Carlo Rengo

Alterations in Ultrasonic Backscatter During Exercise-Induced Myocardial Ischemia in Humans

BACKGROUND Experimentally induced myocardial ischemia in animals causes tissue modifications that alter characteristics of the ultrasonic beam backscattered from the myocardial muscle. Alterations of backscatter parameters have been evidenced in human subjects with acute or remote myocardial infarction and during ischemia induced by angioplasty balloon occlusion or pharmacological stimuli. The effects of transient effort ischemia in humans have not been reported. The purpose of this study is to assess ultrasonic backscatter parameter changes induced by transient effort myocardial ischemia in human subjects. METHODS AND RESULTS Nineteen patients with single left anterior descending coronary stenosis and 15 healthy subjects underwent ultrasonic backscatter analysis (parasternal long-axis view) at rest, immediately after a supine stress test, and 30 minutes later. Two windows were selected in each ultrasonic study: one encompassing the septum; the other, the posterior wall. Integrated backscatter was computed throughout the cardiac cycle, yielding a power curve relative to the midmyocardial region of the myocardial wall (excluding pericardial and endocardial borders). Five parameters were computed from the backscatter power curve: the maximum-minimum difference, amplitude and phase of the first harmonic Fourier fitting, phase-weighted amplitude, and time-averaged integrated backscatter difference from rest (an index of overall myocardial reflectivity). This protocol allowed comparison of the backscatter data from a region at risk of ischemia (the septum) with that from a region normally perfused (posterior wall) and a comparison with the same regions of the control group during the three ultrasonic studies. All backscatter indexes in the septum were altered significantly by exercise compared with rest values, whereas no changes were found in the normally perfused posterior wall or in the septum of the control group. All modified parameters returned to baseline values at the time of the recovery study. CONCLUSIONS These data indicate that transient, exercise-induced ischemia is associated with reduction of the cardiac cycle-dependent variation of the integrated backscatter power curve, a temporal shift in the nadir of the power curve with respect to the R wave (phase increase), and a small but detectable increase of myocardial reflectivity. These changes may be detected noninvasively in humans with ultrasonic backscatter analysis.

β-adrenergic receptor responsiveness in aging heart and clinical implications.

Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called “β-adrenergic desensitization”). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) β1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular β-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure.

Adrenal adrenoceptors in heart failure

Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CA) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being used for the treatment of this disease. Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin cell membranes. This process is regulated by adrenergic receptors (ARs): α2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and β ARs (mainly β2ARs) stimulate CA release through coupling to stimulatory Gs-proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs) regulate their signaling and function. Adrenal GRK2-mediated α2AR desensitization and downregulation are increased in HF and seem to be a fundamental regulator of CA secretion from the adrenal gland. Consequently, restoration of adrenal α2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF. This strategy could have several significant advantages over existing HF pharmacotherapies minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin–angiotensin–aldosterone and endothelin systems. The role of adrenal ARs in regulation of sympathetic hyperactivity opens interesting perspectives in understanding HF pathophysiology and in the identification of new therapeutic targets.

Portal vein pulsatility ratio provides a measure of right heart function in chronic heart failure.

Portal vein flow was recorded by color Doppler sonography in 31 patients with chronic heart failure and 18 control subjects. Compared with patients showing a forward flow (Group A), those with reversed portal vein flow (Group B) had higher prevalence of tricuspid regurgitation (75% vs. 43%), hepatic congestion (100% vs. 30%) and ascites (50% vs. 18%), and showed higher right atrial pressure (25.3 +/- 3.01 mmHg vs. 11.8 +/- 5.75 mmHg, p < 0.01). In controls, portal vein pulsatility ratio was 0.66 +/- 0.08, in Group A it was 0.46 +/- 0.28 (p < 0.01), in Group B -0.60 +/- 0.19 (p < 0.01). Portal vein pulsatility ratio negatively correlated with right atrial pressure (r = -0.87; p < 0.01). In Group A, hepatic congestion, ascites and tricuspid regurgitation were associated with a higher portal vein pulsatility. This study indicates that portal vein pulsatility ratio reflects the level of impairment of the right heart.

Diffuse Idiopathic Skeletal Hyperostosis Prevalence in Subjects With Severe Atherosclerotic Cardiovascular Diseases

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheseal sites. Several metabolic factors have been suggested to be involved in DISH development. We assessed the prevalence of DISH and its relationship to traditional vascular risk factors in a cohort of patients diagnosed with cardiovascular diseases.

Myocardial Ultrasonic Tissue Characterization in Pediatric and Adult Patients With Hypertrophic Cardiomyopathy

BACKGROUND Hypertrophic cardiomyopathy (HCM) has different clinical and prognostic aspects in young than in adult patients. This study was undertaken to determine whether these reported differences are reflected by changes in ultrasonic backscatter parameters and whether oral treatment with verapamil modifies backscatter variables in children with HCM. METHODS AND RESULTS Sixty-eight subjects underwent backscatter analysis to assess the ultrasonic myocardial reflectivity and the amplitude of the cardiac cycle-dependent variation of the backscatter power curve. Subjects were divided into four groups: 10 HCM and 23 normal subjects < 10 years old and 17 HCM and 18 normal adults. Myocardial reflectivity and amplitude of the cyclic variation were assessed in the septum and in the posterior wall of all subjects. The children with HCM were restudied after long-term oral administration of verapamil. Both children and adult patients, compared with the normal control groups, showed a significant reduction in the amplitude of the cyclic variation both in the septum and in the posterior wall. In contrast, myocardial reflectivity, although significantly increased in adult HCM patients, was unchanged in the young HCM group. Verapamil administration did not significantly alter the results in the children with HCM. CONCLUSIONS These data demonstrate that in young HCM patients, the ultrasonic myocardial reflectivity is normal, in contrast to the significant increase observed in adult patients affected by the same disease. This observation is in accord with the different clinical manifestations reported in young HCM patients and indicates an age-dependent difference in the echogenic structure of the hypertrophied myocardium in HCM.

Instruments for geriatric assessment: new multidimensional assessment approaches

During the last century the considerable increase in life expectancy has led to important demographic changes and, consequently, to new clinical scenarios. Nowadays, chronic conditions, comorbidities and socio-economic factors constitute a relevant health management issue. In particular, the definition of frail elderly individuals has proven to have a strong role in the identification of high-risk patients, their clinical management and prognosis. Reorganization of the medical system has been associated with the development of new instruments for clinical assessment, focused on clinical and socio-economic issues, resulting in a multidimensional geriatric assessment. A large number of approaches have been validated in different clinical settings and populations, until the development of multidimensional instruments demonstrated to have a crucial role in the identification of frail individuals and in their clinical management. Interestingly, some of these, such as the Multidimensional Prognostic Index (MPI), proved to play a relevant role in mortality risk stratification even in particular clinical settings such as chronic kidney disease.

Left ventricular diastolic filling in elderly hypertensive patients

Objective: To evaluate the effects of mild to moderate hypertension and of LVH on diastolic filling and other Doppler indices in the elderly.

Risk of acute myocardial infarction after transurethral resection of prostate in elderly

BackgroundBenign prostatic hyperplasia is a frequent disease among elderly, and is responsible for considerable disability. Benign prostatic hyperplasia can be clinically significant due to lower urinary tract symptoms that take place because the gland is enlarged and obstructs urine flow. Transurethral resection of the prostate remains the gold standard treatment for patients with moderate or severe symptoms who need active treatment or who either fail or do not want medical therapy. Moreover, perioperative and postoperative surgery complications as cardiovascular ones still occur. The incidence of acute myocardial infarction in patients undergoing transurethral resection of the prostate is controversial. The first studies showed an increase in mortality and relative risk of death from myocardial infarction in transurethral resection of the prostate group vs open prostatectomy but these results are in contrast with more recent data.DiscussionGiven the conflicting evidence of the studies in the literature, in this review we are going to discuss the factors that may influence the risk of myocardial infarction in elderly patients undergoing prostate surgery. We analyzed the possible common factors that lead to the development of myocardial infarction and benign prostatic hyperplasia (cardiovascular and metabolic), the stressor factors related to prostatectomy (surgical and haemodynamic) and the risk factors specific of the elderly population (comorbidity and therapies).SummaryAlthough transurethral resection of the prostate is considered at low risk for severe complications, there are several reports indicating that cardiovascular events in elderly patients undergoing this surgical operation are more common than in the general population. Several cardio-metabolic, surgical and aging-related factors may help explain this observation but results in literature are not concord, especially due to the fact that most data derive from retrospective studies in which selection bias cannot be excluded. Subsequently, further studies are necessary to clarify the incidence of acute myocardial infarction in old people.

Neuro-hormonal effects of physical activity in the elderly

Thanks to diagnostic and therapeutic advances, the elderly population is continuously increasing in the western countries. Accordingly, the prevalence of most chronic age-related diseases will increase considerably in the next decades, thus it will be necessary to implement effective preventive measures to face this epidemiological challenge. Among those, physical activity exerts a crucial role, since it has been proven to reduce the risk of cardiovascular diseases, diabetes, obesity, cognitive impairment and cancer. The favorable effects of exercise on cardiovascular homeostasis can be at least in part ascribed to the modulation of the neuro-hormonal systems implicated in cardiovascular pathophysiology. In the elderly, exercise has been shown to affect catecholamine secretion and biosynthesis, to positively modulate the renin-angiotensin-aldosterone system and to reduce the levels of plasma brain natriuretic peptides. Moreover, drugs modulating the neuro-hormonal systems may favorably affect physical capacity in the elderly. Thus, efforts should be made to actually make physical activity become part of the therapeutic tools in the elderly.