Starting dose and dose adjustment of non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation.

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in "non-valvular atrial fibrillation" (NVAF). METHODS: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with "NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. RESULTS: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. CONCLUSIONS: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.

Perioperative dental screening and treatment in patients undergoing cardiothoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, a systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients, had never been defined. Following the systematic review, several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently, and then, a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus will become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Perioperative dental screening and treatment in patients undergoing cardio-thoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections, and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients had never been defined. Following the systematic review several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently and then a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions, and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus can become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

The worrisome liaison between left ventricular systolic dysfunction and mitral annulus calcification in type 2 diabetes without coronary artery disease: data from the SHORTWAVE study.

BACKGROUND AND AIM: Mitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function. METHODS AND RESULTS: As many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S') were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). Patients who had MAC (107 = 28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4 ± 14.9 vs 92.6 ± 14.3%; p = 0.01) and peak S' (8.9 ± 2.2 vs 10.0 ± 2.0 cm/s; p < 0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors associated with MAC. CONCLUSIONS: MAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV.

Hospitalization rate as a proxy for the quality of life evaluation: the case of dilated cardiomiopathy.

RATIONALE, AIMS AND OBJECTIVES: Some objective indicators like symptoms, toxicity, performance status, rate of hospitalization or re-employment have been already employed in scientific literature as proxies of Quality of Life assessment, and, in spite of the intrinsic limitations of such a measurement, they represent a valuable source of information in all the situations where a formal assessment is impossible, due to budget, time or human resources constrains. We concentrate here on some models for the analysis of frequency of hospitalization data and we discuss an application to the Hearth Muscle Disease Study Group data. METHODS: A sample of 235 patients with dilated cardiomyopathy (DCM) prospectively treated at the Department of Cardiology (Trieste, Italy) have been observed during a period of 18 years, from 1978 to 1992 and data regarding hospitalization history were collected. The hospitalization process depends on the time since the last event, and usually is a function of a set of explanatory variables, such as the current state of the patient, treatments he has been receiving and the severity of disease. We propose here a semi-Markov representation of the hospitalization process, and we analyze data regarding DCM, implementing Exponential, Weibull, and Cox models; in Cox models we take care also of the stratification according to the duration or to the levels of the state factor. RESULTS: The probability of experiencing a second hospitalization within one year after the first one is estimated about 0.50, and within two years about 0.30. After this point the probability remains constant at a 0.10 level. The same pattern is observed for the second hospitalization, while things are getting worse after the third hospitalization, when the probability of not having a subsequent hospitalization is about 0.10 within one year. Betablockers have a strong influence in enlarging the time interval spent between an hospitalization and the other. CONCLUSIONS: The hospitalization process can be viewed only as a rough approximation of the good standing of the patient. However, for diseases like DCM can be reasonable, because of the relatively fast increment in the worsening conditions of the patients and the consequently high chances of observing new hospitalizations up to the absorbing state (the death). Moreover a very detailed modeling of the process leads to extract as much information as possible from the data.

[Temporal trends in pharmacological therapy in the IN-CHF registry from 1995 to 2005]. / Come è cambiata la terapia farmacologica nel registro IN-CHF dal 1995 al 2005.

In the last years the treatment of heart failure has radically changed due to the results of multicenter clinical trials. The antagonism of neurohormonal systems has proved to be the only strategy, which favorably modifies the prognosis of the patients with heart failure. Particularly, the effectiveness of angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers has been proven in patients with heart failure and left ventricular dysfunction; more recently, angiotensin receptor blockers (ARBs) and aldosterone blockers have shown to improve the outcome in heart failure. The public health im portance of translating this body of evidence of research into clinical practice is paramount. We used data from the IN-CHF registry to examine changes in the use of pharmacological treatment from 1995 to 2005. The proportion of patients receiving an ACE-inhibitor was slightly higher in the 1995-2000 than after but this difference is not statistically significant. The use of "recommended therapies" as beta-blockers, aldosterone antagonists and ARBs increased significantly in these 10 years. The use of beta-blockers also increased significantly among elderly patients and patients in advanced NYHA class. Patients treated with the combination of ACE-inhibitors and ARBs are very few (1.1%), even if this association is now recommended by the European Society of Cardiology guidelines. The same analysis repeated after the CHARM and Val-HeFT publication shows that this association is used in 2.0% of the patients. The proportion of patients treated with a beta-blocker plus ACE-inhibitors plus ARB is only 0.8%. Use of digitalis and calcium channel blockers fell continuously from 1995 whereas use of diuretics and anticoagulants remained relatively constant. Statins are becoming widely used in this population (from 5 to 20%) even if the information on the effect of these drugs in heart failure is still incomplete.

The 'real' woman with heart failure. Impact of sex on current in-hospital management of heart failure by cardiologists and internists.

AIM: To identify differences between sexes in the clinical profile, use of resources, management and outcome in a large population of 'real world' patients with heart failure (HF). METHODS: A prospective cross-sectional survey was conducted on 2127 consecutive patients (47% women) admitted with HF to 167 cardiology and 250 internal medicine departments between February 14 and 25, 2000. RESULTS: Women were older, had a higher prevalence of atrial fibrillation, and more frequently a hypertensive or valvular aetiology. Females were admitted more frequently in Medical than in Cardiology Departments. The rate of invasive and non-invasive procedures was lower in women than in men, slightly higher if managed by cardiologists. Women were less frequently prescribed ACE-inhibitors, amiodarone, and spironolactone, and more frequently prescribed digoxin. In-hospital mortality was similar, without difference between health-care providers. A 6-month follow-up was performed in 56.4% of the cases in both setting, but less frequently in women. Event rates were similar with nearly half of patients re-hospitalised at least once. CONCLUSION: The 'real' HF woman has generally a more severe disease; she is an old lady who is more frequently hospitalised in a medical unit, receives few diagnostic, and cardiovascular procedures and pharmacological therapy, has a relatively low probability of dying in hospital, but a high likelihood of requiring readmission.

Long-term monitoring of sleep apnea at home in heart failure patients: preliminary results from the HHH study.

Sleep apnea is very common in patients with chronic heart failure (CHF) and has important implications in terms of morbidity, mortality and clinical management. Home respiratory telemonitoring might constitute a potential low-cost, widely-applicable alternative to traditional polysomnography in the evaluation and long-term monitoring of breathing disorders in these patients. In this paper we briefly describe the technological infrastructure and present preliminary results of the European Community multicountry trial HHH (Home or Hospital in Heart Failure), which is currently testing a novel system for home telemonitoring of cardiorespiratory signals in CHF patients. The recording and transmitting devices are suitable to be self-managed by the patient. We give a detailed report on the prevalence of nocturnal respiratory disorders at the beginning of the one-year follow-up and on their persistency over the following recordings (one per month). These preliminary findings clearly indicate that intermittent home telemonitoring of respiratory signals based on patient's self-management is feasible in CHF patients and the compliance is high. Reported statistics unambiguously confirm the high prevalence of nocturnal breathing disorders in these patients and clearly show that this phenomenon tends to persist over time.

[Integrated models between hospital and field for patients with heart failure]. / Modelli integrati tra ospedale e territorio per l'assistenza al paziente con scompenso cardiaco.

Chronic heart failure is a major health problem, which is growing parallel to the increasing proportion of elderly in the population. Recurrent hospitalizations occur in about half of the subjects within 6 months after the initial admission. Several co-morbidities usually coexist in these patients and influence resource utilization and outcome. The high re-admission rates and low proportion of patients who are currently enrolled in specific follow-up programs underscore the existing pitfalls in outpatient care, and the lack of co-operation between hospital departments and out-of-hospital clinics or general practitioners. As a consequence, up to half of the hospital admissions may be caused by potentially preventable factors. As worldwide health-care cost-containment escalates, it becomes crucial to develop new cost-effective strategies to improve the quality of care of more severe patients. The implementation of clinic-based heart failure programs showed some evidence of an improvement in functional status and in the frequency of hospital readmissions. However, patients referred to Heart Failure Clinics represent a selected population of patients compared to the overall population of "real-world" elderly patients with incapacitating symptoms, serious co-morbidities and frequent inability to attend an outpatient clinic. Few trials are currently available to verify the efficacy of a clinic-based approach in such patients, with discordant results. Other studies have extended the multidisciplinary program to the patient's home. These strategies might be particularly appropriate and cost-effective if targeted to elderly and higher-risk patients, and appear to be of particular relevance given the phenomenon of progressive aging of the general population. The results of our intensive, nurse-monitored, homecare surveillance on quality of life and hospitalization rate in elderly patients with refractory heart failure who previously failed to reach the goal of clinical stability with a clinic-based program extend the effectiveness of heart failure programs, in terms of quality of life and hospital readmission, to terminally ill subjects with short life expectancy and very high resource utilization.

Benefits of beta-blockers in heart failure: a class specific effect?

There is now compelling evidence in favor of the use of beta-adrenergic antagonists for the treatment of chronic heart failure. In clinically stable patients who remain symptomatic despite the fact that they are already receiving an angiotensin-converting enzyme inhibitor, diuretics and digoxin, the addition of a beta-blocker has been shown to produce further improvements in cardiac function and structure as well as in the quality and quantity of life. However, although such benefits can be achieved with a number of beta-blockers, the relevant differences in the ability of inhibiting the adrenergic drive among the various agents in the same class could translate into quantitatively different clinical effects. At present, the question whether all beta-blockers confer equal benefit or not to heart failure patients remains unanswered, since only few studies have prospectively addressed the issue and overall evidence does not permit to draw a conclusion that one agent has to be preferred to another. A large ongoing trial, designed to compare the effects of metoprolol and carvedilol on all-cause mortality in chronic heart failure, will provide much of the information required.

Current perspective new insights into the molecular basis of familial dilated cardiomyopathy.

Genetic disease transmission has been identified in a significant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, as well as recent molecular genetic data, indicate the existence of several genes causing the disease. Several distinct subtypes of familial DCM have been identified. Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene. This latter gene has recently been found to be responsible for both the autosomal dominant form of DCM with subclinical skeletal muscle disease (7.7% of cases) and the familial form with conduction defects (2.6% of cases) or the autosomal dominant variant of Emery-Dreifuss muscular dystrophy. The autosomal recessive form of DCM accounts for 16% of cases and is characterized by a worse prognosis. An X-linked form of DCM (10% of cases) manifests in the adult population and is due to mutations in the dystrophin gene. In the rare infantile form of DCM, mutations in the G4.5 gene have been identified. Finally, some of the rare unclassifiable forms (7.7% of cases) may be due to mitochondrial DNA mutations. Clinical and experimental evidence based on animal models suggest that, in a large number of cases, DCMs are diseases of the cytoskeleton. However, other causes, such as alterations in regulatory elements and in signaling molecules, are possible. Moreover, other genes called modifier genes can influence the severity, penetrance, and expression of the disease, and they will be a main objective of future investigations. Familial DCM is frequent, cannot be predicted on a clinical or morphological basis and requires family screening for identification. The advances in the genetics of familial DCM can allow improved diagnosis, prevention and genetic counseling, and represent the basis for the development of new therapies.

[Changes in medical treatment of heart failure in the light of large clinical trials]. / Come è cambiata la terapia medica dello scompenso cardiaco alla luce dei grandi trial clinici.

In the last years, the treatment of heart failure has radically changed, as has knowledge of this complex and heterogeneous clinical syndrome. This is largely due to the results of several multicenter clinical trials, which have been undertaken since the late 80's. These trials have not only contributed to the elaboration of present-day treatment protocols, but also to a better understanding of the pathophysiologic mechanisms involved in heart failure. In the past, heart failure was generally interpreted on the basis of pathophysiologic models according to which hemodynamic abnormalities played a very important role in determining the clinical presentation and evolution of the disease. This led to the use of digitalis, diuretics, inotropic drugs and vasodilators for the treatment of heart failure. More recently, improved knowledge of the pathophysiologic mechanisms involved in the progression of this disease has highlighted the central role and the complexity of various neurohormonal mechanisms. Antagonism of these systems has proved to be the only strategy which favorably modifies the natural history of heart failure. The proved effectiveness of ACE-inhibitors and particularly of beta-blockers in patients with heart failure and left ventricular systolic dysfunction was the most convincing demonstration of the validity of this model. However, the evolution and updating of the guidelines on the treatment of heart failure should only be considered as the first step in the development of strategies aimed at extending these principles to daily clinical practice and in particular to the real patient who is different from patients typically enrolled in heart failure trials. Moreover, the development of new effective models for the management of the ever-growing number of patients with heart failure is of utmost urgency.

Metoprolol-induced functional benefit in dilated cardiomyopathy is sustained over four years and favorably influences outcome.

BACKGROUND: Beta-blockers improve survival and ventricular function in patients with heart failure. We evaluated the long-term persistence of metoprolol-induced improvement and its impact on prognosis in idiopathic dilated cardiomyopathy. METHODS: Two hundred and four of 586 patients enrolled in a registry on the natural history of idiopathic dilated cardiomyopathy survived 4 years without transplantation; 98 of them were on standard heart failure treatment, whereas 106 took metoprolol in addition. We analyzed the effects of treatment using beta-blockers in terms of changes in left ventricular ejection fraction (LVEF), NYHA functional class and left ventricular end-diastolic diameter index (LVEDDI) after 1, 2 and 4 follow-up years in order to elaborate an improvement score that was related to the subsequent outcome over 60 months after the 4-year follow-up visit. RESULTS: Greater LVEF increases and NYHA functional class and LVEDDI decreases were observed in patients submitted to metoprolol vs standard treatment at all stages of follow-up. Changes (delta vs baseline) for LVEF (p = 0.02), NYHA functional class (p = 0.0001) and LVEDDI (p = 0.004) were maximal during the first year (10 +/- 11 vs 6 +/- 12 units, -0.72 +/- 0.77 vs -0.23 +/- 0.81, -3.5 +/- 5 vs -1.6 +/- 3.5 mm), persisted at 2 (12 +/- 12 vs 8 +/- 12 units, -0.80 +/- 0.70 vs -0.37 +/- 0.87, -4.2 +/- 5 vs -2.3 +/- 4 mm) but showed a trend to decline at 4 years (11 +/- 12 vs 8 +/- 13 units, -0.54 +/- 0.90 vs -0.24 +/- 0.91, -4.3 +/- 5 vs -2.3 +/- 5 mm) of follow-up. Improvement at 4 years was associated with a better transplant-free survival (81 vs 52%, p = 0.0005, odds ratio 0.36, 95% confidence interval 0.18 to 0.74). CONCLUSIONS: In idiopathic dilated cardiomyopathy, the more significant improvement in symptoms and left ventricular function and size, that is observed following treatment using metoprolol, translates into a better outcome. These benefits peak within the first 2 years of start of treatment but may begin to fade thereafter.

[Echocardiographic follow-up of patients with heart failure. Which parameters should be measured? How often?]. / Il follow-up ecocardiografico del paziente con scompenso cardiaco. Quali parametri misurare? Con quale frequenza?

The echocardiographic evaluation keeps a relevant place in the evaluation of patients with heart failure and left ventricular systolic dysfunction, not only for its contribution to the diagnosis, prognostic stratification and comprehension of pathogenetic mechanisms, but also for the analysis of the evolution of the disease and the response to optimal medical therapy. On the other hand, the role of echocardiography in the follow-up of patients with diastolic dysfunction is still unclear. In patients with heart failure and left ventricular systolic dysfunction the analysis of changes in left ventricular function and dimension during follow-up is particularly relevant to recognize the potential benefit of optimal medical therapy with ACE-inhibitors and beta-blockers and their prognostic significance. The echo-Doppler hemodynamic evaluation is also of clinical and prognostic value particularly for the recognition of the persistence or (re)appearance of restrictive filling pattern during follow-up. Moreover, in patients with persistent severe left ventricular systolic dysfunction, the evaluation of right ventricular function may allow for the identification of a subset of patients at high risk for cardiovascular events. A practical flow-chart of echocardiographic assessment of patients with heart failure and left ventricular systolic dysfunction includes the following steps: 1) after 3 to 6 months on optimal therapy, to detect the persistence of restrictive filling pattern, if present at diagnosis; 2) after 12 to 24 months, to analyze the response of left ventricular function and dimension to optimal medical treatment; 3) serial examinations, according to the stage of the disease or to the episodes of worsening heart failure, to identify echocardiographic indicators of disease progression, such as worsening of left ventricular and/or right ventricular function or (re)appearance of restrictive filling pattern. The changes in these parameters seem to have a relevant prognostic significance to define the risk profile of patients with heart failure and left ventricular systolic dysfunction.

[Heart failure due to diastolic dysfunction: the treatment principles]. / Scompenso cardiaco da disfunzione diastolica: principi di trattamento.

The clinical relevance of diastolic dysfunction in heart failure has recently been emphasized. In fact, the presence of signs of heart failure does not imply a depressed left ventricular systolic function; moreover, the severity of heart failure and effort tolerance are more closely related to diastolic than to systolic indexes. However, the principal trials about the treatment of heart failure were mainly addressed to patients with significant left ventricular systolic dysfunction, whereas the optimal therapy for diastolic dysfunction is not well known. The aim of this review was to assess the rationale and the therapeutic options in heart failure due to diastolic dysfunction. A diastolic dysfunction can be exclusive or associated with systolic dysfunction, as in dilated cardiomyopathy. It has to be noted that in this disease an improvement of diastolic function was demonstrated for most of the drugs currently employed in the treatment of heart failure, such as vasodilators, ACE inhibitors, beta-blockers, digitalis, and other inotropic drugs. Moreover, the favorable effect of the treatment on diastolic parameters (reduction of left ventricular filling pressure, regression of restrictive filling pattern) is associated with a positive prognostic impact. The main objective of the treatment of heart failure with preserved left ventricular systolic function is to control the symptoms by means of lowering high left ventricular filling pressure without significantly lowering cardiac output. According to the therapeutic guidelines of the American College of Cardiology/American Heart Association Task Force, the drugs indicated to treat symptomatic patients with heart failure and preserved left ventricular systolic function are diuretics and nitrates. Potentially useful, but with insufficiently proven efficacy are beta-blockers, calcium antagonists and ACE inhibitors, whereas direct vasodilators and inotropic drugs were considered inadvisable. It is important to remember that the treatment might possibly be oriented to the cause and also to the possible precipitating factors of the heart failure syndrome (i.e. ischemia, tachycardia, arrhythmias, hypertension). In conclusion, considering the relatively common incidence of heart failure due to prevalent diastolic dysfunction, and the few available data about the therapeutic options in these patients, large multicenter trials devoted to the treatment of this syndrome are needed.