Taboo in cardiology: renin-angiotensin-aldosterone system antagonists worsening renal failure.

The renin-angiotensin-aldosterone system (RAAS) allows normal kidneys to maintain a stable function in every situation of daily life but also intervenes to help when critical situations occur that reduce the filtrate. A typical example is heart failure with reduced ejection function (HFrEF) which inexorably becomes complicated over time with renal failure in what is now commonly defined as cardiorenal syndrome. Renin-angiotensin-aldosterone system antagonists have long been irreplaceable in the treatment of HFrEF due to their beneficial haemodynamic and prognostic effects. However, their use often leads to an acute reduction in the filtrate which often scares the clinician and sometimes leads them to suspend their use. In reality, no guideline has ever clearly indicated when a decline in renal function in a patient taking RAAS antagonists should be acceptable and not lead us to fear the associated acute kidney injury. Usually the nephrologist, called for advice, recommends reducing or suspending the RAAS antagonists, knowing that this will improve the filtration and reassure everyone. But is this the right solution? Are we certain that this choice leads to a better prognosis? This article will try to give a reasonable answer to one of the most frequent doubts that arise in our daily practice.

Coronary microvascular dysfunction affects left ventricular global longitudinal strain response to dipyridamole stress echocardiography: a pilot study.

The aim is to investigate, by means of speckle tracking echocardiography, left ventricular (LV) contractile function at rest and during dipyridamole stress in patients with coronary microvascular dysfunction (CMD). 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR < 2. Global longitudinal strain (GLS) was measured at rest and at peak dose. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (- 16.8 ± 2.7 vs. - 19.1 ± 3.1, p < 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from - 19.1 ± 3.1 to - 20.2 ± 3.1, p < 0.01), and significantly decreased in patients with CMD (from - 16.8 ± 2.7 to - 15.8 ± 2.7, p < 0.01). There was a significant inverse correlation between CFR and ∆GLS (r = - 0.82, p < 0.01). Rest GLS and GLS response to dipyridamole stress are markedly impaired among patients with chest pain syndrome, non-obstructive CAD and CMD, reflecting subclinical LV systolic dysfunction and lack of LV contractile reserve due to underlying myocardial ischemia.

Treating chronic kidney disease to reduce cardiovascular risk.

Chronic kidney disease (CKD) is a complex syndrome and a relevant problem of public health due to its large incidence and prevalence and to the high costs for its management. The hallmark of CKD, the progressive reduction in the glomerular filtration rate (eGFR), is strongly associated with an increase in cardiovascular events, such as fatal and non-fatal heart attack, stroke and heart failure, and mortality. Therefore, clinicians should pay any effort for preventing or slowing down the decline of renal function in order to reduce not only the occurrence of critical renal events (the need for dialysis or renal transplantation, among the most dreadful) but also the incidence of cardiovascular events. Accordingly, an early diagnosis and a targeted treatment in patients with kidney disease are crucial to reduce the evolution towards more advanced stages of the disease and the occurrence of complications. For a long time, the therapeutic approach to the majority of CKD patients was based on the strict control of risk factors, such as the diabetic disease and hypertension, together with the use of renin-angiotensin-aldosterone system inhibitors, particularly in the presence of albuminuria. Over time, this strategy proved to be only partially effective, since most CKD patients showed a progressive worsening of renal function. Gliflozins and incretins are novel anti-diabetic drugs that have been demonstrated to slow down the slope of eGFR reduction in patients with CKD, irrespective of diabetic status. Concurrently, these drugs showed to significantly impact cardiovascular prognosis reducing the incidence of clinical events. For their ability to act on a wide spectrum of disease, gliflozins and incretins are also called 'cardio-nephro-metabolic' drugs.

The implantable cardiac monitor in heart failure patient: a possible new indication?

Implantable cardiac monitors (ICMs) have found increasing use in clinical practice over the years, proving, when used in high-risk populations, to facilitate the diagnosis of bradyarrhythmias and tachyarrhythmias requiring treatment. Experience with heart failure patients undergoing pacemaker (PMK) or implantable defibrillator (ICD) implantation, which allow for continuous electrocardiographic monitoring and transthoracic impedance assessment, has made it possible to identify predictors of heart failure flare-ups. In this context, the use of telemonitoring has been shown to ensure better management of patients with heart failure. These benefits cannot be assessed to date in patients with heart failure and left ventricular ejection fraction (LVEF) > 35% who have no indication for PMK or ICD implantation. This population has been shown to have a significant incidence of ventricular arrhythmias and bradyarrhythmias. In addition, a significant number of cerebrovascular events are observed in this population, largely attributable to the high incidence of atrial fibrillation (AF). In this population, the occurrence of AF has also been shown to have a negative impact on patients' prognosis; at the same time, a rhythm control strategy has been shown to be more beneficial in this area than a rate control strategy. Studies also suggest arrhythmias have a negative impact on the cognitive status and quality of life of heart failure patients. These reasons could justify the implantation of ICMs equipped with telemonitoring systems in heart failure patients. The information provided by the monitoring system, if properly managed, could bring benefits in terms of prognosis and quality of life along with a reduction in economic costs. We will try here, by answering a few questions, to assess whether there is an indication for ICM in heart failure, which patients should be candidates and how these patients should be managed.

Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians.

The sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce risks of clinical events in patients with heart failure (HF), with early and sustained benefits regardless of ejection fraction, diabetic status, and care setting. As part and parcel of the modern foundational HF therapy, clinicians should be familiar with these drugs, in order to implement their use and limit the potential adverse effects. We present an up-to-date review of current evidence and a practical guide for the prescription of SGLT2 inhibitors in patients with HF, highlighting important elements for patient selection, treatment initiation, dosing, and problem solving.

Multimodality imaging in decompensated heart failure.

Heart failure (HF) is usually suspected by clinical history, symptoms, physical examination, electrocardiogram findings, and natriuretic peptides' values. However, echocardiography and other imaging techniques play an essential role in supporting HF diagnosis. Thanks to its non-invasiveness and safety, transthoracic echocardiography is the first-level technique of choice to assess myocardial structure and function, trying to establish the diagnosis of HF with reduced, mildly reduced, and preserved ejection fraction. The role of echocardiography is not limited to diagnosis but it represents a crucial tool in guiding therapeutic decision-making and monitoring response to therapy. Over the last decades, several technological advancements were made in the imaging field, aiming at better understanding the morphofunctional abnormalities occurring in cardiovascular diseases. The purpose of this review article is to summarize the incremental role of imaging techniques (in particular cardiac magnetic resonance and myocardial scintigraphy) in HF, highlighting their essential applications to HF diagnosis and management.

Sodium-glucose co-transporter 2 inhibitors for the treatment of cardio-renal syndrome.

The 2021 guidelines of the European Society of Cardiology on the diagnosis and therapy of heart failure (HF) introduced relevant changes in the pharmacological treatment of chronic HF. Among these, certainly the most significant was the introduction in the therapeutic flow-chart (with the highest recommendation level) of the sodium glucose co-transporter 2 (SGLT2) inhibitors. In fact, SGLT2 inhibitors are responsible for major paradigm shifts in the care of patients with or at high risk for HF, progression of chronic kidney disease, or both. SGLT2 inhibition demonstrated to improve cardiovascular outcomes in patients with HF over a wide range of ejection fractions, regardless of diabetic status, and have a strong nephroprotective effect. There are several important interactions between heart disease and kidneys disease. Indeed, acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. The term 'cardiorenal syndrome' has been applied to these interactions. Since kidneys dysfunction in the setting of HF has a strong prognostic relevance, drugs that can slow down the decline of renal function are of utmost importance. Here, we discuss about the beneficial effects of SGLT2 inhibitors on the kidneys function in patients with HF and how these effects can improve both renal and cardiovascular outcomes.

The uraemic hypertensive patient: a therapeutic challenge-right you are (if you think so).

High blood pressure (BP) is a leading cause of chronic kidney disease (CKD) and at the same time represents its most frequent complication. High BP is an independent risk factor for advanced CKD; on the other hand, at least 40% of patients with normal glomerular filtration rate (GFR) and virtually all patients with GFR <30 mL/min are hypertensive. CKD and microalbuminuria are powerful risk factors for cardiovascular morbidity and mortality. Consequently, in uraemic hypertension, it is of utmost importance to carefully manage both high BP and microalbuminuria, in order to slow down the progression of kidney damage and to reduce the incidence of cardiovascular events. The first purpose of the medical treatment in hypertensive patients is to normalize BP, regardless of the drug used. Nevertheless, some drugs have an 'additional' nephroprotective effect at the same BP target achieved. In this regard, first-line drugs are definitely renin-angiotensin-aldosterone inhibitors, mainly for their proved efficacy in reducing hypertension-related kidney damage and proteinuria. Anyway, a combined approach (two or more drugs) is usually needed to achieve the optimal BP target and reduce the worsening of CKD.

Renal insufficiency in acute heart failure: old habits we need to let go?

Heart failure and renal insufficiency often coexist in the same patient. Customarily, this condition is described as 'cardio-renal syndrome'. In this situation mortality increases significantly as the renal dysfunction worsen. Treating these patients is challenging, due to their instability (congestion needs to be controlled, while maintaining, or not worsening, organ perfusion), making in-hospital and mid-term mortality hard to improve. Congestion represent the key characteristic of this syndrome, and its treatment is far from been standardized, considering that the condition represent, still, the first cause of re-hospitalization for these patients. Present treatment should be modified, because barely accounts for renal physiology and is responsible for 'resistance to diuretics', which eventually becomes iatrogenic, and non 'sodium-dependent' hyponatraemia. It is then important to emphasize the importance of the 'sequential nephron blockade', to decrease the number of 'non-responder' to diuretics, and the possible role of the 'acquaretics'.

New Ultrasound Technologies for Ischemic Heart Disease Assessment and Monitoring in Cardiac Rehabilitation.

Owing to its ease of application, noninvasive nature, and safety, echocardiography is an essential imaging modality to assess cardiac function in patients affected by ischemic heart disease (IHD). Over the past few decades, we have witnessed a continuous series of evolutions in the ultrasound field that have led to the introduction of innovative echocardiographic modalities which allowed to better understand the morphofunctional abnormalities occurring in cardiovascular diseases. This article offers an overview of some of the newest echocardiographic modalities and their promising application in IHD diagnosis, risk stratification, management, and monitoring after cardiac rehabilitation.

Heart rate as independent prognostic factor for mortality in normotensive hemodialysed patients.

BACKGROUND: Several epidemiological studies have reported heart rate (HR) as a predictor of cardiovascular and noncardiovascular mortality in the general population. Aim of the present study was to investigate a possible relation between increased HR and mortality in normotensive end-stage renal disease (ERSD) patients. METHODS: Between 1997 and 2001 we recruited 407 normotensive ESRD patients (mean age 56.6 +/- 3.3 years) without coronary artery disease, left ventricular systolic dysfunction or on antiarrhythmic therapy. Baseline electrocardiography (ECG) at rest, 48-hour ambulatory Holter ECG monitoring and standard echocardiography were performed. After a mean follow-up of 46 months (range 12-60 months), cardiovascular and sudden death were considered as end points. RESULTS: Echocardiogram showed a normal left ventricular ejection fraction (>55%) in 370 patients (91%) and left ventricular hypertrophy (LVH) in 290 patients (71.2%). Mean HR by 48-hour Holter ECG was 81 +/- 10.6 bpm. During the follow-up, all-cause mortality rate was 12% (49 patients); 40 patients died from cardiac cause (9.8%) of which 20 patients (4.9%) by sudden death. By univariate analysis, age, diabetes, ECG-LVH with signs of left ventricular strain, and increased mean HR by 48-hour Holter ECG were all significantly related to global, cardiovascular and sudden death. ROC curve analysis identified optimal cutoff points for HR >85 bpm and age >65 years associated with increased cardiovascular risk (p<0.001). By Cox regression analysis, only age >65 years (p<0.0001) and mean HR >85 bpm (p<0.0001) were independent predictors of cardiovascular events. CONCLUSIONS: In normotensive ERSD patients, increased mean HR detected by 48-hour Holter ECG is an independent determinant of global and cardiovascular mortality.

Parathyroidectomy improves the quality of sleep in maintenance hemodialysis patients with severe hyperparathyroidism.

Sleeping disorders are very common in patients with chronic kidney disease on dialysis (CKD5D) and are an emerging risk factor able to predict mortality. Parathyroid hormone (PTH) although considered a pivotal uremic toxin has rarely been associated with sleep disorders in uremia. In a study from our laboratory PTH concentrations failed to distinguish patients with sleep disorders from those without. In a study performed by Chou et al a 97% prevalence of insomnia was found in patients undergoing hemodialysis requiring parathyroidectomy. Surgery reduced PTH and increased sleeping hours within 3 months. The aim of this study was to study the effects of parathyroidectomy on the sleep disorders of insomniacs on maintenance hemodialysis. The study was performed in 16 insomniac patients on maintenance hemodialysis who successfully underwent surgery with autotransplantation of autologous parathyroid tissue (40 mg) under the skin of the forearm. Patients (5 F and 11 M) were studied from 1 month before surgery to 1 year after. Sleep disorders were assessed by means of a 27-item questionnaire--Sleep Disorder questionnaire (SDQ)--that identified sleeping disorders according to Diagnostic and Statistical Manual of Mental Disorders - IV Edition (DSM-IV) criteria. The Charlson Comorbidity Index (CCI) was also measured along with systolic and diastolic blood pressure, Hb, PTH, Ca, P. A 95.5% prevalence of sleep disorders was found pre operatively. Patients slept 4.90+/-1.2 hours, Ca averaged 10.09+/-0.54 mg/dL, Phosphate 5.5+/-1.93, CCI 9.8+/-1.1, PTH 1498+/-498 ng/mL. After 1 year follow-up 2 out 16 patients had normal sleep, 6 out 16 patients had subclinical sleep disorders and 8 remained insomniacs (p=0.008, Mc Nemar Test for paired data, insomniacs vs. no disturbance + subclinical disorders). Sleeping hours increased up to 6.0+/-1.24 (p<0.05), PTH was normalized, the Charlson Comorbidity Index was reduced (p<0.05) as were plasma calcium and phosphate (p<0.01). The study indicates that insomnia in patients with severe hyperparathyroidism on maintenance hemodialysis is ameliorated by parathyroidectomy.

High prevalence of sleep disorders in hemodialyzed patients requiring parathyroidectomy.

OBJECTIVE: Although there has been contrasting evidence for a causative role of parathyroid hormone (PTH) in sleep disorders in patients on maintenance hemodialysis, a recent study disclosed the possibility that this role might exist at least in patients requiring parathyroidectomy because of failure of medical therapy. The present study was devised to assess a possible difference in sleep disorders of patients on hemodialysis needing parathyroidectomy and those in whom medical therapy controlled hyperparathyroidism. DESIGN AND PATIENTS: To this end, a group of 22 patients requiring parathyroidectomy were studied by means of a sleep questionnaire, along with a group of 44 patients matched for age, gender, body weight, and duration of dialytic treatment. RESULTS: Patients requiring parathyroidectomy slept fewer hours (P < .001), had a higher prevalence of sleep disorders (P < .001), and were more often insomniac (P < .001). CONCLUSIONS: This study indicates that patients on hemodialysis requiring parathyroidectomy for intractable hyperparathyroidism comprise a good model for investigating the causative role of PTH on disordered sleep, and that these patients have very poor sleep. These data support recent findings on the prevalence of sleep disorders in dialyzed patients with insuppressible hyperparathyroidism.

Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial.

OBJECTIVES: We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy. BACKGROUND: Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure (HF), but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking. METHODS: A total of 114 dialysis patients with dilated cardiomyopathy were randomized to receive either carvedilol or placebo in addition to standard therapy. A first analysis was performed at one year and was followed by an additional follow-up period of 12 months. RESULTS: Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling, with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group. At two years, 51.7% of the patients died in the carvedilol group, compared with 73.2% in the placebo group (p < 0.01). Furthermore, there were significantly fewer cardiovascular deaths (29.3%) and hospital admissions (34.5%) among patients receiving carvedilol than among those receiving a placebo (67.9% and 58.9%, respectively; p < 0.00001). The exploratory analyses revealed that fatal myocardial infarctions, fatal strokes, and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group. A reduction in sudden deaths and pump-failure deaths was also observed, though it did not reach statistical significance. CONCLUSIONS: Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy. These data suggest the use of carvedilol in all dialysis patients with chronic HF.

Risk factors and underlying cardiovascular diseases in incident ESRD patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in dialysis patients. The aim of this study was to evaluate the prevalence of cardiovascular risk factors and of CVD on admission to hemodialysis. METHODS: Data were collected in 31 Italian clinics belonging to a clinic network using a prospective database (EuCliD), the main purpose of which is the support of quality assurance. Six hundred and thirty-six patients, mean age 63.9+/-15.4 years, admitted between January 1, 2000 and September 30, 2003, were separated into two groups on the basis of presence of CVD and observed for a median follow-up period of 16 months. RESULTS: In the CVD group, patients were significantly older and the percentage of diabetics and smokers was significantly greater than in the CVD-free group. There were no significant differences between the groups in term of uremia-related risk factors. According to logistic regression analysis evaluating the impact of traditional and nontraditional cardiovascular risk factors, only smoking habit (OR 1.87, 95% CI 1.25-2.79) and diabetes (OR 1.87, 95% CI 1.19-2.95) were associated with a higher relative risk for the presence of CVD at baseline. At the time of admission, CVD was present in 27% of patients. The following de novo development of CVD was observed: hypertensive disease (0.28 new cases/100 pt-years), ischemic heart disease (0.71 new cases/100 pt-years), other forms of heart disease (1.57 new cases/100 pt-years), disease of arteries, arterioles, etc. (1.85 new cases/100 pt-years) and cerebrovascular disease (0.71 new cases/100 pt-years). The rate of developing de novo CVD events was 3.70 per 100 patient-years. CONCLUSIONS: The prevalence of cardiovascular risk factors is already high at admission to dialysis. Despite the care provided to dialysis patients, a significant proportion of patients develop de novo CVD.

[Diuretics in heart failure and Karl Popper's turkey]. / I diuretici nell'insufficienza cardiaca e il tacchino di Karl Popper.

Heart failure and renal failure often coexist in the same patient. This condition is commonly referred to as cardiorenal syndrome. When this occurs, patient survival worsens significantly with increasing degree of renal dysfunction. Management of this complex patient poses treatment challenges because of unstable hemodynamics (the problem is to reduce congestion without affecting organ perfusion) and very high mid-term in-hospital mortality. Congestion is a typical feature of this syndrome, and use of diuretics is mandatory. Loop diuretics should be administered first. However, poor attention to pharmacodynamic and pharmacokinetic properties of loop diuretics may contribute to the development of diuretic resistance leading to iatrogenic hyponatremia. Accordingly, emphasis is given to the importance of sequential nephron blockade to reduce the number of non-responder patients to diuretics and to recognize a possible role for acquaretics.

Different involvement of right ventricular myocardial function in either physiologic or pathologic left ventricular hypertrophy: a Doppler tissue study.

The aim of the study was to analyze right ventricular (RV) myocardial function in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HC) or athletic endurance training. Doppler echocardiography and pulsed Doppler tissue imaging of the posterior septal wall, and mitral and tricuspid annulus were performed in 32 top-level endurance athletes (AT) and in 27 patients with HC, all men. LV mass index was comparable between the 2 groups. All transmitral Doppler indexes were higher in AT, whereas only tricuspid inflow peak E and E/A ratio were slightly decreased in the HC group. In the HC group, Doppler tissue analysis showed lower myocardial systolic and early-diastolic (Em) peak velocities, and longer time intervals at the level of all the analyzed segments, even after correction for age, heart rate, and LV mass index. Distinct multiple linear regression models revealed an independent positive association between RV peak Em velocity and LV end-diastolic diameter (beta coefficient = 0.72, P <.0001) in AT, and an independent inverse correlation of the same peak Em velocity of tricuspid annulus with septal thickness (beta = - 0.65, P <.001) in the HC group. Of interest, a RV Em peak velocity < 0.16 m/s differentiated AT and HC groups better than tricuspid Doppler (89% sensitivity and 93% specificity). In conclusion, Em RV myocardial function is positively influenced by preload increase in AT and negatively associated to increased septal thickness in patients with HC. Therefore, Doppler tissue imaging may represent a useful tool in the differential diagnosis between athlete's heart and HC, underlining the different involvement of RV myocardial function in either physiologic or pathologic LV hypertrophy.

Association between left ventricular structure and cardiac performance during effort in two morphological forms of athlete's heart.

AIM: The aim of the study was to evaluate in 263 competitive athletes possible correlations between changes induced by different sport activities in left ventricular (LV) structure and cardiac response during maximal physical effort. METHODS: A total of 160 top-level endurance athletes (ATE; swimmers, runners; 28+/-4 years; 98 male) and 103 strength-trained athletes (ATS; weight-lifters, body-builders; 27+/-5 years; male), selected on the basis of training protocol (dynamic vs. static exercise), underwent standard Doppler echocardiography, heart rate variability analysis and maximal exercise stress test by bicycle ergometry. M- and B-mode echocardiographic LV measurements were determined at rest, while the following functional indexes were assessed during effort: maximal heart rate (HR), maximal systolic blood pressure (SBP) and maximal workload (Watts reached by bicycle test). RESULTS: The two groups were comparable for age and sex, but ATS at rest showed higher HR, SBP, and body surface area (BSA). By echo analysis, LV mass index and ejection fraction did not significantly differ between the two groups. However, ATS showed increased sum of wall thickness (septum+posterior wall), relative wall thickness and LV end-systolic stress, while LV stroke volume and LV end-diastolic diameter (P<0.01) were greater in ATE. HR variability analysis underlined in ATE increased indexes of vagal tone (P<0.01). During maximal physical effort, ATE showed a better functional capacity, with greater maximal workload (P<0.001) reached with lower maximal HR and SBP. After adjusting for HR, age, sex, BSA and SBP, distinct multiple linear regression models evidenced in ATE independent associations of maximal effort workload with LV end-diastolic diameter (P<0.001), HR (P<0.001) at rest and LV end-systolic stress (P<0.01) were found in ATE. On the other hand, independent direct correlation of SBP max during effort with sum of wall thickness (P<0.001), BSA (P<0.05) and LV end-systolic stress (P<0.001) was evidenced in ATS. CONCLUSIONS: LV structural changes in competitive athletes represent adaptation to hemodynamic overload induced by training and are consistent with different kinds of sport activity. Work capacity during exercise is positively influenced by preload increase in ATE, while increased afterload due to isometric training in ATS determines higher systemic resistance during physical effort.

Effects of different training protocols on left ventricular myocardial function in competitive athletes: a Doppler tissue imaging study.

BACKGROUND: The aim of the study was to analyze the differences in myocardial function in case of left ventricular (LV) hypertrophy induced by either endurance or strength training in top-level athletes. METHODS: Standard Doppler echo and pulsed Doppler tissue imaging (DTI) of the interventricular septum and of the LV inferior wall were performed in 26 competitive endurance athletes (long-distance swimmers) (group A) and in 20 strength-trained athletes (short-distance swimmers) (group B). By means of DTI, the following parameters of myocardial function were assessed: the systolic peak velocities (Sm), the pre-contraction time, the contraction time, the early (Em) and late (Am) diastolic velocities, the Em/Am ratio and the relaxation time. RESULTS: The two groups were comparable for age and sex, but at rest group B showed a higher heart rate, systolic blood pressure and body surface area. The LV mass index and fractional shortening did not significantly differ between the two groups. However, group B showed an increased sum of the wall thicknesses (septum + posterior wall) (p < 0.001) and of the relative wall thickness, while the LV stroke volume and LV end-diastolic diameter (p < 0.001) were greater in group A. All transmitral Doppler indexes were higher in group A, with an increased E/A ratio. DTI analysis showed, in group A, a higher Em and Em/Am ratio as well as a longer relaxation time both at the septal and at the inferior wall levels, with comparable Sm, pre-contraction and contraction times. Distinct multiple linear regression models revealed an independent positive association between the inferior peak Em velocity and the LV end-diastolic diameter (p < 0.001) in group A, and an independent direct correlation of the inferior peak Sm velocity with the sum of the wall thicknesses (p < 0.001) and with the end-systolic stress in group B. CONCLUSIONS: The early diastolic myocardial function is positively influenced by the preload increase in group A, while an increased afterload and LV wall thickness in group B mainly seem to induce an enhancement of the regional myocardial systolic function.