Drugs acting on the heart: heart failure and coronary insufficiency

Heart failure (HF) and coronary insufficiency are common amongst surgical and critical care patients. Both are chronic conditions interrupted by acute episodes. HF activates neurohormonal mechanisms that worsen renal and cardiac function. Acute heart failure (AHF) commonly presents with dyspnoea as a consequence of systolic and/or diastolic dysfunction. Goals of treatment are symptom relief, to maintain tissue perfusion and optimize cardiac function. Diuretics and vasodilators are used early; positive inotropic drugs are reserved for when other treatment has failed. Chronic heart failure (CHF) is treated using changes in lifestyle and drugs to manage symptoms. ACE inhibitors and beta-blockers are effective in systolic heart failure and are associated with improved mortality. HF with preserved ejection fraction (HFPEF) is less responsive to drug therapy, though outcomes are better than for systolic HF. Coronary insufficiency occurs because of an imbalance of myocardial oxygen balance, leading to symptoms of ischaemic heart disease (IHD). Treatment goals are maintaining coronary blood flow and reducing myocardial oxygen demand. Beta-blockers and anti-platelet drugs improve outcomes; modern anti-platelets are more effective but are associated with risks of haemorrhage. Statins are effective for primary and secondary prevention of myocardial infarction; they have additional anti-inflammatory properties.     

Drugs acting on the heart: heart failure and coronary insufficiency

Heart failure (HF) and coronary insufficiency are common amongst surgical and critical care patients. Both are chronic conditions interrupted by acute episodes. HF activates neurohormonal mechanisms that worsen renal and cardiac function. Acute heart failure (AHF) commonly presents with dyspnoea as a consequence of systolic and/or diastolic dysfunction. Goals of treatment are symptom relief, maintenance of tissue perfusion, and optimizing cardiac function. Diuretics and vasodilators are used early; inotropes are reserved for when other treatment has failed.Chronic heart failure (CHF) is treated by changes in lifestyle and drugs to manage symptoms. ACE inhibitors and β-blockers are effective in systolic heart failure and are associated with improved mortality. HF with preserved ejection fraction (HFPEF) is less responsive to drug therapy, though outcomes are better than for systolic HF.Coronary insufficiency occurs when myocardial oxygen delivery is inadequate, leading to symptoms of ischaemic heart disease (IHD). Treatment goals are maintaining coronary blood flow and reducing myocardial oxygen demand. β-blockers and anti-platelet drugs improve outcomes; modern anti-platelets are more effective but associated with risks of haemorrhage. Statins are effective for primary and secondary prevention of myocardial infarction; they have additional anti-inflammatory properties.     

Drugs acting on the heart: heart failure and coronary insufficiency

Heart failure (HF) and coronary insufficiency are common among intensive care patients or those undergoing surgery. Both conditions can present as an acute decompensated state with high mortality or with a more stable, chronic course. Although similar drugs can be used to treat both conditions, an understanding of the respective pathological processes enables better targeting of treatment. Several drugs have been recently developed for HF and coronary insufficiency. It is increasingly appreciated that HF is not a single entity: the pathophysiology, treatment and prognosis depend on whether systolic or diastolic dysfunction predominates, and whether the condition is stable and compensated or acute and decompensated. Acute decompensated heart failure (ADHF) is treated with diuretics, vasodilators and positive inotropes in some cases. It is better to treat decompensated systolic HF with reduced left ventricular ejection fraction (LVEF; < 40%) with arterial dilators, whereas diastolic HF with intact LVEF responds better to venodilators. After an episode of ADHF, treatment for chronic HF (diuretics, angiotensin-converting enzyme inhibitors (ACEIs) and β-blockers unless contraindicated) should be initiated before hospital discharge and continued. ACEIs and β-blockers slow the progression of chronic HF and reduce mortality. Ischaemic heart disease is managed with nitrates, β-blockers, ACEIs, statins and anti-platelet drugs. In the acute coronary syndrome, thrombolytic agents are still used.     

Durable mechanical circulatory support in patients with heart failure with preserved ejection fraction

Only few patients with heart failure with preserved ejection fraction undergo durable mechanical circulatory support implantation. We identified three patients with heart failure with preserved ejection fraction who needed durable mechanical circulatory support as bridge-to-transplant therapy. In two patients with hypertrophic cardiomyopathy, the hypertrophic papillary muscles and myocardium were resected to allow for subsequent left ventricular assist device implantation. In one patient, all visible parts of the mitral valve were additionally resected. The third patient with restrictive cardiomyopathy underwent Berlin Heart Excor BVAD implantation with left atrial cannulation.     

非体外循环冠状动脉搭桥术在低射血分数冠心病患者中的应用

目的探讨非体外循环冠状动脉搭桥手术（OPCAB）对低射血分数（EF）冠心病患者的临床疗效。方法对我院心脏外科在2005年12月-2009年8月收治41例低射血分数的冠心病患者行OPCAB进行回顾性分析。全部患者均在全麻下行OPCAB手术。记录手术前EF,左室缩末内径（LVSD）、左室舒末内径（LVDD）与术后一周和三月复查结果进行比较;此外,测定手术前与手术后8小时肌酐（Cr）,尿素氮（BUN）,血小板计数（PLT）并进行比较。结果1例术后14h死于心低排出综合征,死亡率为2．43％,其余患者痊愈出院。术后一周EF、LVSD与术前相比虽未见明显变化（P〉0．05）。但LVDD明显缩小（P〈0．05）;术后三个月后复查心脏超声EF值明显提高（P〈0．05）,LVSD未见明显缩小（P〉0．05）,LVDD明显减小（P〈0．05）;出院时34例（85％）患者NYHA分级较手术前有1—2级不同程度的改善,37例（92．5％）患者CCS分级较手术前有1—2级不同程度的改善;手术前后Cr,BUN及PLT未见明显变化（P〉0．05）。术后30例患者随访1—2年,心绞痛症状消失,心肌缺血表现及活动耐力明显改善。结论低EF冠心病患者实施OPCAB避免或减少了体外循环损伤和缺血再灌注损伤,有良好的可行性和近期效果．而远期结果仍有待进一步观察．     

血清新碟呤与冠状动脉病变程度关系的临床研究

目的探讨冠心病患者血清新碟呤与冠状动脉病变程度的关系。方法对经冠状动脉造影确诊的86例冠心病患者,分为急性心肌梗死组21例,不稳定型心绞痛组35例,稳定型心绞痛组30例;30例冠状动脉造影正常者为对照组。采用酶联免疫吸附法测定其新碟呤水平,比较不同冠脉病变程度者血清值,分析与冠状动脉病变狭窄程度、病变支数的关系。结果新喋呤浓度在急性心肌梗死组和不稳定型心绞痛组中均高于稳定型心绞痛（P〈0.01）;但急性心肌梗死组与不稳定型心绞痛组、稳定型心绞痛和对照组之间差异无统计学意义（P〉0.05）。新喋呤浓度在单支、双支、三支病变组之间差异无统计学意义（P〉0.05）。结论新喋呤参与动脉粥样硬化斑块的发生、发展过程,可作为预测斑块稳定性的标志物。     

Impact of mitral insufficiency on reoperative coronary artery surgery in ischemic cardiomyopathy patients

Objective: To determine the impact of mitral insufficiency on survival after reoperative coronary artery bypass grafting (CABG) in ischemic cardiomyopathy patients. Methods: We retrospectively studied 891 (Initial 708, Redo 183) consecutive CABG patients (1993–2002) with ejection fraction (EF) 35% or less. Patient characteristics: mean age=67.0±10.5 yrs, men=77.1%, EF=26.4±7.4%, mean CCS=3.47±0.73, mean NYHA=3.50±0.68. There were 180 (Initial 141, Redo 39) patients with 3/4+mitral regurgitation (MR). Late survival statistics of cohorts were compiled using National Death Index. Results: At a mean follow-up period of 3 years, reoperative CABG with MR (Redo/MR+) survival was 41.7±9.2% (n=39), which was worse than reoperative CABG without MR (Redo/MR−) survival of 71.8±4.1% (n=144, P=0.0003), initial CABG with MR (Initial/MR+) survival of 68.5±4.2% (n=141, P=0.014) and initial CABG without MR (Initial/MR−) survival of 76.2±2.0% (n=567, P<0.0001). By multivariate analysis, congestive heart failure (P=0.029), 3/4+MR (P=0.044) were independent predictors of Redo late mortality. In contrast, renal failure on dialysis, stroke, no angina, age >65 yrs, absence of hypercholesterolemia, EF<26% but not 3/4+MR were independent predictors of Initial late mortality. In subset analysis, adverse impact of 3/4+MR on late survival was greatest in Redo with EF<26%. The 3- and 5-yr late survival were only 44.4 and 26.8% (P=0.041). Concomitant mitral valve repair (MVrep) was performed in 100 (Initial 75, Redo 25) patients. MVrep in Initial/MR+patients achieved similar late survival as Initial/MR− patients. MVrep did not produce the same late survival benefit in Redo/MR+ patients. Conclusions: (1) Mitral insufficiency has a greater survival impact on redo than initial CABG patients with ischemic cardiomyopathy. (2) Mitral insufficiency and congestive heart failure are the primary independent predictors of late survival following redo CABG. (3) Mitral repair has less neutralizing effect on late survival in redo than initial CABG patients.     

Longitudinal evaluation of ventricular ejection fraction and NT-proBNP across heart failure subgroups

Objectives: Left ventricular ejection fraction (EF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are important surrogate markers of cardiac function and wall stress. Randomized trials of heart failure (HF) have shown improvements in survival in patients with reduced EF (<40%, HFrEF) but not with preserved EF (≥50%, HFpEF) or mid-range EF (40-49%, HFmrEF). Limited information is available on the trajectory of EF in contemporary heart failure management programs (HFMPs).

Design: 201 HF patients consecutively enrolled 2010–2011 in the outpatient-based HFMP of Skåne University Hospital in Lund were included in the study. Probable etiology, EF, NT-proBNP and medications were assessed at baseline and 1 year after enrollment.

Results: HFrEF was the most common heart failure subgroup (78.1% of patients) in this HFMP, followed by HFmrEF (14.9%) and HFpEF (7.0%). The most common etiology was ischemic heart disease (IHD, 40.8%).

Complete recovery of EF (>50%) was rare (14.1% of patients with HFrEF and 26.7% with HFmrEF), some degree of improvement was observed in 57.7% and 46.7% of patients. LVEF improved on average 9.1% in patients with HFrEF (p?p?Conclusions: This study provides estimates of the improvement in LVEF and NT-proBNP that can be expected with contemporary management across subgroups of HF and different etiologies in a contemporary HFMP.     

Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.     

冠心病合并颈动脉狭窄的治疗

目的 探讨冠状动脉旁路移植术(CABG)和颈动脉内膜剥脱术(CEA)治疗冠心病合并颈动脉狭窄的治疗方法的选择.方法 2009年1月至2011年12月期间,首都医科大学附属北京安贞医院大血管中心23例冠心病合并颈动脉狭窄患者同期或分期行CABG和CEA治疗,男16例,女7例.年龄53 ～ 82岁,平均(65.9±4.0)岁.冠状动脉造影发现左主干病变3例,2支病变3例,3支病变17例.1例合并二尖瓣关闭不全.单侧颈动脉狭窄17例,双侧狭窄6例,直径狭窄≥70％.依据患者两处病变病情严重程度而采取冠状动脉旁路移植术(CABG)和颈动脉内膜剥脱术(CEA)同期或分期治疗,术后观察围手术期发生卒中、心肌梗死的及死亡情况,并随访.结果 7例患者同期行CEA和CABG,其中1例同时行二尖瓣置换;13例患者先期行CABG后行CEA;3例患者先行CEA后行CABG.围术期死亡1例(4.3％),无心绞痛、心肌梗死和卒中.随访6个月,随访期内患者未发生死亡、卒中、心绞痛及心肌梗死.结论 同期还是分期行CABG和CEA治疗冠心病合并颈动脉狭窄应根据患者具体情况而定,个性化治疗是降低手术风险的关键.     

连续1052例冠心病手术无死亡的临床经验

目的 总结冠心病外科治疗无死亡的临床经验.方法 回顾性分析2006年1月至2010年3月在阜外医院完成冠心病外科手术治疗1052患者例临床资料.结果 全组950例(90.3％)行非体外循环冠状动脉旁路移植术( OPCAB),102例(9.7％)行体外循环冠状动脉旁路移植术(on-pump CABG).术前患者EuroScore( 3.4±2.6)分,＞6分者127例(12.0％).平均旁路移植血管为(3.2±0.9)支,术后平均住院(7.7±2.5)天.术后并发症包括二次开胸探查14例,呼吸道感染8例,心功能不全IABP支持6例,急性肾功能不全5例.全组患者住院期间无死亡,均治愈出院.结论 制定个体化治疗措施,加强围术期管理,结合技术创新,冠心病手术结果满意.     

非体外循环冠状动脉旁路移植术治疗重症冠状动脉粥样硬化性心脏病

目的探讨非体外循环冠状动脉旁路移植术治疗重症冠状动脉粥样硬化性心脏病(冠心病)的可行性. 方法回顾分析2002年1月～12月37例重症冠心病的临床资料.均采用全麻,胸骨正中切口,游离左乳内动脉及大隐静脉.心脏稳定器局部固定心肌,显露目标冠状动脉,切开后置入冠状动脉内血液分流器.一般先做左乳内动脉与左冠状动脉前降支的吻合,其余血管桥先做桥血管与主动脉的近心端吻合,然后再做桥血管与冠状动脉的吻合. 结果全组病例均在非体外循环下完成手术,搭桥1～6支,(3.2±0.5)支.术后10 d死亡1例,其余36例未发生围术期心肌梗死,无呼吸功能不全、肾功能不全、脑血管意外等严重并发症. 结论在成熟的手术技术和严格的围手术期管理的条件下,非体外循环冠状动脉旁路移植术治疗重症冠心病可行.     

Significant benefits after renal transplantation in patients with chronic heart failure and chronic kidney disease

Background: Chronic heart failure (CHF) and chronic kidney disease (CKD) are serious medical conditions with significant morbidity and mortality and often coexist. Because of perioperative risks in these patients, they may not be considered a candidate for renal transplantation (RTx).

Material and methods: We compare retrospectively RTx outcomes [graft/patient survival, rejection rates and adverse cardiac events] in study group [low left ventricular ejection fraction (LVEF) ≤45% by echocardiogram, n?=?63] and control group [normal LVEF ≥50%, n?=?537] from a developing country.

Results: The mean EF was 35?±?5.6 and 57?±?3% for the study and control groups, respectively (p?Conclusion: RTx may play a role in reversing LV systolic dysfunction. Once thought by many to be a contraindication for renal transplantation, this appears not to be the case. The outcomes between the 2 groups are comparable and transplant is an option for even low EF patients.     

冠状动脉弥漫性病变并低射血分数患者的外科治疗

目的 探讨冠状动脉弥漫性病变并低射血分数患者的外科治疗方法与疗效.方法 冠状动脉弥漫性病变患者68例,依射血分数高低分为两组：组1,34例,男20例,女14例;年龄36 ～ 72岁,平均（59.3±7.0）岁;左室射血分数（LVEF） ＜40％.组2,34例,男24例,女10例;年龄38～79岁,平均（62.2±7.1）岁;40％≤LVEF＜ 50％.狭窄段＜5 mm,内膜剥脱术同期搭桥.狭窄段≥5 mm,狭窄近、远端各搭一支桥或序贯搭桥.结果 全组左心室舒张末径较术前明显减小[（52 ±2）mm vs （60 ±4）mm,t =7.32,P＜0.05）];LVEF较术前明显增高[（45±17）％vs （34±15）％,t=4.770,P＜0.05],与术前比较差异有统计学意义.手术前后左室舒张末径变化值[（12.4 ±5.6）mm vs （13.65 ±5.6）mm],两组比较差异无统计学意义（P＞0.05）.两组手术前后左室变化值[（12.24 ±5.6）mm vs（13.65±3.2）mm],两组比较差异无统计学意义（P＞0.05）;两组手术前后LVEF变化值[（10.12±3.6）％vs（10.32±5.6）％],两组比较差异无统计学意义（P＞0.05）.结论 外科治疗冠状动脉弥漫性病变并低射血分数患者安全、有效.     

Improvement in ejection fraction by nocturnal haemodialysis in end-stage renal failure patients with coexisting heart failure.

BACKGROUND: Congestive heart failure (CHF) is an independent risk factor for mortality in the end-stage renal disease (ESRD) population. Nocturnal haemodialysis (NHD), a novel mode of renal replacement therapy, may be more effective than conventional haemodialysis in reducing intravascular volume or in removing uraemic toxins with vasoconstrictor or myocardial depressant actions, and may, therefore, improve the left ventricular (LV) systolic function of patients with coexisting cardiac and renal failure. METHODS: To test this hypothesis, we determined, in six patients (mean age+/-SD: 49.5+/-9 years), blood pressure (BP), ejection fraction (EF: radionucleotide angiography), left ventricular mass index (LVMI: echocardiography), LV fractional shortening (FS), and extracellular fluid volume (ECFV: bioelectrical impedance): before and after a mean of 3.2+/-2.1 years following conversion from conventional dialysis (3 days/week x 4 h) to NHD (6 nights/week x 8-10 h). RESULTS: There were significant reductions in systolic and mean arterial BP (138+/-10 to 120+/-9 mmHg, P=0.04; 99+/-6 to 86+/-7 mmHg, P=0.01). There was a significant increase in EF (28+/-12 to 41+/-18%, P=0.01) and a trend to greater LV FS (20+/-10 to 38+/-17%, P=0.06). Post-dialysis ECFV was not affected by dialysis mode (18.5+/-5.1 vs 18.2+/-3.5 l, P=0.76). The number of prescribed cardiovascular medications was reduced (2.2-0.7, P=0.02). CONCLUSIONS: In ESRD patients with systolic dysfunction, NHD leads to a sustained increase of EF and a reduction in the requirement for vasoactive medications in the absence of any reduction in post-dialysis ECFV.     

Isoflurane and intravenous anesthesia used for induction before coronary artery bypass grafting

Induction of anesthesia with isoflurane in combination with fentanyl, thiopentone, nitrous oxide and pancuronium was studied in nine patients scheduled for coronary artery bypass grafting. Ejection fraction (EF) of the left ventricle was monitored with a single crystal probe linked to a microcomputer, after injection of 200 MBq Tc 99m-HSA. Stroke volume index determined by thermodilution and EF were used to calculate left ventricular end-diastolic volume index (LVEDVI). The degree of ischemia was numerically scored as evaluated from the ECG (modified V5 lead). The study protocol covered seven periods from awake before induction to 5 min after intubation. EF decreased moderately during intubation (P less than 0.05). Systemic vascular resistance index (SVRI) was decreased (P less than 0.05) at all times except during intubation when it was unchanged compared to control. LVEDVI decreased during induction (P less than 0.05), while left ventricular filing pressure remained unchanged. Heart rate did not change. Systolic arterial pressure decreased from 147 mmHg (19.6 kPa) to about 100 mmHg (13.3 kPa) during induction (P less than 0.05). Two patients were given vasoconstrictors because of low arterial pressure. The mean ischemic score did not change. One patient, however, had signs of progressive ischemia. In this patient isoflurane administration was stopped after the last recording and the ECG normalized within 20 min.     

慢性肾衰竭患者经皮冠状动脉介入治疗后血管并发症的临床研究

探讨慢性肾衰竭(CRF)合并冠心病患者经皮冠状动脉介入治疗(PCI)后穿刺部位血管并发症的影响因素.方法 在2 977例接受PCI治疗的冠心病患者中,其中CRF患者53例,肾功能正常患者2924例,比较2组穿刺部位血管并发症的发生率.在CRF患者中,按有、无穿刺部位血管并发症分为2组,比较2组性别、年龄、体质量指数、穿...     

Sleeve gastrectomy in obese Wistar rats improves diastolic function and promotes cardiac recovery independent of weight loss

BackgroundHeart failure with preserved ejection fraction is the most common cause of heart failure and is characterized by impaired diastolic relaxation. Bariatric surgery significantly improves diastolic relaxation, but a mechanism beyond weight loss remains unknown.ObjectivesWe tested the hypothesis that a sleeve gastrectomy (SG) will improve diastolic dysfunction independent of weight loss due to postoperative alterations in the enterocardiac axis.SettingUniversity research laboratory.MethodsMale Wistar rats were fed a high-fat diet (HFD) or low-fat diet (LFD) for 10 weeks and then divided into SG-HFD, pair-fed sham HFD, ad-lib sham HFD, or ad-lib sham LFD groups (n = 9–14 per group). At least 2 months postoperatively, cardiac function, meal tolerance, glucose tolerance, and cardiac gene expression were compared between groups.ResultsOnly the SG cohort showed significant improvements in postoperative diastolic relaxation (isovolumetric relaxation time pre-SG: 14.7 ± 2.3 msec, post-SG: 11.2 ± 1.8 msec, P < .001). SG significantly increased active glucagon-like peptide-1 (P = .03). Compared to pair-fed sham HFD rats, SG-HFD rats had significantly altered mRNA cardiac gene expression, including sarco/endoplasmic reticulum Ca2+-ATPase 2 a (SERCA2 a) (P < .001).ConclusionsSG improves diastolic function independent of weight loss in a rat model of obesity with beneficial alterations in cardiac gene expression of multiple known targets related to cardiac failure, including SERCA2 a. These data support that a greater curve gastrectomy induces beneficial intracellular cardiac signaling for diastolic function mediated by the enterocardiac axis that is independent of weight loss. These findings could translate to offering metabolic surgery to patients with heart failure with preserved ejection fraction.     

冠心病心力衰竭病人胸段硬膜外阻滞后心功能变化

目的：观察冠心病心力衰竭（CHF）病人高位胸段硬膜外阻滞（HTEA）前后脂质过氧化物和左心室舒缩功能的变化，方法：选择48例冠心病心力衰竭病人均分为HTEA组（n=24)及常规治疗组（n=24),观察治疗前后心功能，丙二醛（MDA），超氧化物歧化酶（SOD）的变化。结果：治疗后CHF病人心脏舒缩功能的改善；HTEA组明显优于常规治疗组（P＜0．05），MDA含量HTEA组明显低于常规治疗组（P＜0．01），SOD则明显高于常规治疗组（P＜0．05），结论：HTEA治疗CHF病人对心脏舒缩功能的改善明显优于常规法，其增强抵抗自由基的能力是可能的机制之一。