Roberto Nerla

Effects of Ivabradine and Ranolazine in Patients With Microvascular Angina Pectoris

Patients with microvascular angina (MVA) often have persistence of symptoms despite full classical anti-ischemic therapy. In this study, we assessed the effect of ivabradine and ranolazine in MVA patients. We randomized 46 patients with stable MVA (effort angina, positive exercise stress test [EST], normal coronary angiography, coronary flow reserve <2.5), who had symptoms inadequately controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily), ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after treatment. Coronary microvascular dilation in response to adenosine and to cold pressor test and peripheral endothelial function (by flow-mediated dilation) were also assessed. Both drugs improved SAQ items and EuroQoL scale compared with placebo (p <0.01 for all), with ranolazine showing some more significant effects compared with ivabradine, on some SAQ items and EuroQoL scale (p <0.05). Time to 1-mm ST-segment depression and EST duration were improved by ranolazine compared with placebo. No effects on coronary microvascular function and on flow-mediated dilation were observed with drugs or placebo. In conclusion, ranolazine and ivabradine may have a therapeutic role in MVA patients with inadequate control of symptoms in combination with usual anti-ischemic therapy.

Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function

BACKGROUND AND AIMS To assess the effects of bariatric surgery (BS) on peripheral endothelial function and on coronary microvascular dilator function. METHODS AND RESULTS We studied 50 morbidly obese patients (age 38 ± 9, 13 M) who underwent BS and 20 comparable obese controls (age 41 ± 11, 6 M) without any evidence of cardiovascular disease. Peripheral vascular dilator function was assessed by brachial artery diameter changes in response to post-ischemic forearm hyperaemia (flow-mediated dilation, FMD). Coronary microvascular function was assessed by measuring coronary blood flow (CBF) velocity response to i.v. adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery by transthoracic Doppler echocardiography. The tests were performed at baseline and at 3-month follow-up. At baseline, FMD and CBF response to adenosine and CPT were similar in the 2 groups. Compared to baseline, FMD at follow-up improved significantly in BS patients (5.9 ± 2.7% to 8.8 ± 2.4%, p < 0.01), but not in controls (6.3 ± 3.2% vs. 6.4 ± 3.1%, p = 0.41). Similarly, a significant improvement of CBF response to adenosine (1.63 ± 0.47 to 2.45 ± 0.57, p < 0.01) and to CPT (1.43 ± 0.26 to 2.13 ± 0.55, p < 0.01) was observed in BS patients but not in controls (1.55 ± 0.38 vs. 1.53 ± 0.37, p = 0.85; and 1.37 ± 0.26 vs. 1.34 ± 0.21, p = 0.48, respectively). The favourable vascular effects of BS were similar independently of the presence and changes of other known cardiovascular risk factors and of basal values and changes of serum C-reactive protein levels. CONCLUSIONS Our data show that, in morbidly obese patients, together with peripheral endothelial function, BS also improves coronary microvascular function. These effects suggest global improvement of vascular function which can contribute significantly to the reduction of cardiovascular risk by BS reported in previous studies.

Cardiac adrenergic nerve function and microvascular dysfunction in patients with cardiac Syndrome X

Objective: To assess whether abnormalities in cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX). Setting: University hospital. Patients: 29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied. Interventions: Planar and single photon emission computed tomography (SPECT) MIBG myocardial scintigraphy was performed in all subjects. Coronary flow response (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending (LAD) coronary artery was assessed in all CSX patients and in 12 controls by transthoracic Doppler echocardiography. Main outcome measures: Abnormalities in cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no healthy control (p<0.001). Compared to controls, CSX patients showed a lower heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p<0.001) and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to adenosine (3.31 (1.1) vs 1.94 (0.6), p<0.001) and CFR to CPT (2.35 (0.5) vs 1.63 (0.4), p<0.001) were lower in CSX patients than in controls. In CSX patients, however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r = 0.17; p = 0.38) and to CPT (r = −0.28; p = 0.13), as well as between MIBG uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and to CPT (r = 0.06; p = 0.73). Conclusion: Our data show striking abnormalities in cardiac adrenergic nerve function and in coronary microvascular function in CSX patients. However, no significant relation between the two abnormalities was found. Further studies are needed to clarify the mechanisms and the role of MIBG defects in CSX patients.

Inflammation‐related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function

Abstract.  Lanza GA, Barone L, Scalone G, Pitocco D, Sgueglia GA, Mollo R, Nerla R, Zaccardi F, Ghirlanda G, Crea F (Istituto di Cardiologia; and Università Cattolica del Sacro Cuore, Roma; Italy). Inflammation‐related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function. J Intern Med 2010; 269: 118–125.

Clinical Correlates and Prognostic Value of Flow Mediated Dilation in Patients With Non-ST Segment Elevation Acute Coronary Syndromes

Endothelial dysfunction can predict cardiovascular outcomes in several populations of patients. The aim of this study was to assess the severity, time course, and clinical implications of endothelial dysfunction in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Sixty patients with NSTE ACS (mean age 62 ± 8 years, 44 men) and 40 controls with stable coronary artery disease (CAD) (mean age 63 ± 10 years, 27 men) were studied. In patients with NSTE ACS and in those with stable CAD, endothelial function was assessed <12 hours after admission and at 3-month follow-up by measuring right brachial artery dilation after 5 minutes of forearm ischemia (flow-mediated dilation [FMD]). Clinical outcomes were assessed after a median follow-up period of 32 months (range 14 to 36). The primary end point was a combination of cardiac death or readmission for new ACS or recurrence of angina pectoris. FMD on admission was significantly lower in patients with NSTE ACS compared to those with stable CAD (2.1 ± 1.2% vs 4.8 ± 1.9%, p <0.001). FMD improved significantly at 3-month follow-up in patients with NSTE ACS, becoming comparable to that in patients with stable CAD (5.7 ± 2.6% vs 5.5 ± 1.7%, p = 0.93). During follow-up, 14 cardiac events (23%) occurred in patients with NSTE ACS. On multivariate analysis, only diabetes (hazard ratio 18.1, 95% confidence interval 3.9 to 83.9, p <0.001) and FMD at 3 months (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, p = 0.04) were independent predictors of the primary end point in patients with NSTE ACS. In conclusion, endothelial function is markedly impaired in the acute phase of NSTE ACS but improves significantly at 3-month follow-up. In patients with NSTE ACS, FMD at 3 months after the acute event is a significant independent predictor of cardiac outcomes.

Peripheral Arterial Function and Coronary Microvascular Function in Patients with Variant Angina

Objectives: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS). Methods: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively. Results: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography. Conclusions: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation.

Coronary microvascular dysfunction after elective percutaneous coronary intervention: correlation with exercise stress test results

OBJECTIVES We assessed whether exercise stress test (EST) results are related to the presence of coronary microvascular dysfunction (CMVD) in patients undergoing elective percutaneous coronary intervention (PCI). BACKGROUND Previous studies showed that EST is poorly reliable in predicting restenosis after PCI; some studies also showed CMVD in the territory of the treated vessel. METHODS We studied 29 patients (age 64 ± 6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the left anterior descending (LAD) coronary artery, undergoing successful PCI with stent implantation. EST and assessment of coronary microvascular function were performed 24h, 3 months and 6 months after PCI. Coronary blood flow (CBF) response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography. RESULTS Patients with ST-segment depression ≥ 1 mm at EST performed 24h after PCI (n=11, 38%) showed a lower CBF response to adenosine compared to those with negative EST (1.65 ± 0.4 vs. 2.11 ± 0.4, respectively, p=0.003), whereas the difference in CBF response to CPT was not significant (1.44 ± 0.4 vs. 1.64 ± 0.3, respectively; p=0.11). At 3-month and 6-month follow-up a positive EST was found in 12 (41%) and 13 (44%) patients, respectively; patients with positive EST also had lower CBF response to adenosine compared to those with negative EST (3 months: 1.69 ± 0.3 vs. 2.20 ± 0.3, respectively; 6 months: 1.66 ± 0.2 vs. 2.32 ± 0.3, respectively; p<0.001 for both). CONCLUSIONS Positive EST after elective successful PCI consistently reflects impairment of hyperemic CBF due to CMVD, which persists over a follow-up period of 6 months.

Cardiac adrenergic nerve function in patients with cardiac syndrome X.

Background We previously found a severe impairment of cardiac uptake of 123I-metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, on myocardial scintigraphy in a small group of patients with cardiac syndrome X (CSX), suggesting a dysfunction of cardiac adrenergic nerve fibres. In this study, we assessed the consistency of these previous findings in a larger group of these patients. Methods Planar and single-photon emission computed tomography MIBG myocardial scintigraphy was performed in 40 CSX patients (58 ± 7 years, 17 men). Cardiac MIBG uptake was measured by the heart/mediastinum ratio and by a single-photon emission computed tomography regional cardiac MIBG uptake defect score (higher values = lower uptake). As a control group, we studied 20 healthy individuals (56 ± 6 years, nine men). An exercise stress 99mTc-SestaMIBI myocardial scintigraphy was performed in 34 CSX patients (85%). Results Cardiac MIBG defects were observed in 30 patients (75%), with nine (22.5%) showing no cardiac MIBG uptake at all. Compared with controls, CSX patients showed a significantly lower heart/mediastinum ratio (1.70 ± 0.35 vs. 2.1 ± 0.22, P < 0.001) and a higher cardiac MIBG defect score (27 ± 25 vs. 4.4 ± 2.5, P < 0.001). No differences were found in lung MIBG uptake between the two groups. Reversible perfusion defects on stress myocardial scintigraphy were found in 17 out of 34 CSX patients (50%), all of whom also had abnormal cardiac MIBG uptake; cardiac MIBG uptake abnormalities were also present in nine of 17 patients with normal perfusion scintigraphic images. Cardiac MIBG uptake findings were similar in our first 12 patients and in the 28 patients studied subsequently. Conclusion Our data show a relevant impairment of cardiac MIBG uptake in patients with CSX, suggesting that functional abnormalities in cardiac adrenergic nerve function may play a significant role in the mechanisms responsible for the syndrome.

Out-of-hospital cardiac arrest: contemporary management and future perspectives

### Learning objectives ### The scale of the problem Out-of-hospital cardiac arrest (OOHCA) remains a leading cause of death in developed countries.1 In spite of clear improvements in treatments and patient pathways, all-comer survival is still <10%,1 ,2 with significant variability in registry outcomes dependent on geography, sophistication of ambulance services and the clinical experience of treating centres.3 Between 2013 and 2014, of 28 000 reported OOHCA cases in England, the overall survival to hospital discharge was only 8.7%.4 However, these data encompass all patient groups, including those with and without return of spontaneous circulation (ROSC), those with and without ‘shockable heart rhythms’ (SHR) and patients with highly variable time delays to implementation of resuscitation—all important factors that significantly skew results and outcomes. These factors also challenge the interpretation of the available literature. ### The ‘chain of survival’ Approximately 80% of OOHCAs occur at home and 20% in public places.5 The current rate of initial bystander cardiopulmonary resuscitation (CPR) in England is reported as 43%,6 including both spontaneous bystander-initiated CPR and bystander-performed CPR prompted by Emergency Services over the telephone. Approximately 20% of OOHCA patients are in an SHR (ie, treatable by defibrillation) by the time the emergency …

Clinical and procedural impact of aortic arch anatomic variants in carotid stenting procedures

To evaluate the impact of aortic arch variants in patients undergoing carotid artery stenting (CAS).