Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy: A study from the French register of hypertrophic cardiomyopathy (REMY).

BACKGROUND: Our knowledge of hypertrophic cardiomyopathy (HCM) mainly originates from quarternary centres. The objective is to assess the current management of HCM patients in a large multicentre French register according to the level of expertise. METHODS AND RESULTS: A total of 1431 HCM patients were recruited across 26 (11 expert and 15 non-expert) centres in REMY, a prospective hospital-based register of adult HCM patients. A sarcomeric origin was suspected in 1284 (89.7%) patients [261 (20.3%) with a reported gene mutation, 242 (18.8%) genotype-negative], while 107 (7.5%) had a diagnosis of non-sarcomeric HCM. Patients managed in non-expert centres were older (P < 0.01) and presented more often with NYHA III/IV class dyspnoea (P < 0.01), congestive heart failure (P < 0.01), low LEVF (P < 0.01), less often with a syncope history (P < 0.01) and lower LV obstruction (P < 0.01) than patients in expert centres. Genotype positive sarcomeric aetiologies were less frequent in non-expert centres (P < 0.01). The use of diagnostic and prognostic tests as cardiac MRI (P < 0.001), genetic (P < 0.001) and alpha-galactosidase A enzyme level testing (P < 0.001), Holter ECG (P < 0.001), and exercise test (P < 0.001), was lower in non-expert centres. Septal ablation procedures using alcohol (P < 0.001) or myectomy (P < 0.001) were more frequent in expert centres. CONCLUSION: In real life practice, only a minority of HCM patients are identified as sarcomere positive as per genetic testing. The management of HCM patients varies according to the centre's level of expertise, with less access to diagnostic and prognostic tests in non-expert centres. Non-sarcomeric HCM may therefore be overlooked despite specific treatment in some aetiologies.

Right Ventricular Hypertrophy, Systolic Function, and Disease Severity in Anderson-Fabry Disease: An Echocardiographic Study.

BACKGROUND: Right ventricular (RV) involvement has been described in Anderson-Fabry disease (AFD), especially in patients with established Fabry cardiomyopathy (FC). However, few and controversial data on RV systolic function are available, and there are no specific tissue Doppler studies. METHODS: Detailed echocardiographic examinations were performed in 45 patients with AFD. FC, defined as maximal left ventricular wall thickness ≥ 15 mm, was present in 12. The Mainz Severity Score Index was calculated for each patient. Pulsed tissue Doppler was applied to the RV free wall at the tricuspid annular level and at the septal and lateral corners at the mitral annular level to obtain systolic tissue Doppler velocities (RV Sa, septal Sa, and lateral Sa, respectively). Twelve patients with amyloid light-chain cardiac amyloidosis were studied as a control group. RESULTS: Echocardiography revealed RV hypertrophy (RVH) in 31% of patients with AFD, all but one of whom were male and all of whom had concomitant left ventricular hypertrophy (LVH). All patients with AFD had normal RV fractional area change (47.9 ± 6.5%) and tricuspid annular plane systolic excursion (21.7 ± 3.2 mm) and all but one also had normal RV Sa (13.2 ± 2.2 cm/sec). RVH positively correlated with indices of LVH (r = 0.8, P = .0001, for all parameters evaluated), as well as with Mainz Severity Score Index (r = 0.70, P = .0001). Septal and lateral Sa were decreased in almost all patients (means, 7.7 ± 1.8 and 7.9 ± 1.9 cm/sec, respectively), irrespective of the presence of LVH. Compared with control subjects with cardiac amyloidosis, patients with FC showed better indices of RV systolic function (P < .001 for all: tricuspid annular plane systolic excursion, RV fractional area change, and RV Sa) despite similar RV wall thickness (6.2 ± 1.2 vs 6.9 ± 1.9 mm, P = NS). CONCLUSIONS: RVH is common in patients with AFD and correlates with disease severity and LVH. RVH, however, does not significantly affect RV systolic function. Patients with FC have better RV systolic function compared with those with cardiac amyloidosis with similar levels of RV thickness. The combination of low LV Sa values and normal RV Sa values might be helpful in the differential diagnosis of infiltrative heart disease.

Effect of Remote Ischemic Preconditioning on Platelet Activation Induced by Coronary Procedures.

In this study, we aim to assess whether remote ischemic preconditioning (RIPC) reduces platelet activation during coronary angiography (CA) and/or percutaneous coronary interventions. We studied 30 patients who underwent CA because of a suspect of stable angina. Patients were randomized to RIPC (3 short episodes of forearm ischemia) or sham RIPC (controls) before the procedure. Blood samples were collected at baseline, at the end of the procedure, and 24 hours later. Monocyte-platelet aggregate (MPA) formation and platelet CD41 in the MPA gate and CD41 and CD62 expression in the platelet gate were assessed by flow cytometry, in the absence and in the presence of adenosine diphosphate (ADP) stimulation. A significant increase in platelet activation occurred during the invasive procedure in controls, which persisted at 24 hours. However, compared with controls, RIPC group showed no or a lower increase in platelet variables, including MPA formation (p <0.0001) and CD41 (p = 0.002) in the MPA gate and CD41 (p <0.0001) and CD62 (p = 0.002) in the platelet gate. ADP increased platelet activation at baseline, but did not further increase platelet reactivity during the invasive procedure in either groups. Percutaneous coronary interventions, performed in 10 patients (6 in the RIPC group and 4 in controls), did not have any further significant effect on platelet activation and reactivity compared with CA alone. In conclusion, RIPC reduces platelet activation occurring during CA. In contrast, no effects were observed on platelet response to ADP stimulation, probably related to the administration of an ADP antagonist in all patients.

Use of T-wave alternans in identifying patients with coronary artery disease.

AIMS: Microvolt T-wave alternans (MTWA) has been found to predict fatal events in patients with coronary artery disease (CAD). In a previous study, we found that MTWA values are higher in patients with CAD, compared with apparently healthy individuals. In this study, we assessed the relation between CAD and MTWA in patients with a diagnosis based on coronary angiography results. METHODS: We studied 98 consecutive patients undergoing coronary angiography for suspected CAD. All patients underwent a maximal exercise stress test (EST), and MTWA was measured in the precordial ECG leads. Patients were divided into three groups: 40 patients without any significant (>50%) stenosis (group 1); 47 patients with significant stenosis (group 2); and 11 patients with a previous percutaneous coronary intervention (PCI) who had no evidence of restenosis (group 3). EST was repeated after 1 month in 24 group 2 patients who underwent PCI and in 17 group 1 patients. RESULTS: MTWA was significantly higher in group 2 (58.7 ±â€Š24 µV) compared with group 1 (34.2  ±â€Š15 µV, P < 0.01) and group 3 (43.2 ±â€Š24 µV, P < 0.05). An MTWA greater than 60 µV had 95% specificity and 82% positive predictive value for obstructive CAD. At 1-month follow-up, MTWA decreased significantly in patients treated with PCI (from 61.3 ±â€Š22 to 43.5 ±â€Š17 µV; P < 0.001), but not in group 1 patients (from 50.5 ± 22 to 44.3 ±â€Š19 µV, P = 0.19). CONCLUSION: MTWA is increased in patients with obstructive CAD and is reduced by coronary revascularization. An assessment of MTWA can be helpful in identifying which patients with suspected CAD are likely to show obstructive CAD on angiography.

Effect of remote ischemic preconditioning on platelet activation and reactivity induced by ablation for atrial fibrillation.

BACKGROUND: Radiofrequency ablation of atrial fibrillation has been associated with some risk of thromboembolic events. Previous studies showed that preventive short episodes of forearm ischemia (remote ischemic preconditioning [IPC]) reduce exercise-induced platelet reactivity. In this study, we assessed whether remote IPC has any effect on platelet activation induced by radiofrequency ablation of atrial fibrillation. METHODS AND RESULTS: We randomized 19 patients (age, 54.7±11 years; 17 male) undergoing radiofrequency catheter ablation of paroxysmal atrial fibrillation to receive remote IPC or sham intermittent forearm ischemia (control subjects) before the procedure. Blood venous samples were collected before and after remote IPC/sham ischemia, at the end of the ablation procedure, and 24 hours later. Platelet activation and reactivity were assessed by flow cytometry by measuring monocyte-platelet aggregate formation, platelet CD41 in the monocyte-platelet aggregate gate, and platelet CD41 and CD62 in the platelet gate in the absence and presence of ADP stimulation. At baseline, there were no differences between groups in platelet variables. Radiofrequency ablation induced platelet activation in both groups, which persisted after 24 hours. However, compared with control subjects, remote IPC patients showed a lower increase in all platelet variables, including monocyte-platelet aggregate formation (P<0.0001), CD41 in the monocyte-platelet aggregate gate (P=0.002), and CD41 (P<0.0001) and CD62 (P=0.002) in the platelet gate. Compared with control subjects, remote IPC was also associated with a significantly lower ADP-induced increase in all platelet markers. CONCLUSIONS: Our data show that remote IPC before radiofrequency catheter ablation for paroxysmal atrial fibrillation significantly reduces the increased platelet activation and reactivity associated with the procedure.

Endothelial and platelet function in children with previous Kawasaki disease.

We investigated whether children with a previous Kawasaki disease (KD) have evidence of abnormal vascular and/or platelet function. We included 14 patients with previous KD and 14 matched controls. We assessed endothelial function by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary microvascular function by coronary blood flow response (CBFR) to cold pressor test, and platelet reactivity by measuring monocyte-platelet aggregates (MPAs) and CD41-platelet expression by flow cytometry. No differences were found between the groups in FMD, cIMT, or CBFR to cold pressor test. The MPAs were similar in patients with KD and controls. CD41-platelet expression, however, was significantly increased in patients with KD compared with controls, both at rest (14.3 ± 1.9 vs 12.4 ± 1.9 mean fluorescence intensity [mfi], P = .01) and after adenosine diphosphate stimulation (19.3 ± 1.3 vs 17 ± 1.7 mfi, P < .001). In conclusion, children with a previous episode of KD showed increased platelet activation, compared with healthy participants despite no apparent vascular abnormality at follow-up.

Prognostic role of heart rate variability in patients with ST-segment elevation acute myocardial infarction treated by primary angioplasty.

OBJECTIVES: The aim of our study was to assess the prognostic value of heart rate variability (HRV) in ST-segment elevation acute myocardial infarction (STEMI) patients treated by percutaneous transluminal coronary angioplasty (PTCA) and optimal medical therapy. METHODS: We enrolled 182 consecutive patients with a first STEMI (59.1 ± 11 years; 82.4% men) treated by primary PTCA. HRV was assessed on 24-hour Holter ECG recordings before discharge and 1 and 6 months after discharge. The primary end point was the occurrence of major clinical events (MCE), defined as death or new acute myocardial infarction (AMI). RESULTS: At a follow-up of 42 ± 23 months, MCE occurred in 14 patients (7.6%; 3 deaths and 11 re-AMIs). HRV parameters before discharge were significantly lower in patients with MCE, with standard deviation of all RR intervals (SDNN) and very low frequency and low frequency (LF) amplitude being the most predictive variables. HRV assessed at follow-up instead did not significantly predict MCE. At multivariate analysis, only SDNN (HR 0.97; p = 0.02) and LF (HR 0.90; p = 0.04) remained significantly associated with MCE. Lower tertile SDNN and LF values were associated with a multivariate HR of 3.91 (p = 0.015) and of 2.92 (p = 0.048), respectively. Similar results were observed considering re-AMI only as the end point. CONCLUSIONS: In STEMI patients treated by PTCA, HRV assessed before discharge was an independent predictor of MCE and re-AMI.

Prevalence and clinical correlates of early repolarization and J wave in a large cohort of subjects without overt heart disease.

BACKGROUND: Recent studies have suggested that early repolarization (ER) is associated with increased risk of ventricular tachyarrhythmias. Early repolarization in these studies, however, was defined as J-wave (terminal QRS slurring or notching) or J-point elevation rather than typical ST-segment elevation (STE). Prevalence and characteristics of these different findings in the general population are poorly known. In this study, we assessed prevalence and correlates of STE typical of ER and of J wave in a large population of noncardiac subjects. METHODS: We prospectively collected electrocardiograms of 4176 consecutive subjects without heart disease at our hospital. RESULTS: Early repolarization was found in 84 subjects (2.0%) and J wave in 663 (15.9%). Among ER subjects, a J wave was present in 60 (71.4%). Variables independently associated with both ER and J wave included young age, male sex, and lower heart rate. There was no increased history of symptoms (palpitations and syncope) possibly related to arrhythmias in STE or J-wave subjects. CONCLUSIONS: Typical ER pattern and J wave are common in noncardiac subjects, particularly in young people, and are not associated with symptoms potentially related to arrhythmias.

Association of heart rate variability with arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events. METHODS AND RESULTS: We studied 30 consecutive patients (17 males; 45.4 ± 18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19 ± 7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039). CONCLUSIONS: Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events.

T-wave alternans in apparently healthy subjects and in different subsets of patients with ischaemic heart disease.

AIMS: Microvolt T-wave alternans (TWA) predicts arrhythmic risk in patients with ischaemic heart disease (IHD). While TWA has widely been assessed by the spectral method, it has been poorly characterized in healthy people as well as in IHD patients by the modified moving average (MMA) method. METHODS AND RESULTS: We enrolled 729 consecutive subjects, referred for exercise stress test (EST). T-wave alternans was assessed by the MMA method, considering all 12 electrocardiogram (ECG) leads (TWA_tot) or the 6 ECG pre-cordial leads only (TWA_prec). Patients were divided into five groups: (i) no history of IHD and normal EST (Group 1); (ii) no history of IHD but positive EST (Group 2); (iii) ischaemic heart disease without any acute myocardial infarction [AMI (Group 3)]; (iv) old AMI (Group 4); (v) recent AMI (Group 5). T-wave alternans values >95th percentile of those measured in Group 1 were considered 'abnormal'. The 95th percentile of TWA values in Group 1 was 75 µV for TWA_tot and 65 µV for TWA_prec. T-wave alternans values and prevalence of abnormal TWA increased from Groups 1-2 to Group 5 (P< 0.00001 for both). Group 4 and Group 5, compared with Group 1, showed a significant higher prevalence of abnormal values of TWA_tot [odds ratio (OR) 1.70 (P= 0.002), and 2.07 (P= 0.01), respectively] and TWA_prec [OR 1.51 (P= 0.02) and 2.37 (P= 0.003), respectively] at multivariable analysis. In IHD patients EST-induced ischaemia did not influence TWA; in AMI patients, impaired left ventricular function was associated with higher TWA values. CONCLUSIONS: In healthy people, TWA_tot and TWA_prec were ≤75 and ≤65 µV, respectively, in 95% of subjects. In IHD patients TWA values were higher compared with healthy individuals; a history of AMI was independently associated with abnormal TWA values.

Effect of shift work on endothelial function in young cardiology trainees.

BACKGROUND: Long-term shift work (SW) is associated with an increase in cardiovascular disease (CVD). Previous studies have shown that prolonged SW is associated with endothelial dysfunction, suggesting that this abnormality may contribute to the SW-related increase in cardiovascular risk. The immediate effect of SW on endothelial function in healthy subjects, however, is unknown. DESIGN: We studied endothelial function and endothelium-independent function in 20 healthy specialty trainees in cardiology at our Institute, without any cardiovascular risk factor (27.3 ± 1.9 years, nine males), at two different times: (1) after a working night (WN), and (2) after a restful night (RN). The two test sessions were performed in a random sequence. METHODS: Endothelial function was assessed by measuring brachial artery dilation during post-ischaemic forearm hyperaemia (flow-mediated dilation, FMD). Endothelium-independent function in response to 25 µg of sublingual glyceryl trinitrate (nitrate-mediated dilation, NMD) was also assessed. RESULTS: FMD was 8.02 ± 1.4% and 8.56 ± 1.7% after WN and RN, respectively (p = 0.025), whereas NMD was 10.5 ± 2.1% and 10.4 ± 2.0% after WN and RN, respectively (p = 0.48). The difference in FMD between WN and RN was not influenced by the numbers of hours slept during WN (<4 vs >4 hours) and by the duration of involvement of specialty trainees in nocturnal work (<12 vs >12 months). CONCLUSIONS: Our study shows that in healthy medical residents, without any cardiovascular risk factor, FMD is slightly impaired after WN compared to RN. Disruption of physiological circadian neuro-humoral rhythm is likely to be responsible for this adverse vascular effect.

[Coronary microvascular dysfunction. An update]. / In tema di disfunzione del microcircolo coronarico.

Several studies in the last years have shown that a dysfunction of coronary microcirculation may be responsible for abnormalities in coronary blood flow and some clinical pictures. Coronary microvascular dysfunction, in absence of other coronary artery abnormalities, can cause anginal symptoms, resulting in a condition named microvascular angina (MVA). MVA can occur in a chronic form, predominantly related to effort (stable MVA), more frequently referred as cardiac syndrome X, or in an acute form, most frequently ensuing at rest, which simulates an acute coronary syndrome (unstable MVA). The main abnormalities characterizing these two forms of MVA consist of an impaired vasodilation and an increased vasoconstriction of small resistive coronary arteries, respectively. The mechanisms responsible for stable MVA are still unclear, but seem to include, together with the known traditional cardiovascular risk factors, an abnormally increased cardiac adrenergic activity. The prognosis of stable MVA is good, but some patients have progressive worsening of symptoms. Clinical outcome of patients with unstable MVA is substantially unknown, as there are no specific studies about this population. Treatment of stable MVA includes traditional anti-ischemic drugs as first step; in case of persisting symptoms several other drugs have been proposed, including xanthine derivatives, ACE-inhibitors, statins and, in women, estrogens. Severe forms of intense constriction (or spasm) of small coronary arteries may cause transmural myocardial ischemia, as the microvascular form of variant angina and the tako-tsubo syndrome.