Reduction Of Left Ventricular Hypertrophy Research Articles

Hypertension, left ventricular hypertrophy and chronic kidney disease

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.

Prevalence and Predictive Factors of Anemia after Renal Transplantation: A Moroccan Report

Objective Anemia, a common multifactorial problem in kidney transplant recipients, represents an important cardiovascular risk factor. The purpose of this study was to assess anemia prevalence after kidney transplantation, the main factors involved in its occurence, its cardiovascular consequences, and its impact on patient survival and graft function. Methods This retrospective study evaluated 69 patients undergoing renal transplantation between January 1998 and September 2008 with ≥1 year of follow-up. For all of the patients, we recorded hemoglobin concentrations before and at 1, 3, 6, 12, 36, and 60 months after transplantation. Anemia was defined as recommended by the American Society of Transplantation: hemoglobin level <12 g/dL in women and <13 g/dL in men. To determine the factors involved in anemia occurrence, we compared 2 groups of patients, with versus without anemia, at various times after renal transplantation. Results This study showed a high prevalence of anemia in the early posttransplantation period of 82.7% and 42% of kidney transplantation patients at 1 month and 6 months, respectively. It was mainly related to a low pretransplant hemoglobin level. The prevalence declined to 37.7% at 1 year. Renal graft dysfunction was the most important factor in the occurrence of late post–renal transplantation anemia. The presence of anemia increased the risk of renal graft functional deterioration by a factor of 2.9. The decreased prevalence at 1 year after transplantation was significantly associated with a reduction in left ventricular hypertrophy. Conclusion The management of anemia is essential to improve renal graft survival, reduce cardiovascular morbidity, and ensure a better quality of life for renal transplant recipients.

Biventricular pacing in hypertrophic obstructive cardiomyopathy: A pilot study

Right ventricular apex pacing for gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM) with severe left ventricular (LV) obstruction has yielded conflicting results. The purpose of this study was to assess the feasibility and effectiveness of biventricular pacing in HOCM. Transvenous biventricular pacing was attempted in 12 severely symptomatic HOCM patients. Optimal intervals were programmed after implant. Echocardiographic LV pressure gradient and synchrony were assessed. LV lead implantation was successful in 9 patients. Optimal pacing mode was biventricular in 6 patients, left ventricular only in 2 patients, and right ventricular only in 1 patient. Functional capacity and quality of life progressively improved. New York Heart Association functional class decreased from 3.2 ± 0.4 at baseline to 1.9 ± 0.3 at 3 months and to 1.4 ± 0.5 at 1 year (P <.05); 6-minute walk test increased from 349 ± 116 m at baseline to 454 ± 144 m at 3 months and to 517 ± 206 m (P <.05); and quality of life increased from 54 ± 16 points at baseline to 28 ± 13 points at 3 months and 27 ± 15 points at 1 year (P <.05). There was also a progressive reduction in LV gradient from 74 ± 23 mmHg at baseline to 50 ± 27 mmHg acutely, 40 ± 26 mmHg at 3 months, and 28 ± 17 mmHg at 1 year (P <.05). Gradient reduction was associated with diminished peak longitudinal displacement of the LV septum and earlier displacement of the lateral wall. A progressive reduction of LV mass was observed, from 356 ± 110 g at baseline to 315 ± 70 g at 3 months (P = .13) and to 284 ± 42 g at 1 year (P <.05). Biventricular pacing is feasible and usually the best configuration for gradient reduction in HOCM. Biventricular pacing reduces LV hypertrophy.

Cardiovascular Risk-Benefit Profile of Sibutramine

Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of these complex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular outcomes might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT (Sibutramine Cardiovascular and Diabetes Outcome Study) was designed to prospectively evaluate the efficacy/safety ratio of sibutramine in a high-risk population. The efficacy/safety results of the first 6-week lead-in open period of treatment with sibutramine 10 mg/day were reassuring in 10 742 overweight/obese high-risk subjects (97% had cardiovascular disease, 88% had hypertension, and 84% had type 2 diabetes mellitus). However, the final results of SCOUT showed that long-term (5 years') treatment with sibutramine (10-15 mg/day) exposed subjects with pre-existing cardiovascular disease to a significantly increased risk for nonfatal myocardial infarction and nonfatal stroke, but not cardiovascular death or all-cause mortality. Because the benefit of sibutramine as a weight-loss aid seems not to outweigh the cardiovascular risks, the European Medicines Agency recommended the suspension of marketing authorizations for sibutramine across the EU. The US FDA stated that the drug should carry a 'black box' warning due to an increased risk of stroke and heart attack in patients with a history of cardiovascular disease. In conclusion, concern still persists about the safety profile of sibutramine regarding cardiovascular outcomes, and the drug should not be prescribed for overweight/obese patients with a high cardiovascular risk profile.

REVERSE CARDIAC REMODELING IN DIALYSIS: THE IMPACT ON OUTCOMES: PP.22.360

Introduction: Left ventricular hypertrophy (LVH) is common in hemodialysis patients (HD) and predicts cardiovascular outcome. Although the reversal is potentially beneficial, such issues in dialysis patients are poorest studied. The aim of this study is to evaluate, in HD patients, the influence of LVH regression on mortality and if the improvement of the risk factors involved in LVH may induce reverse remodeling. Methods: Single center, observational and longitudinal study that included consecutive HD patients, evaluated from June 2000 to October 2006, follow-up to June 2009, whose clinical, laboratory and two consecutive echocardiograms (ECO) were available. Results: From 132 patients, 54 were excluded, 46 w/o two ECO evaluations and 9 met some exclusion criteria, leaving 77 eligible patients. The median interval between assessments was 13 mo, median and maximal follow-up after the second assessment was 28 and 89 mo respectively. Mean age was 54 ± 13.8 years, 33 women, 20 blacks and 2 Asians. LVH reduction was observed in 40 patients and in 37 there was worsening. There were 10 deaths among patients that failed to reverse LVH and 6 among those that reverted. There were 9 deaths from cardiovascular causes among non-reversed LVH and two between those that reversed. Cox regression revealed that reversal of LVH was associated with lower mortality - RR 0.35 (95% CI: 0.121 – 1.016) p = 0.048 (corrected for age and calcium-phosphorus product) and lower cardiovascular mortality - RR 0.188 (95 %: 0.041–0.874) p = 0.014. Logistic regression revealed that reversal of hypertrophy was associated with angiotensin-converting enzyme (ACE) inhibition treatment (RR: 4.51; 95% CI: 1.423–14.291, p = 0.007) and control of parathyroid hormone (RR 0.998 95% 0.997 - 0.999) p = 0.025. In conclusion, this study demonstrates that LVH regression is possible in HD patients if ACE inhibition treatment and control of hyperparathyroidism. This regression was associated with a better cardiovascular outcome driving our efforts to the task of control LVH to improve survival in such patients.

Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction

The study examined the long-term outcome of cardiac stem cell transplantation in hearts with postinfarction left ventricular (LV) remodeling. Myocardial infarction (MI) was created by ligating the first and second diagonal branches of the left anterior descending coronary artery in miniature swine. Intramyocardial injections of 50 million LacZ-labeled bone marrow-derived multipotent progenitor cells (MPC) were performed in the periscar region (Cell, n = 7) immediately after MI, whereas, in control animals (Cont, n = 7), saline was injected. Functional outcome was assessed monthly for 4 mo with MRI and (31)P-magnetic resonance spectroscopy. Engraftment was studied on histology, and gene chip (Affymetrix) array analysis was used to study differential expression of genes in the two groups. MPC treatment resulted in improvement of ejection fraction as early as 10 days after MI (Cell, 43.4 +/- 5.1% vs. Cont, 32.2 +/- 5.5%; P < 0.05). This improvement was seen each month and persisted to 4 mo (Cell, 51.2 +/- 4.8% vs. Cont, 35.7 +/- 5.0%; P < 0.05). PCr-to-ATP ratio (PCr/ATP) improved with MPC transplantation, which was most pronounced at high cardiac work states (subendocardial PCr/ATP was 1.70 +/- 0.10 vs. 1.34 +/- 0.14, P < 0.05). There was no significant difference in scar size (scar/LV area * 100) at 10 days postinfarction. However, at 4 mo, there was a significant decrease in scar size in the Cell group (Cell, 4.6 +/- 1.0% vs. Cont, 8.6 +/- 2.4%; P < 0.05). No significant engraftment of MPC was observed. MPC transplantation was associated with a downregulation of mitochondrial oxidative enzymes and increased levels of myocyte enhancer factor 2a and zinc finger protein 91. In conclusion, MPC transplantation leads to long-term functional and bioenergetic improvement in a porcine model of postinfarction LV remodeling, despite no significant engraftment of stem cells in the heart. MPC transplantation reduces regional wall stresses and infarct size and mitigates the adverse effects of LV remodeling, as seen by a reduction in LV hypertrophy and LV dilatation, and is associated with differential expression of genes relating to metabolism and apoptosis.

ANGIOTENSIN II RECEPTOR ANTAGONISTS AND ACE INHIBITORS: OPTIMIZATION OF CHOICE FOR TREATMENT OF CARDIOVASCULAR DISEASES

Aim. To evaluate the cardioprotective effects of ACE inhibitor, ramipril and angiotensin II receptor antagonist (ARA), valsartan at the cardiovascular continuum (CVC) stages. Material and methods. 577 patients were examined. Patients with arterial hypertension (HT) (n=283; group 1), with metabolic syndrome (n=137; group 2), with HT associated with ischemic heart disease (n=157; group 3) were randomized into treatment subgroups A (ramipril) and B (valsartan). All patients had clinical examination, transthoracic echocardiography with remodeling indexes calculation, ambulatory blood pressure monitoring initially and after 6 months of therapy. Results. Valsartan had priority in prevention of early cardiac remodeling (reduction in left ventricular (LV) hypertrophy and myocardial stress, improvement of functional heart parameters) at early CVC stage (HT, metabolic syndrome). On the other hand ramipril had priority at advanced stage of CVC (reduction in systolic diameter-thickness ratio, LV hypertrophy, myocardial stress and myocardial stiffness). At the advance stage of CVC valsartan treatment also resulted in significant reduction in LV hypertrophy and myocardial stress, improvement in cardiac remodeling functional parameters but had no effect on LV diameter-thickness ratio. Conclusion. The ARA treatment is preferred at early CVC stage for better cardioprotection.

Hypertensive Heart Disease – Diagnosis, Prognostic Value and Changes During Antihypertensive Treatment, Left Ventricular Structure and Function

Hypertensive heart disease is prevalent and during the last decade it has been determined that patients with left ventricular (LV) hypertrophy have increased cardiovascular morbidity and mortality. However, many have doubted the effectiveness of LV mass assessment because it is difficult to measure, and there were no data showing a relation between reduced LV mass and improvement in LV systolic and diastolic function and improved cardiovascular outcome. However, improvements to echocardiographic equipment have made it possible to measure LV mass with the same precision as for aortic valve replacement. Reduction of LV hypertrophy, independent of the simultaneous blood pressure reduction, is associated with large improvements in cardiovascular morbidity and mortality. A reduction in LV mass by 25g/m² leads to a 34% reduction in cardiovascular mortality. Time-varying analyses showed 66% associated risk reduction in cardiovascular mortality if patients with LV hypertrophy were treated to limits of LV mass. Hypertension causes impaired LV systolic function by increased afterload and LV hypertrophy. Normal estimations of LV ejection fraction tend to overestimate LV systolic function; however, improvement of LV systolic function by antihypertensive treatment leads to an improvement of cardiovascular morbidity and mortality. Furthermore, even though there is significant improvement in LV diastolic function during antihypertensive treatment, this occurs more slowly compared with the treatment effects on LV systolic function, and diastolic function does not, compared with LV systolic function, translate into improvement in cardiovascular morbidity and mortality. The perspective of finding cardiac target organ damage is used not only to classify the cardiovascular risk of patients, but also to indicate to the treating physician that specific treatment is needed.

New Approaches to Pathogenesis and Management of Hypertension

New Approaches to Pathogenesis and Management of Hypertension

Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study

Background and aims Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb). Methods and results We studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage–duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb ( p < 0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p < 0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb. Conclusions Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.

Die I-PRESERVE-Studie: Sartane und ACE-Hemmer bei diastolischer Herzinsuffizienz

The renin-angiotensin-aldosteron-system (RAAS) appears to play a key role not only in the pathophysiology of systolic but also of „diastolic” heart failure. In the prospective, randomized, double-blind I-PRESERVE study irbesartan (target dose 300 mg/day) did not improve mortality and morbidity in patients (n = 4128) with heart failure and preserved left ventricular ejection fraction (LVEF). In contrast to systolic heart failure, patients with „diastolic” heart failure obviously do not benefit prognostically from treatment with a sartan. Besides early and intense blood pressure control therapy of „diastolic” heart failure remains to be based on empiric approaches including (I) reduction of cardiac filling pressures with diuretics, (II) improvement of ventricular filling by rate control with beta-blockers, (III) reduction of leftventricular hypertrophy by ACE inhibitors or sartans, and (IV) reduction of myocardial stiffness (e. g. fibrosis) with aldosterone antagonists.

Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy

Enzyme replacement therapy with recombinant alpha-galactosidase A reduces left ventricular hypertrophy and improves regional myocardial function in patients with Fabry disease during short-term treatment. Whether enzyme replacement therapy is effective in all stages of Fabry cardiomyopathy during long-term follow-up is unknown. We studied 32 Fabry patients over a period of 3 years regarding disease progression and clinical outcome under enzyme replacement therapy. Regional myocardial fibrosis was assessed by magnetic resonance imaging late-enhancement technique. Echocardiographic myocardial mass was calculated with the Devereux formula, and myocardial function was quantified by ultrasonic strain-rate imaging. In addition, exercise capacity was measured by bicycle stress test. All measurements were repeated at yearly intervals. At baseline, 9 patients demonstrated at least 2 fibrotic left ventricular segments (severe myocardial fibrosis), 11 had 1 left ventricular segment affected (mild fibrosis), and 12 were without fibrosis. In patients without fibrosis, enzyme replacement therapy resulted in a significant reduction in left ventricular mass (238+/-42 g at baseline, 202+/-46 g at 3 years; P for trend <0.001), an improvement in myocardial function (systolic radial strain rate, 2.3+/-0.4 and 2.9+/-0.6 seconds(-1), respectively; P for trend=0.045), and a higher exercise capacity obtained by bicycle stress exercise (106+/-14 and 122+/-26 W, respectively; P for trend=0.014). In contrast, patients with mild or severe fibrosis showed a minor reduction in left ventricular hypertrophy and no improvement in myocardial function or exercise capacity. These data suggest that treatment of Fabry cardiomyopathy with recombinant alpha-galactosidase A should best be started before myocardial fibrosis has developed to achieve long-term improvement in myocardial morphology and function and exercise capacity.

ROLE OF CARDIAC HYPERTROPHY IN REDUCING THE SENSITIVITY OF CARDIOPULMONARY REFLEX CONTROL OF RENAL SYMPATHETIC NERVE ACTVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

The gain of the volume-sensitive cardiopulmonary reflex (VSCR) is impaired in spontaneously hypertensive rats (SHR). Sensitivity of VSCR control of efferent renal sympathetic nerve activity (RSNA) in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. The present study investigated which of these two parameters, cardiac hypertrophy or hypertension, has more influence on the impairment of VSCR control of RSNA in SHR. Rats (SHR or Wistar-Kyoto (WKY) rats) were treated with enalapril (10 mg/kg per day; SHRE and WKYE groups, respectively) or hydralazine (5 mg/kg per day; SHRH and WKYH groups, respectively) mixed in their food for 1 month. Control SHR and WKY rats were fed a normal diet. After the treatment regimen, the VSCR was evaluated by determining the decrease in RSNA elicited by acute isotonic saline volume expansion. Mean arterial pressure (MAP) was assessed via an intrafemural catheter and cardiac hypertrophy was determined by the left ventricular (LV) weight/bodyweight (BW) ratio. Afferent baroceptor nerve activity (BNA) was also evaluated during volume expansion to verify participation of the baroreflex. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR compared with WKY rats. Enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE (-41 +/- 8%) compared with WKY rats (-44 +/- 3%). Although both enalapril and hydralazine treatment reduced MAP in SHR (P < 0.01; 126 +/- 5, 133 +/- 6 and 160 +/- 6 mmHg in SHRE, SHRH and SHR, respectively), hydralazine did not restore the sensitivity of VSCR control of RSNA in SHRH. Spontaneously hypertensive rats with established hypertension had a higher LV/BW ratio compared with WKY rats (3.22 +/- 0.14 vs 1.98 +/- 0.06 mg/g, respectively; P < 0.01). Enalapril reduced the LV/BW ratio in SHRE (2.30 +/- 0.07 mg/g; P < 0.01). Although hydralazine reduced LV hypertrophy, there was a weaker reduction in SHRH (2.68 +/- 0.04 mg/g; P < 0.05) compared with SHRE. There was no statistically significant difference among the WKY rat, WKYE and WKYH groups (P > 0.05). There was no change in afferent BNA during volume expansion in normal or hypertensive animals. Taken together, these results indicate that the impairment of VSCR control of RSNA in the SHR model of hypertension correlates better with the magnitude of cardiac hypertrophy than the level of arterial pressure.

Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone

Inhibition of aldosterone synthase, the key enzyme in aldosterone formation, could be an alternative strategy for mineralocorticoid-receptor antagonists in congestive heart failure (CHF), but its effect in CHF is unknown. We compared, in rats with CHF, the effects of a 7 day and a 12 week treatment with the aldosterone synthase inhibitor FAD286 (4 mg kg(-1) day(-1)) with those induced by spironolactone (80 mg kg(-1) day(-1)). FAD286/spironolactone increased cardiac output without modifying arterial pressure. Long-term FAD286 and spironolactone reduced left ventricular (LV) end-diastolic pressure, LV relaxation constant, and LV dilatation, and these effects were more marked with FAD286, whereas both drugs reduced LV hypertrophy and collagen accumulation to the same extent. Long-term FAD286/spironolactone prevented CHF-related enhancement in LV ACE and reduction in LV ACE-2, but only FAD286 prevented the reduction in LV AT(2) receptors. FAD286, but not long-term spironolactone, reduced the CHF-related enhancements in LV reactive oxygen species, reduced-oxidized glutathione ratio, and aortic nicotinamide adenine dinucleotide phosphate oxidase activity. FAD286 normalized the CHF-induced impairment of endothelium-dependent vasodilatation. In experimental CHF, FAD286 and spironolactone improve LV haemodynamics, remodelling, and function, but only FAD286 persistently normalizes LV 'redox status'. These results suggest that aldosterone synthase inhibition is a potential therapeutic strategy for the treatment of CHF.

A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis

The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis. Effects of eplerenone on LV diastolic function and progression of valve stenosis were also evaluated. Sixty-five asymptomatic patients with a peak aortic valve velocity >3.0 m/s and normal LV function were randomized double blind to eplerenone, 100 mg daily (n = 33), or placebo (n = 32) for a median of 19 (interquartile range 15 to 25) months. Cardiac magnetic resonance imaging and echocardiography were performed and N-terminal pro-brain natriuretic peptide was measured at baseline and follow-up. Symptomatic deterioration occurred in 13 subjects randomized to eplerenone and 11 to placebo (P = .34). Change in LV mass index (mean change +/- SD -0.3 +/- 14.6 vs +5.1 +/- 15 g/m(2) per year, P = .3), LV ejection fraction (+0.0% +/- 5.7% vs +0.8% +/- 5.7% per year, P = .9), and LV end-systolic volume index (-1.2 +/- 9 vs +0.04 +/- 12 mL/m(2) per year, P = .8) were small and similar for patients randomized to eplerenone and placebo, respectively. Decrease of aortic valve area (-0.11 +/- 0.22 vs -0.18 +/- 0.24 cm(2)/y, P = .2), worsening of LV diastolic dysfunction by echo-Doppler (E/E' +0.49 +/- 0.7 vs +1.32 +/- 2.0/year, P = .4), increase in the plasma level of N-terminal pro-brain natriuretic peptide (+63% vs +12% per year, P = .1), and decline in physical function score (9 +/- 34 vs 12 +/- 37/year, P = .7) were similar for subjects randomized to eplerenone and placebo, respectively. In asymptomatic patients with moderate-severe aortic stenosis, eplerenone did not slow onset of LV systolic or diastolic dysfunction, decrease LV mass, or reduce progression of valve stenosis.

Congenic expression of tissue inhibitor of metalloproteinase in Dahl-salt sensitive hypertensive rats is associated with reduced LV hypertrophy

Although congenic translocation of a segment from chromosome 10 from Lewis rat, containing an extracellular proteinase inhibitor gene, decreased blood pressure in Dahl-salt sensitive (DSS) rats, the relationship between the levels of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and cardiac function was unclear. In this study we investigated the cardiac effects of congenic translocation of a segment from chromosome 10 from Lewis rat, containing an extracellular proteinase inhibitor gene, in Dahl-salt sensitive rats. To test the hypothesis that left ventricular (LV) hypertrophy in DSS rats was due to high MMP and low TIMP levels and the decrease in blood pressure in congenic rats was associated with increase in proteinase inhibitor expression, cardiac function and levels of MMP and TIMP were determined in 16 weeks male DSS (D), Lewis (L) and congenic (CL-10) rats. Cardiac function was assessed by electrocardiography, echocardiography and a Millar catheter in LV cavity. LV MMP and TIMP levels were measured by Q-RT-PCR and Western blot analyses. In L, D and CL-10 rats, heart weight/body weight (g/g) were 3.73 ± 0.06, 4.45 ± 0.04 and 3.35 ± 0.05 × 10−3, respectively, suggesting significant (p < 0.05) LV hypertrophy (LVH) in D group. The ST duration was longer in D group compared with L group, suggesting coronary vasospasm, but normalized in CL-10 rats. The fractional shortening and ejection fraction were decreased in D group as compared with L group, but normalized in CL-10 groups. LV diameter was increased in D group as compared to L group, but normalized in CL-10 groups. The levels of MMP-9 were higher and TIMP were lower in D as compared to L groups, but normalized in CL-10 rats. Compared with control non-congenic Dahl rats, congenic rats exhibited lower blood pressure, amelioration of LV remodelling and dysfunction, as well as coronary abnormalities. In addition, congenic animals exhibited reduced myocardial expression of MMP-9, but increased expression of MMP-2 and TIMP-4 compared to non congenic animals. We concluded that the congenic transfer of TIMP ameliorated LV hypertrophy and cardiac dysfunction.

Pioglitazone, a Thiazolidinedione Derivative, Attenuates Left Ventricular Hypertrophy and Fibrosis in Salt-Sensitive Hypertension

Thiazolidinediones, which stimulate peroxisome proliferator-activated receptor gamma, have been shown to prevent cardiovascular injury. However, little is known about their effects on salt-sensitive hypertension. We thus investigated whether or not pioglitazone affects left ventricular (LV) hypertrophy in Dahl salt-sensitive rats, then compared its effects to those of an angiotensin II receptor blocker, candesartan. Rats were used at 16 weeks of age after they had been fed either a low-salt (0.3%; DSL) or high-salt (8%; DSH) diet for 10 weeks; some of the DSH rats were treated with pioglitazone (10 mg/kg/day) or candesartan (4 mg/kg/day). Both drugs decreased the elevated blood pressure in DSH rats, although it was still higher than in DSL rats. Both drugs decreased plasma insulin levels, but neither affected plasma glucose levels. The thiobarbituric acid reactive substance level in the LV was decreased by both drugs. LV hypertrophy evaluated by echocardiography in DSH rats was nearly normalized by both drugs, whereas only candesartan decreased LV diameter. In histological analysis, both drugs ameliorated LV fibrosis and myocardial cell hypertrophy. Both drugs decreased elevated gene expression levels of transforming growth factor-beta1 and collagen type I, although the pioglitazone action was slightly modest. The metalloproteinase activity was increased in DSH rats, but both drugs decreased this level. Taken together, these findings indicate that pioglitazone reduced LV hypertrophy and fibrosis in salt-sensitive hypertension. Improvement in blood pressure, insulin level, and oxidative stress may be associated with this beneficial action of pioglitazone.

A High Fat Diet, But Not a High Sucrose Diet, Prevents Pressure Overload Induced Cardiac Dysfunction and Hypertrophy

Currently, a high carbohydrate/low fat diet is recommended to prevent cardiovascular disease; however the effect of dietary fat and carbohydrate on the left ventricular (LV) adaptation to pressure overload is still unclear. Male Wistar rats were fed standard chow (SC, 52% cal from cornstarch), high sugar (HS, 60% cal from sucrose) or high fat (HF, 60% from fat). After 1 week on the diet rats underwent abdominal aorta banding (AB) or sham surgery (n=9-11/group). LV function was assessed by echocardiography before surgery and after 8 wks. There were no differences in these parameters between the groups prior to surgery and body weight was not different among group throughout study. As show in the table, AB caused significant increase in LV mass, LV end systolic volume (sV) and decline in ejection fraction (EF) and velocity of circumferential flow (Vcf) in both standard and high sucrose chows. High fat prevented AB induced effects on LV function and blunted the increase in LV mass. In conclusion, high fat feeding prevented pressure overload induced cardiac contractile dysfunction and reduced LV hypertrophy. High sucrose feeding did not prevent the effects of pressure overload on the LV.

EFFECT OF ANTIHYPERTENSIVE THERAPY BASED ON NEW METHOD OF INDIVIDUAL CHOICE OF DRUGS ON LEFT VENTRICULAR HYPERTROPHY IN ELDERLY PATIENTS

Aim. To study the effects of antihypertensive therapy based on consideration of individual heart rhythm variability (HRV) on left ventricular hypertrophy (LVH) in hypertensive elderly patients. Material and methods. 60 hypertensive elderly patients with LVH were included in the study. They were split in two groups (30 people in each one). Patients of the group-I had common antihypertensive therapy. Patients of group-II received medications prescribed with consideration of individual heart rate variability. Holter monitoring with analysis of HRV, 24-hour blood pressure monitoring and ultrasonography were conducted initially and 18 months after treatment beginning. Results. BP control was reached in the majority of patients of both groups. The patients of group-II in comparison with patients of group-I had reduction of low- high frequency power ratio (LF/HF) and higher rate of LVH reduction. Relationship between LVH dynamics and ratio LF/HF was found. Conclusion. Arterial hypertension therapy considering individual HRV contributes in LVH reduction in elderly patients.

Left Atrial Size and Risk of Major Cardiovascular Events During Antihypertensive Treatment

The influence of left atrial size on cardiovascular events during antihypertensive treatment has not been reported previously from a long-term, prospective, randomized hypertension treatment trial. We recorded left atrial diameter by annual echocardiography and cardiovascular events in 881 hypertensive patients (41% women) with electrocardiographic left ventricular hypertrophy aged 55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Study. During follow-up, a total of 88 primary end points (combined cardiovascular death, myocardial infarction, or stroke) occurred. In Cox regression, baseline left atrial diameter/height predicted incidence of cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per cm/m]; P=0.042) adjusted for significant effects of Framingham risk score and history of atrial fibrillation. Greater left atrial diameter reduction during follow-up was associated with greater reduction in left ventricular hypertrophy, absence of new-onset atrial fibrillation or mitral regurgitation during follow-up, and losartan-based treatment (B=-0.13+/-0.03 cm/m; P<0.001) in multiple linear regression, adjusting for baseline left atrial diameter/height. However, in time-varying Cox regression analysis, left atrial diameter reduction was not independent of left ventricular hypertrophy regression in predicting cardiovascular events during follow-up. In conclusion, left atrial diameter/height predicts risk of cardiovascular events independent of other clinical risk factors in hypertensive patients with left ventricular hypertrophy and may be useful in pretreatment clinical assessment of cardiovascular risk in these patients.