Antonio Cirò

Effects of Heart Rate Changes on Arterial Distensibility in Humans

Abstract—In rats, an increase in heart rate by pacing is accompanied by progressive large-artery stiffening. Whether this is also the case in humans is unknown. We enrolled 20 patients who were chronically implanted with a pacemaker because of atrioventricular block or sick sinus syndrome. Arterial distensibility was measured by an echo-tracking device. In 10 patients, the evaluation was performed on the radial artery by using continuous finger blood pressure measurements, whereas in the remaining 10 patients, the common carotid artery was studied with a semiautomatic measure of brachial artery blood pressure. Diastolic diameter, systodiastolic diameter change, and distensibility were obtained at baseline (heart rate 63±2 beats/min) and after atrial and ventricular sequential pacing at a heart rate of 90 and 110 beats/min. At baseline, the diameter was 7.8±0.3 mm in the carotid artery and 2.4±0.1 mm in the radial artery; the respective systodiastolic diameter change values were 375.4±31.0 and 55.9±9.0 (&mgr;m) and the distensibility values were 1.4±0.1 and 0.7±0.1 (1/mm Hg 10−3). Blood pressure and diameter were not significantly modified by increasing heart rate, which markedly modified systodiastolic diameter change and distensibility. In the radial artery, distensibility was reduced by 47% (P <0.05) at a heart rate of 90 beats/min with no further reduction at 110 beats/min. In the carotid artery, distensibility was reduced by 20% at a heart rate of 90 beats/min (P <0.05) with a further reduction at 110 beats/min (45%, P <0.05). These data provide the first evidence in humans that acute increases in heart rate markedly affect arterial distensibility and that this occurs in both large- and middle-size muscle arteries within the range of “normal” heart rate values.

Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure

Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure–dependent sympathoexcitation is uncertain. In 11 heart failure patients (mean±SEM age, 68.4±1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration ≥130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and ≈10 weeks after successful resynchronization therapy. Ten age- and NYHA class–matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1±3.6 vs 30.7±3.0 bs/min, −30.5%, P<0.02) and as burst frequency corrected for heart rate (68.3±5.9 vs 47.3±4.3 bs/100 beats, −32.1%, P<0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications.

Effects of heart rate changes on arterial distensibility in humans - Response

Effects of Heart Rate Changes on Arterial Distensibility in Humans To the Editor: Dependence of arterial stiffness on heart rate, claimed by Giannattasio et al,1 runs counter to classic studies, which were previously discussed in relation to conflicting data obtained with one method used to measure aortic pulse wave velocity.2 There is a potential flaw in the method applied by Giannattasio et al in their determination of carotid and radial artery distensibility at different heart rates. They measured diameter change of the target artery, but pressure pulsation at a distal site (brachial pressure for carotid, finger pressure for radial artery). Errors inherent in distal pressure measurement have been stressed in a recent consensus document3 but were considered by authors1 to be minimal. We disagree. In similar studies by Wilkinson et al,4 there was an average 35% fall in central pulse pressure, compared with brachial, when heart rate was increased from 60 to 110/min by pacing. Giannattasio et al quoted an early evaluation of the Finapres system and considered this accurate for their purposes, but this study did not test response to change in heart rate. In a later manuscript by the developers of Finapres,5 a marked heart rate difference was noted for systolic pressure between noninvasive finger and brachial intraarterial pressure (20 mm Hg difference for heart rate change of 40 bpm). The differences in distensibility calculated by Giannattasio et al were at the margin of statistical significance (P 0.05). Given the problems in estimating pulse pressure at the site of diameter measurement and the likelihood that this was overestimated, we continue to rely on the previous work,2,3 which showed no significant dependence of arterial stiffness on heart rate.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). &bgr;-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

La frequenza cardiaca e la prognosi nello scompenso cardiaco acuto e cronico

Heart rate (HR) is not only a physical sign but also a biomarker. High HR in several cardiac disorders is associated with increased mortality. In heart failure (HF), HR represents an important therapeutic target, both in the acute and chronic phase. Beta-blockers are a milestone of recommended treatments in HF patients with reduced ejection fraction. However, hemodynamic profile or intolerance may limit the use or the optimization of beta-blocker treatment, both during hospitalization and outpatient follow-up. More recently, ivabradine has become available, a drug that lowers HR by blocking the I(f) current in the pacemaker cells at the sinoatrial node level. In the SHIFT trial, ivabradine was shown to improve the outcome of patients with chronic HF, in sinus rhythm, with HR >70 b/min while on beta-blockers. Preliminary data have shown that this drug has a good safety profile and lowers effectively HR even during hospitalization due to worsening HF. However, further studies are warranted to understand if an earlier administration of ivabradine can lead to a better prognosis beyond symptom control and improved hemodynamics. In patients with atrial fibrillation and HF, the target is the restoration of sinus rhythm, alternatively rate control should be pursued with beta-blockers, amiodarone or digitalis, even if there is no clear evidence of an association between ventricular rate response in patients with atrial fibrillation at discharge after an HF hospitalization and major cardiovascular events. In this review, the studies that point to a role of HR both as a biomarker and a therapeutic target in patients with acute and chronic HF are described. In addition, the proportions of patients who do not reach target HR values at discharge after an acute decompensated HF episode or in the chronic phase are evaluated based on the Italian registries.

Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration

BACKGROUND Ambulatory Advanced Heart Failure (AAHF) is characterized by recurrent HF hospitalizations, escalating diuretic requirements, intolerance to neurohormonal antagonists, end-organ dysfunction, short-term reduced life expectancy despite optimal medical management (OMM). The role of intermittent inotropes in AAHF is unclear. The RELEVANT-HF registry was designed to obtain insight on the effectiveness and safety of compassionate scheduled repetitive 24-hour levosimendan infusions (LEVO) in AAHF patients. METHODS 185 AAHF NYHA class III-IV patients, with ≥2 HF hospitalizations/emergency visits in the previous 6 months and systolic dysfunction, were treated with LEVO at tailored doses (0.05-0.2 μg/kg/min) without prior bolus every 3-4 weeks. We compared data on HF hospitalizations (percent days spent in hospital, DIH) in the 6 months before and after treatment start. RESULTS Infusion-related adverse events occurred in 23 (12.4%) patients the commonest being ventricular arrhythmias (16, 8.6%). During follow-up, 37 patients (20%) required for clinical instability treatment adjustments (decreases in infusion dose, rate of infusion or interval). From the 6 months before to the 6 months after treatment start we found lower DIH (9.4 (8.2) % vs 2.8 (6.6) %, p < 0.0001), cumulative number (1.3 (0.6) vs 1.8 (0.8), p = 0.0001) and length of HF admissions (17.4 (15.6) vs 21.6 (13.4) days, p = 0.0001). One-year survival was 86% overall and 78% free from death/LVAD/urgent transplant. CONCLUSIONS In AAHF patients, who remain symptomatic despite OMM, LEVO is well tolerated and associated with lower overall length of hospital stay during six months. This multicentre clinical experience underscores the need for a randomized controlled trial of LEVO impact on outcomes in AAHF patients.

Sacubitril/Valsartan in “Field Practice” Patients with Advanced Heart Failure: A Monocentric Italian Experience

Patients with advanced heart failure (HF) experience a continuous decline in quality of life and have a very poor prognosis. Moreover, due to numerous comorbidities present in these patients, transplantation and left ventricular assist devices are usually impracticable in clinical practice. In this challenging setting, administration of inotropic agents may be the only possible therapy; however, this treatment requires frequent hospitalizations. Our hypothesis is that sacubitril/valsartan, given its marked efficacy and manageability, can be safely used in clinical practice in this setting, potentially reducing hospitalizations and the need for inotropic support. We report here our experience in a small series of patients with advanced HF treated with sacubitril/valsartan.