Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Left ventricular function early after aortic valve replacement for aortic regurgitation: Assessment by gated radionuclide ventriculography

This study characterizes left ventricular performance early after aortic valve replacement for severe isolated aortic regurgitation. Gated radionuclide ventriculography studies in 13 patients showed that left ventricular end-diastolic volume was reduced after surgery and that ejection fraction dropped significantly. Despite the fall in ejection fraction, the postoperative cardiac index was significantly greater than the preoperative value. Radionuclide ventriculography is a useful and reliable means of noninvasively assessing left ventricular function soon after aortic valve replacement for aortic regurgitation.     

Implantable cardioverter defibrillator: an update

Automatic implantable cardioverter defibrillator is now a well established therapy to prevent sudden cardiac death. In secondary prevention (patients with a previous cardiac arrest) defibrillator can be considered as a class I indication, if there is no transient or reversible cause. The level of proof is A. in primary prevention the defibrillator is indicated in coronary artery disease patients with or without symptoms of mild to moderate heart failure (NYHA II or III), an ejection fraction lower than 30 %, measured at least one month after a myocardial infarction and 3 months after a revascularisation, surgery or angioplasty (level of proof B). It is also indicated in symptomatic spontaneous sustained ventricular tachycardias with underlying heart disease (level of proof B), in patients with spontaneous sustained ventricular tachycardia, poorly tolerated, without underlying heart disease for which pharmacological treatment or ablation can not be performed or failed (level of proof B). Finally it is also indicated in patients with syncope of unknown cause with sustained ventricular tachycardia or inducible ventricular fibrillation, with an underlying heart disease (level of proof B). The guidelines proposed by the different societies have also proposed class IIa recommendations which are the following: coronary artery disease patients with left ventricular dysfunction (ejection fraction between 31 or 35 %) measured at least one month after a myocardial infarction and 3 months after a revascularisation with an inducible ventricular arrhythmia. It can be also indicated in idiopathic dilated cardiomyopathies with an ejection fraction lower than 30% and NYHA class II or III. It can be also indicated in familial or inherited conditions with a high risk of sudden cardiac death by ventricular fibrillation without any other efficient known treatment and finally in heart failure patients remaining symptomatic, in class III or IV NYHA, with an optimal medical therapy, an ejection fraction lower than 35 % and a QRS complex duration higher than 120 ms: in this case it is an indication of cardiac resynchronization therapy device associated to the defibrillator. All these class IIa indications have a level of proof B.     

Combined pulmonary stenosis and insufficiency preserves myocardial contractility in the developing heart of growing swine at midterm follow-up.

This study was conducted to determine the effects of chronic combined pulmonary stenosis and pulmonary insufficiency (PSPI) on right (RV) and left ventricular (LV) function in young, growing swine. Six pigs with combined PSPI were studied, and data were compared with previously published data of animals with isolated pulmonary insufficiency and controls. Indexes of systolic function (stroke volume, ejection fraction, and cardiac functional reserve), myocardial contractility (slope of the end-systolic pressure-volume and change in pressure over time-end-diastolic volume relationship), and diastolic compliance were assessed within 2 days of intervention and 3 mo later. Magnetic resonance imaging was used to quantify pulmonary insufficiency and ventricular volumes. The conductance catheter was used to obtain indexes of the cardiac functional reserve, diastolic compliance, and myocardial contractility from pressure-volume relations acquired at rest and under dobutamine infusion. In the PSPI group, the pulmonary regurgitant fraction was 34.3 +/- 5.8%, the pressure gradient across the site of pulmonary stenosis was 20.9 +/- 20 mmHg, and the average RV peak systolic pressure was 70% systemic at 12 wk follow-up. Biventricular resting cardiac outputs and cardiac functional reserves were significantly limited (P < 0.05), LV diastolic compliance significantly decreased (P < 0.05), but RV myocardial contractility significantly enhanced (P < 0.05) compared with control animals at 3-mo follow-up. In the young, developing heart, chronic combined PSPI impairs biventricular systolic pump function and diastolic compliance but preserves RV myocardial contractility.     

Sudden death and its predictors in myocardial infarction survivors in an Indian population

ObjectiveThis study was conducted to assess the incidence of sudden cardiac death (SCD) in post myocardial infarction patients and to determine the predictive value of various risk markers in identifying cardiac mortality and SCD.MethodsLeft ventricular function, arrhythmias on Holter and microvolt T wave alternans (MTWA) were assessed in patients with prior myocardial infarction and ejection fraction ≤ 40%. The primary outcome was a composite of cardiac death and resuscitated cardiac arrest during follow up. Secondary outcomes included total mortality and SCD.ResultsFifty-eight patients were included in the study. Eight patients (15.5%) died during a mean follow-up of 22.3 ± 6.6 months. Seven of them (12.1%) had SCD. Among the various risk markers studied, left ventricular ejection fraction (LVEF) ≤ 30% (Hazard ratio 5.6, 95% CI 1.39 to 23) and non-sustained ventricular tachycardia (NSVT) in holter (5.7, 95% CI 1.14 to 29) were significantly associated with the primary outcome in multivariate analysis. Other measures, including QRS width, heart rate variability, heart rate turbulence and MTWA showed no association.ConclusionsAmong patients with prior myocardial infarction and reduced left ventricular function, the rate of cardiac death was substantial, with most of these being sudden cardiac death. Both LVEF ≤30% and NSVT were associated with cardiac death whereas only LVEF predicted SCD. Other parameters did not appear useful for prediction of events in these patients. These findings have implications for decision making for the use of implantable cardioverter defibrillators for primary prevention in these patients.     

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury.     

微创小切口主动脉瓣置换术对主动脉瓣狭窄患者临床效果、心功能及术后时间的影响

目的:探讨微创小切口主动脉瓣置换术对主动脉瓣狭窄患者临床效果、心功能及术后时间的影响。方法:选择2017年5月-2018年11月我院收治的98例患者,随机分为观察组(n=49)和对照组(n=49)。对照组患者给予传统开胸主动脉瓣置换术,观察组患者给予微创小切口主动脉瓣置换术。观察比较两组临床疗效,心功能指标变化,术后时间变化。结果:观察组有效率为93.88%,明显高于对照组71.43%,两组疗效比较差异有统计学意义(P0.05)。观察组术后左室射血分数(LVEF)、左室舒张末期直径(LVEDD)、平均跨瓣压差(MVPG)明显低于对照组,差异均具有统计学意义(P0.05);观察组术室间隔厚度(IVST)高于对照组,但差异无统计学意义(P0.05)。观察组术后机械通气时间,ICU时间,住院时间明显低于对照组,差异均具有统计学意义(P0.05)。结论:微创小切口主动脉瓣置换术治疗主动脉瓣狭窄临床疗效显著,可有效改善患者心功能,缩短治疗时间,提高患者生活质量,值得推广应用。     

Occult aortic stenosis as cause of intractable heart failure

During a three-year period 10 patients with critical aortic stenosis were referred to a cardiac referral centre with symptoms and signs of intractable cardiac failure and low cardiac output. In nine patients the correct diagnosis was not suspected at the referring hospital, and in the remaining patient the true severity of the aortic stenosis was not appreciated and cardiomyopathy was suggested as an additional diagnosis. The most common referral diagnoses were severe mitral regurgitation (four patients), congestive cardiomyopathy (two patients), or both (three patients). Only two patients had soft ejection systolic murmurs at the base of the heart radiating into the neck, and such a murmur appeared in a third patient during medical treatment. The carotid pulses were of small volume but the characteristic slow-rising, anacrotic nature of the pulse could not be appreciated clinically. The diagnosis was suspected in nine patients because of aortic valve calcification detected by lateral chest x-ray examination in seven patients and by x-ray screening of the heart in two, and because of abnormal aortic valve echoes in the echocardiogram of all five patients in whom the aortic valve could be seen. Eight patients underwent aortic valve replacement despite seemingly poor preoperative left ventricular function. Three patients died, of whom two had severe coexistent coronary artery disease. The five survivors all returned to normal lives and needed little or no medication.Critical aortic stenosis should be actively sought in patients with severe heart failure of unknown cause since surgery may enable them to resume their normal lives.     

Neurohormones in an ovine model of compensated postinfarction left ventricular dysfunction

Clinical heart failure, often the result of myocardial infarction, may be preceded by a period of compensated left ventricular impairment. There is substantial need for an experimental model that reflects this human condition. In sheep, coronary artery ligation produced consistent left ventricular anteroapical myocardial infarctions resulting in chronic (5 wk), stable hemodynamic changes compared with sham controls, including reductions in ejection fraction (51 +/- 2 vs. 30 +/- 5%, P < 0.001), cardiac output (6.3 +/- 0.2 vs. 5.1 +/- 0.2 l/min, P < 0.01), and arterial pressure (93 +/- 2 vs. 79 +/- 3 mmHg, P < 0.001), and increases in cardiac preload (left atrial pressure, 3.3 +/- 0.1 vs. 8.3 +/- 1.3 mmHg, P < 0.001). These changes were associated with acute and sustained increases in plasma concentrations of atrial natriuretic peptide (ANP; 5 wk, 11 +/- 2 vs. 27 +/- 5 pmol/l, P < 0.001), brain natriuretic peptide (BNP; 3 +/- 0.2 vs. 11 +/- 2 pmol/l, P < 0.001), and amino-terminal pro-brain natriuretic peptide (NT-BNP; 17 +/- 3 vs. 42 +/- 12 pmol/l, P < 0.001). Significant correlations were observed between plasma levels of the natriuretic peptides (ANP, day 7 to week 5 samples; BNP and NT-BNP, day 1 to week 5 samples) and changes in left ventricular volumes and ejection fraction. In contrast, renin activity, aldosterone, catecholamines, and endothelin were not chronically elevated postinfarction and were not related to indexes of ventricular function. Coronary artery ligation in sheep produces the pathological, hemodynamic, and neurohormonal characteristics of compensated left ventricular impairment secondary to myocardial infarction. Plasma concentrations of the cardiac natriuretic peptides are sensitive markers of left ventricular dysfunction. This is a reproducible model that reflects the clinical condition and should prove suitable for investigating the pathophysiology of, and experimental therapies in, early left ventricular dysfunction.     

Abnormal function and glucose metabolism in the type-2 diabetic db/db mouse heart

This study examined cardiac function and glucose metabolism in the 6-month-old db/db mouse, a model of type-2 diabetes. Cine magnetic resonance spectroscopy (MRI) was used to measure cardiac function in vivo. The db/db mice had decreased heart rates (17%, p<0.01) and stroke volumes (21%, p<0.05) that resulted in lower cardiac output (35%, p<0.01) than controls. Although there was no difference in ejection fraction between the 2 groups, db/db mouse hearts had a 35% lower maximum rate of ejection (p<0.01) than controls. In a protocol designed to assess maximal insulin-independent glucose uptake, hearts were isolated and perfused in Langendorff mode and subjected to 0.75 mL.min(-1).(g wet mass)(-1) low flow ischemia for 32 min. Glucose uptake during ischemia was 21% lower than in controls, and post-ischemic recovery of cardiac function was decreased by 30% in db/db mouse hearts (p<0.05). Total cardiac GLUT 4 protein was 56% lower (p<0.01) in db/db mice than in controls. In summary, the db/db mouse has abnormal left ventricular function in vivo, with impaired glucose uptake during ischemia, leading to increased myocardial damage.     

Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy

The clinical course of patients with dilated cardiomyopathy (DCM) varies from cardiac recovery to end stage heart failure. The etiology of this variability is largely unknown. In this study, we investigated the impact of coding polymorphisms of the innate immune protein Toll-like receptor 4 (TLR4) on left ventricular performance in patients with DCM. Two variants of TLR4 (rs4986790, TLR4 c.1187A→G, p.299D→G and rs4986791,TLR4 c.1487C→T, p.T399I) were investigated in 158 patients with DCM. Other reasons for heart failure were excluded by coronary angiography, myocardial biopsy, and echocardiography. Risk factors, age, gender, or treatment did not differ among the groups. At the follow-up evaluation (median 4.0-5.4 months), patients carrying the TLR4 wild type gene displayed cardiac recovery under intense medical heart failure therapy indexed by reduced left ventricular dilation, improved left ventricular ejection fraction, and reduced NT-probrain natriuretic peptide blood level when compared with the initial evaluation. In contrast, patients carrying both the rs4986790 and the rs4986791 variant showed significantly reduced improvement of left ventricular ejection fraction (p = 0.006) and left ventricular dilation (p = 0.015) at the follow-up evaluation when compared with carriers of the wild type gene under the same treatment conditions. In addition, NT-probrain natriuretic peptide level in carriers of both TLR4 variants did not change significantly at the follow up when compared with the first evaluation. Among patients with DCM, the presence of the TLR4 variants rs4986790 and rs4986791 predicts impaired cardiac recovery independently of medical treatment or cardiac risk factors.     

Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart

Aging and diabetes mellitus (DM) both affect the structure and function of the myocardium, resulting in increased collagen in the heart and reduced cardiac function. As part of this process, hyperglycemia is a stimulus for the production of advanced glycation end products (AGEs), which covalently modify proteins and impair cell function. The goals of this study were first to examine the combined effects of aging and DM on hemodynamics and collagen types in the myocardium in 12 dogs, 9-12 yr old, and second to examine the effects of the AGE cross-link breaker phenyl-4,5-dimethylthazolium chloride (ALT-711) on myocardial collagen protein content, aortic stiffness, and left ventricular (LV) function in the aged diabetic heart. The alloxan model of DM was utilized to study the effects of DM on the aging heart. DM induced in the aging heart decreased LV systolic function (LV ejection fraction fell by 25%), increased aortic stiffness, and increased collagen type I and type III protein content. ALT-711 restored LV ejection fraction, reduced aortic stiffness and LV mass with no reduction in blood glucose level (199 +/- 17 mg/dl), and reversed the upregulation of collagen type I and type III. Myocardial LV collagen solubility (%) increased significantly after treatment with ALT-711. These data suggest that an AGE cross-link breaker may have a therapeutic role in aged patients with DM.     

Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker

It is not known how the angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) attenuate heart failure (HF) in viable ischemic hearts. To assess HF in a rat coronary stenosis (CS) model, we administered vehicle and quinapril or candesartan (or both) orally for 12 wk. Compared with the sham group, the vehicle group showed impaired myocardial perfusion, impaired coronary endothelial nitric oxide (NO) function in vitro, exhausted myocardial mitochondrial respiration, larger left ventricular (LV) dimensions and lower ejection fraction, lower LV rate of pressure development over time (dP/dt), lower slopes of LV end-systolic pressure-dimension relations (ESPDRs), and increased myocardial fibrosis. Treatment with quinapril or candesartan ameliorated these parameters without modifying the epicardial CS severity. Moreover, their combination maintained similar myocardial perfusion, despite a trend toward lower blood pressure, and showed distinctive neurohumoral modulation, normalized mitochondrial respiration, and increased ESPDR slopes. Thus improved myocardial blood flow and coronary flow reserve by quinapril or candesartan are the key to alleviate CS-induced HF, and their combination may have a therapeutic significance partly through ameliorated mitochondrial respiration and improved LV systolic function.     

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia.

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.     

Clinical outcome of high-risk patients with severe aortic stenosis and reduced left ventricular ejection fraction undergoing medical treatment or TAVI

Introduction

Reduced left ventricular function in patients with severe symptomatic valvular aortic stenosis is associated with impaired clinical outcome in patients undergoing surgical aortic valve replacement (SAVR). Transcatheter Aortic Valve Implantation (TAVI) has been shown non-inferior to SAVR in high-risk patients with respect to mortality and may result in faster left ventricular recovery.

Methods

We investigated clinical outcomes of high-risk patients with severe aortic stenosis undergoing medical treatment (n = 71) or TAVI (n = 256) stratified by left ventricular ejection fraction (LVEF) in a prospective single center registry.

Results

Twenty-five patients (35%) among the medical cohort were found to have an LVEF≤30% (mean 26.7±4.1%) and 37 patients (14%) among the TAVI patients (mean 25.2±4.4%). Estimated peri-interventional risk as assessed by logistic EuroSCORE was significantly higher in patients with severely impaired LVEF as compared to patients with LVEF>30% (medical/TAVI 38.5±13.8%/40.6±16.4% versus medical/TAVI 22.5±10.8%/22.1±12.8%, p <0.001). In patients undergoing TAVI, there was no significant difference in the combined endpoint of death, myocardial infarction, major stroke, life-threatening bleeding, major access-site complications, valvular re-intervention, or renal failure at 30 days between the two groups (21.0% versus 27.0%, p = 0.40). After TAVI, patients with LVEF≤30% experienced a rapid improvement in LVEF (from 25±4% to 34±10% at discharge, p = 0.002) associated with improved NYHA functional class at 30 days (decrease ≥1 NYHA class in 95%). During long-term follow-up no difference in survival was observed in patients undergoing TAVI irrespective of baseline LVEF (p = 0.29), whereas there was a significantly higher mortality in medically treated patients with severely reduced LVEF (log rank p = 0.001).

Conclusion

TAVI in patients with severely reduced left ventricular function may be performed safely and is associated with rapid recovery of systolic left ventricular function and heart failure symptoms.     

Congenital Aortic Stenosis: Some Observations on the Natural History and Clinical Assessment

Three hundred patients, 30 years of age or under, with the clinical diagnosis of aortic stenosis were reviewed to provide information on the accuracy of clinical assessment and the natural history of the condition when left untreated. Sudden death was uncommon and occurred only in patients with clinical evidence of severe obstruction. In infants, the early presentation and lethal nature of aortic stenosis appeared to result from the presence of additional cardiac lesions. Correlation of clinical assessment with hemodynamic data in 83 patients indicated that important stenosis was present if the systolic murmur was accompanied by a thrill and associated with an increased left ventricular impulse, decreased brachial artery pulse pressure, or left ventricular hypertrophy on the electrocardiogram. The site of obstruction could not be established with certainty by clinical examination, but an early systolic ejection click was strong evidence against subvalvular stenosis.     

Myocardial Salvage is Reduced in Primary PCI-Treated STEMI Patients with Microvascular Obstruction,Demonstrated by Early and Late CMR

Objectives

This study evaluates the association between microvascular obstruction and myocardial salvage, determined by cardiac magnetic resonance performed both in the acute stage of myocardial infarction and after 4 months.

Methods

In patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention, myocardial salvage, infarct size, left ventricular volumes, and ejection fraction were assessed by early (1–4 days) and follow-up (4 months) cardiac magnetic resonance. These variables were related to the presence or absence of microvascular obstruction at early investigation. Myocardial salvage was determined by: (1) myocardium at risk and infarct size measured in the acute stage and (2) myocardium at risk, measured acutely, and infarct size measured after 4 months. Multivariate analyses were performed, adjusting for clinical confounders at baseline.

Results

Microvascular obstruction was present in 49 of 94 included patients, (52%). Myocardial salvage was significantly reduced in patients with microvascular obstruction, compared to those without: 23% vs. 38%, measured acutely, and 39.8% vs. 65.4%, after 4 months (p<0.001). The presence of microvascular obstruction was significantly and independently associated with large infarct size, lower left ventricular ejection fraction, and larger left ventricular end-systolic volume.

Conclusion

The presence of microvascular obstruction demonstrated by cardiac magnetic resonance early after infarction was associated with impaired myocardial salvage. This association was more marked when based on measurement of infarct size after 4 months compared to assessment in the acute stage.     

Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats

To elucidate the molecular mechanism underlying estrogen-mediated cardioprotection in left ventricular (LV) hypertrophy and remodeling, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized, aortic-banded rats. Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. Effects on LV morphology and function were assessed using echocardiography, and expression of protein levels was determined by Western blot analysis. The heart-to-body weight ratio was most significantly increased in the OVX-pressure overload (PO) group compared with the OVX group and in the PO group compared with sham. The LV weight-to-body weight ratio was also significantly increased in the OVX-PO group compared with the OVX group and in the PO group compared with sham. The most significant increases in LV end diastolic pressure, LV developed pressure, and +/-dp/dt(max) were observed in the OVX-PO group compared with the OVX group and represent compensatory phenotypes against hypertrophy. Both endothelial nitric oxide (eNOS) synthase expression and activity was markedly reduced in the OVX-PO group, and protein kinase B (Akt) activity was largely attenuated. Marked breakdown of dystrophin was also seen in hearts of OVX-PO groups. Finally, significantly increased mortality was observed in the OVX-PO group following chronic isoproterenol administration. Our results demonstrate that rats subjected to ovariectomy are unable to compensate for hypertrophy, showed deteriorated heart function, and demonstrated increased mortality. Simultaneous impairment of eNOS and Akt activities and reduced dystrophin by ovariectomy likely contribute to cardiac decompensation during PO-induced hypertrophy in ovariectomized rats.     

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

ABSTRACT: BACKGROUND: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.     

Elevated Plasma Soluble ST2 Is Associated with Heart Failure Symptoms and Outcome in Aortic Stenosis

B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74±13 years; 59 asymptomatic, 69%) with AS (<1.5 cm²) and preserved left ventricular ejection fraction who were followed-up for 26±16 months. Both BNP and sST2 were associated with NYHA class but sST2 (>23 ng/mL, AUC = 0.68, p<0.01) was more accurate to identify asymptomatic patients or those who developed symptoms during follow-up. sST2 was independently related to left atrial index (p<0.0001) and aortic valve area (p = 0.004; model R² = 0.32). A modest correlation was found with BNP (r = 0.4, p<0.01). During follow-up, 29 asymptomatic patients (34%) developed heart failure symptoms. With multivariable analysis, peak aortic jet velocity (HR = 2.7, p = 0.007) and sST2 level (HR = 1.04, p = 0.03) were independent predictors of cardiovascular events. In AS, sST2 levels could provide complementary information regarding symptomatic status, new onset heart failure symptoms and outcome. It might become a promising biomarker in these patients.