-treatment regression but not persistence of LVM inappr is associated with an improved EF, 25 wh...

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Change in Systolic Left Ventricular Performance After 3 Years of Antihypertensive Treatment

Cited by 73 publications

References 44 publications

Effect of Angiotensin II Type 1 Receptor Blocker on Cardiac Angiotensin-Converting Enzyme and Chymase-Like Activities, and Cardiac Fibrosis in Cardiomyopathic Hamsters

Effect of Angiotensin II Type 1 Receptor Blocker on Cardiac Angiotensin-Converting Enzyme and Chymase-Like Activities, and Cardiac Fibrosis in Cardiomyopathic Hamsters

Regression of left ventricular hypertrophy: Lessons from clinical trials

Relationship Between On-Treatment Decreases in Inappropriate Versus Absolute or Indexed Left Ventricular Mass and Increases in Ejection Fraction in Hypertension

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