Chronic heart failure (CHF) is a complex group of clinical symptoms, the end stage of various heart diseases, with high morbidity and mortality. According to statistics, the prevalence of CHF in the general population is about 1.0% to 2.0%, and up to 6% to 10% in people over 65 years old. The results of a random sample survey of a total of 15518 urban and rural residents aged 35-74 in China: the prevalence of heart failure is 0.9%, and there are about 4 million heart failure patients, of whom 0.7% are men and 1.0% are women, with women being higher than men. With the aging of the population, its prevalence is on the rise. in patients over 65 years of age, CHF is the leading cause of hospitalization. For this reason, the treatment of CHF will be a top priority for every cardiovascular physician. Of course, the treatment of heart failure is supposed to vary according to its underlying disease. Currently, there are pharmacological and non-pharmacological treatments for heart failure. Non-pharmacological treatments such as minimally invasive interventions, stem cell therapy, biventricular synchronization therapy (CRT) and gene therapy have developed rapidly in recent years, but there are still some controversies. Due to economic problems, they are not yet accepted by the majority of patients. Therefore, drug therapy is still the main means of heart failure treatment at present. Wei Feng, Department of Cardiology, Bengbu First People’s Hospital
The treatment of chronic heart failure (CHF) has shifted from short-term hemodynamic/pharmacological measures before the 1990s to a long-term, restorative strategy that aims to change the biological properties of the failing heart. The goal of heart failure treatment is not only to improve the patient’s symptoms and quality of life, but more importantly to target the mechanism of heart failure, myocardial remodeling, to prevent and delay its progression and thus reduce mortality and rehospitalization rates in heart failure. I. Removal of predisposing factors
For example: infection, pulmonary infarction, arrhythmia especially atrial fibrillation with rapid ventricular rate, electrolyte disorders and acid-base imbalance, anemia, renal impairment, etc., should be treated and corrected in time.
II. Weight monitoring
Do daily weight measurement for early detection of fluid retention. If the weight suddenly increases by more than 2 kg within 3 days, the patient should be considered to have sodium and water retention (occult edema) and the diuretic dose should be increased.
III. Lifestyle adjustment
1. Sodium restriction: Patients with heart failure have a significantly increased ability to retain sodium, so it is important to appropriately restrict sodium intake in the daily diet. Try to avoid finished foods. Sodium intake in 2-5 g/d, avoid salt-pickled food ①.
2. Water restriction: in severe hyponatremia (blood sodium <130 mmol/L), fluid intake should be <2 L/d.
3. Nutrition and diet: low-fat diet is recommended, obese patients should reduce weight and quit smoking.
4. Rest and moderate exercise: bed rest is required in the decompensated phase, and more passive exercise is needed to prevent deep vein thrombosis. After the clinical condition improves, physical activity should be encouraged without causing symptoms to prevent the “de-adaptation” of muscles.
IV. Psychological and psychiatric treatment
V. Drugs to be avoided
Non-steroidal anti-inflammatory drugs and COX-2 inhibitors. ②Corticosteroids. ③Class I antiarrhythmic drugs. ④Most CCBs, including diltiazem, verapamil, and short-acting dihydropyridine preparations. ⑤ “Myocardial nutrition” drugs, such as coenzyme Q10, taurine, etc., the efficacy of which is uncertain, and the treatment of heart failure drugs, there may be interactions between the use is not recommended.
VI. Oxygen therapy
I. Diuretics
Diuretics curb sodium retention in heart failure by inhibiting sodium or chloride reabsorption at specific sites in the renal tubules, reduce venous return and lower preload, thereby reducing pulmonary stasis, improving cardiac function and increasing exercise tolerance. The appropriate use of diuretics is one of the key factors in the success of other drugs used to treat heart failure and is an essential component of standard therapy. Clinically, the application of diuretics generally results in a rapid resolution of heart failure symptoms. It is worth mentioning that diuretics should not be used as monotherapy even when heart failure symptoms are controlled and clinical status is stable. Diuretics should generally be used in combination with ACEI and β-blockers and the earlier they are used, the better. The commonly used diuretics are loop diuretics and thiazides. According to the study of the mechanism of action of the two types of drugs combined with clinical application, loop diuretics are the first choice for most patients with heart failure, especially for patients with significant water and sodium retention or with impaired renal function. The representative drug, furosemide, has an unrestricted dose because of its linear relationship between dose and effect. According to the study, hydrochlorothiazide 100 mg/d has reached the maximum effect (dose-effect curve has reached the plateau), and further increase in dose is not effective. Usually start with small doses, such as furosemide 20-40 mg qd or hydrochlorothiazide 25-50 mg qd, or butalbital 1-2 mg qd for poor diuretic effect, or alternate between these two diuretics every two days. Once the disease is under control (pulmonary coarseВ purple juggling is debatableǎ hurriedly zai plutonium ∮ lineЪ bright cutて deceive frameT eulogizeて deceive pride Yeol miscellaneous Ω菀 Wo profound grudge po po that sachet griddle simply barium scalping bright finish . Another important class of diuretics, aldosterone receptor antagonists, also play an important role in the treatment of CHF. the RALES study showed a 30% reduction in the relative risk of death and a 35% reduction in heart failure hospitalizations in patients in NYHA class IV or III. the EPHESUS study showed that in patients with LVEF ≤ 40%, evidence of clinical heart failure or diabetes, and myocardial infarction within 14 days, the relative all-cause mortality rate at 1 year was less than 1.5%. The EPHESUS study showed a 15% reduction in the relative risk of all-cause mortality, a 21% reduction in sudden cardiac death, and a 13% reduction in cardiovascular mortality and hospitalization for heart failure at 1 year in patients with LVEF ≤ 40%, clinical evidence of heart failure or diabetes, and myocardial infarction within 14 days. Therefore, its representative drug, spironolactone (20-40 mg qd), has become an essential drug in the treatment of CHF. In addition to potassium preservation, it has antagonistic effects on cardiotoxicity and interstitial hyperplasia of the RAS system, and can act as a neuroendocrine antagonist to block ventricular remodeling and slow down the progression of heart failure. Long-term use of diuretics should be closely monitored for adverse effects such as electrolyte disturbances, symptomatic hypotension, and renal insufficiency, especially in high doses and in combination. The NSAID indomethacin inhibits the natriuretic effect of most diuretics, especially loop diuretics, and promotes the azotemic tendency of diuretics and should be avoided.Tolvaptan and Rolofylline are two diuretics currently under investigation.Tolvaptan is a vasopressin receptor antagonist that selectively blocks arginine vasopressin receptors on renal tubules The EVEREST study showed that with short-term application of Tolvaptan, shortness of breath and edema were significantly reduced in heart failure patients with increased volume load, and clinical symptoms were significantly better than in the control group. No reduction in mortality was seen with long-term treatment. Rolofylline is an adenosine receptor antagonist, and the PROTECT study on it is ongoing and will be completed in 2009, we will see.3
II. Angiotensin-converting enzyme inhibitors
ACEI is the first class of drugs proven to reduce mortality in patients with heart failure and is the drug with the most accumulated evidence in evidence-based medicine, and the US guidelines for the treatment of chronic heart failure consider ACEI as the basic drug for the treatment of heart failure regardless of the degree of CHF. The SOLVD prevention study, SAVE and TRACE trials also showed that asymptomatic patients with left ventricular insufficiency were less likely to develop symptomatic heart failure and be admitted to hospital due to worsening heart failure after ACEI. The basic principle of ACEI application is to start with a very small dose and gradually increase it until the target dose is reached, usually with a dose doubling every 1-2 weeks. The speed of dose adjustment depends on the clinical condition of each patient. Of course, based on the results of clinical trials, high doses may further reduce the rate of hospitalization for heart failure, but the benefits in terms of symptoms and mortality are similar to those of low and moderate doses. Slow increments are advisable in patients with a history of hypotension, diabetes mellitus, azotemia, etc. Once adjusted to an appropriate dose it should be maintained for life to reduce the risk of death or hospitalization. In patients with previous or current fluid retention, ACEI must be used in combination with a diuretic, and care should be taken to maintain the diuretic at the most appropriate dose before initiating therapy. ACEI is generally used in combination with beta-blockers because of their synergistic effect. ACEI has two adverse effects: (i) those related to Ang II inhibition, including hypotension, deterioration of renal function, and potassium retention; and (ii) those related to bradykinin accumulation, such as cough and angioedema. Clinical application should be aware of the occurrence of these adverse reactions. When applying ACEI, attention should be paid to the hypotensive reaction to the first dose of ACEI and the change of renal function.
β-blockers
Beta-blockers are strong negative inotropic agents and have previously been contraindicated in the treatment of heart failure. However, in mild heart failure, β-blockers are excellent therapeutic agents, and their effectiveness is equivalent to that of ACEI and ARB. most large-scale studies have confirmed their significance in the treatment of heart failure.4 According to a meta-analysis, 39 clinical trials applying ACEI (8308 heart failure, 1361 deaths) showed a 24% reduction in the risk of death, while β-blockers with ACEI resulted in a 36% reduction in the risk of death. Clinically, β-blockers should be used in patients with stable NYHA class II and III, asymptomatic heart failure or NYHA class I (LVEF <40%), and should be used for life unless contraindicated or intolerable. β-blockers can be used under specialist supervision in patients with stable NYHA class IV heart failure and under dry weight conditions. Usually beta-blockers improve heart failure symptoms after 2 to 3 months of treatment, so they should be used as early as possible in the application schedule. It is contraindicated in patients with combined bronchospastic disease, bradycardia (heart rate <60 beats/min), second degree type II or greater atrioventricular block (unless a pacemaker has been pressed into service), and cardiogenic shock. For patients with significant fluid retention in heart failure, dry weight needs to be achieved before starting the application.
The commonly used beta-blockers in clinical practice are metoprolol succinate, bisoprolol or carvedilol.
According to three large clinical trials, CIBIS-II, MERIT-HF and COPERNICUS, it is suggested that there is no difference between selective and non-selective β-blockers. Metoprololpine tartrate tablets have been used for the treatment of heart failure in China since the publication of the recommendations for the treatment of chronic systolic heart failure in 2002. The doses used generally start at very low doses, such as metoprolol succinate 12.5-25 mg once daily, bisoprolol 1.25 mg once daily, or carvedilol 3.125 mg twice daily. If the patient tolerates the previous dose, the dose is doubled every 2 to 4 weeks; if an adverse reaction occurs at the previous lower dose, the dose increase may be delayed until the adverse reaction resolves. The patient should increase the diuretic dosage once weight gain occurs during treatment until the pre-treatment weight is restored, and then continue to increase the dosage to the target dose. It is important to monitor for adverse reactions during treatment. For example, hypotension, fluid retention and worsening of heart failure, bradycardia (heart rate <55 beats/min) and atrioventricular block (2nd and 3rd degree AV block) and weakness. Reduce the dose or even stop the drug for observation if necessary.
Digoxin
The treatment of heart failure has long been attributed to the positive inotropic effect of digitalis, i.e., digitalis exerts a positive inotropic effect by inhibiting the Na+/K+-ATPase of the failing myocardial cell membrane, which increases the intracellular Na+ level, promotes Na+-Ca2+ exchange, and increases the intracellular Ca2+ level. Patients benefited from digoxin therapy regardless of whether the underlying rhythm was sinus or atrial fibrillation, ischemic or non-ischemic cardiomyopathy, or combined or uncomplicated use of ACEI; discontinuation of digoxin resulted in worsening of hemodynamics and clinical symptoms. However, long-term clinical observations and studies have found that digoxin can only improve clinical symptoms but not reduce mortality in patients with heart failure, so its early application is not recommended, nor is it recommended for patients with NYHA class I cardiac function.
Digoxin is the only positive inotropic drug that has been confirmed by the U.S. Food and Drug Administration (FDA) to be effective in treating CHF, and is most widely used clinically. The main adverse effects include cardiac arrhythmias, gastrointestinal symptoms and neuropsychiatric symptoms. Contrary to conventional wisdom, digoxin is safe and well tolerated. Adverse reactions are mainly seen at high doses, but high doses are not required for the treatment of heart failure and are observed with clinical attention.
Recently a new Na/K-ATPase inhibitor —–istaroxime has entered clinical trials. This agent enhances myocardial contractility by stimulating the influx of calcium ions through the posterior myocardial cytoplasmic membrane sodium-calcium ion exchanger. Preliminary animal studies have shown a broader and safer range of safety than digoxin. results of the HORIZON-HF study presented at ACC 2008 showed that istaroxime enhanced myocardial contraction and accelerated diastole, and enhanced the pumping function of the heart, without lowering blood pressure or accelerating heart rate in patients with acute heart failure syndrome (AHFS). It is believed that this drug will contribute to further control of heart failure symptoms in clinical practice in the near future.
V. Angiotensin II receptor antagonists
In clinical practice, we usually use ARB agents for replacement therapy for patients who cannot tolerate ACEI therapy. In the CHARM-substitution trial, over 2,000 heart failure patients who could not tolerate ACEI were treated with candesartan, and the results showed a 23% reduction in the primary endpoint of cardiovascular death or hospitalization for worsening heart failure, demonstrating the effectiveness of candesartan. The Val-HeFT trial showed that the addition of R sartan to ACEI reduced the combined endpoint of death and disability by 13% compared with placebo, and improved cardiac function class, LVEF and quality of life, with a reduction in mortality in the ACEI-free subgroup. In recent years, the accumulation and refinement of clinical observations of ARBs has led to an increase in the status of ARBs in the treatment of heart failure. They are usually started at small doses and gradually increased to the recommended dose or the maximum tolerated dose on the basis of patient tolerance. For example, the starting dose of candesartan is 4-8 mg/d, and the recommended dose is 32 mg/d; the starting dose of irbesartan is 150 mg/d, and the recommended dose is 300 mg/d, etc. The precautions for ARB application are similar to those for ACEI, and blood pressure, renal function and potassium should be monitored during the application.
Sixth, vasodilators
Vasodilators have been used in the treatment of heart failure for more than 20 years, and with the emergence of more and more multicenter randomized controlled large series of long-term clinical trials in recent years, clinicians have a deeper understanding of the role and efficacy of vasodilators in the treatment of heart failure. Commonly used in clinical practice are nitroglycerin, cardiac pain relief, sodium nitroprusside, phentolamine, nesiritide, ACEI and calcium channel blockers. Vasodilators improve heart failure symptoms by reducing ventricular pre and/or afterload, especially afterload, and by reducing mitral and tricuspid regurgitation, resulting in reduced ventricular volumes, reduced ventricular filling pressures and ventricular wall stresses and/or increased beat volumes while ensuring cerebral and cardiac perfusion pressures. Care should be taken when applying vasodilators, and they should be used with caution in patients with heart failure associated with hypotension and, if necessary, in combination with dobutamine.5 Calcium channel blockers are not recommended in the first 12 hours of acute heart failure, and sodium nitroprusside should not be used in acute heart failure associated with ACS because of its potential to cause coronary artery steal. As for nesiritide, several small clinical trials (VMAC,PRECEDENT,EFFICACY,COMPARATIVE) confirmed that nesiritide improved symptoms and hemodynamic status in acutely decompensated patients with CHF and significantly reduced the incidence of severe arrhythmias compared with dobutamine, but the effect on disability or mortality is not known. A large-scale clinical study to answer the safety and efficacy of nesiritide in patients with acute decompensated heart failure is in the pipeline.
VII. Combined application of neuroendocrine inhibitors
1. Combined application of ACEI and β-blockers: Clinical trials have confirmed that the two have synergistic effects and can further reduce mortality in patients with CHF. It should be emphasized that for patients with severe heart failure, they need to be stabilized for more than two weeks after cardiac, diuretic and ACEI treatment, and then add small doses of β-blockers on top of the original treatment, slowly increasing the dose to reach the therapeutic or tolerated amount after several weeks, and closely observe, and reduce or stop the dose if the heart failure is aggravated.
2, ACEI and aldosterone receptor antagonist combination: aldosterone receptor antagonist clinical trials are controlled with the standard treatment based on ACEI, confirmed that ACEI plus aldosterone receptor antagonist can further reduce the mortality of CHF patients.
3, ACEI plus ARB: The findings of the available clinical trials are inconsistent. The combination of valsartan and ACEI in the Val-HeFT trial did not reduce mortality. The combination of candesartan and ACEI in the CHARM combination trial reduced the primary endpoint of cardiovascular death or hospitalization for worsening heart failure by 15%. The benefit of combining valsartan with captopril in the VALIANT trial was not superior to either drug alone, while adverse effects were increased. The results of the ONTARGET study at the American College of Cardiovascular Disease (ACC) 2008 meeting gave a new perspective: ARB + ACEI, 1+1 is not greater than 2. Therefore, it is still debated whether ARB can be combined with ACEI to treat heart failure.
4, ACEI, ARB and aldosterone receptor antagonist combination: Although 17% of patients in the CHARM combination trial used spironolactone, experts agree that the safety evidence of ACEI, ARB and aldosterone receptor antagonist combination is not enough, and will certainly further increase the risk of abnormal renal function and hyperkalemia, so it can not be recommended.
5, ACEI, ARB and b-blockers combined: ELITE-2 and Val-HeFT trials have found that in patients already using ACEI and b-blockers, the addition of ARB increased mortality. However, subsequent OPTIMAL, VALIANT, and CHARM trials failed to replicate these findings. Therefore, there is no evidence that the combination of either ARB with b-blockers or ARB+ACEI with b-blockers is detrimental to patients with heart failure.
VIII. Anticoagulation and antiplatelet agents
The occurrence of stroke, pulmonary embolism and peripheral artery embolism in patients with heart failure is higher than that in the general population due to the stagnation of blood in the dilated and hypokinetic heart chambers, abnormal local ventricular wall motion, and increased activity of procoagulant factors, but antithrombotic therapy in heart failure patients has been controversial. Early reports on the prevalence of thromboembolism in China were mostly the result of autopsy studies, which were considered to be high, while retrospective analysis of clinical trials in heart failure showed that the rate of thromboembolism was not high, with an annual incidence of 1.5%-3.5%. Venous thromboembolism (VTE) is also an important cause of death in heart failure patients. chf is a clear risk factor for VTE. Several retrospective analyses (SOLVD, PROMISE, V-HeFT) have also not yielded a consistent opinion. A recently completed randomized controlled study of aspirin, warfarin, or clopidogrel in heart failure with low LVEF failed to conclude definitively whether heart failure is beneficial or to confirm which treatment is superior because the number of cases enrolled was too small.