Cardiac magnetic resonance imaging in the evaluation and management of mitral valve prolapse - a comprehensive review.

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of "arrhythmic mitral valve prolapse" as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy.

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.

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.

[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.

Transthoracic echocardiography in patients undergoing mitral valve repair: comparison of new transthoracic 3D techniques to 2D transoesophageal echocardiography in the localization of mitral valve prolapse.

Successful mitral valve (MV) repair for degenerative mitral regurgitation (DMR) is mainly related to surgical expertise and MV anatomy. Although 2D echocardiography, specifically transoesophageal (TOE), provides precise information regarding MV anatomy, recent advancements in matrix technology meant a decisive step forward to the point where segmental MV analysis can be accurately performed from a noninvasive 3D transthoracic (TTE) approach. The aims of this study were: (a) to evaluate the feasibility and time required for real-time 3D TTE in a large consecutive cohort of patients with severe DMR in the assessment of MV anatomy; (b) to compare the accuracy of 3D TTE and 2D TOE versus surgical inspection in the recognition and localization of all components of the MV leaflets; (c) to establish the added diagnostic value of 3D colourDoppler examination to pure 3D morphologic evaluation. 149 consecutive patients with severe DMR underwent complete 3D TTE before surgery and 2D TOE in the operating room. Echocardiographic data obtained by the different techniques were compared with surgical inspection. 3D TTE was feasible in a relatively short time (8 ± 4 min), with good (49%) and optimal (33%) imaging quality in the majority of cases. 3D TTE had significant better overall accuracy compared to 2D TOE (93 and 91%, p < 0.05, respectively). 2D TOE was significantly more specific than 3D TTE in the identification of A3 prolapse (99 vs. 96%). The colourDoppler mode did not improve significantly the accuracy of 3D TTE, albeit it determined a better sensitivity in the detection of A2 prolapse if compared to 2D TOE (95 vs. 85%). 3D TTE with or without colourDoppler is a feasible and useful method in the analysis of MV prolapse; it allows a preoperative and noninvasive description of the pathology as accurate as the 2D TOE.

Association of coronary microvascular dysfunction with restenosis of left anterior descending coronary artery disease treated by percutaneous intervention.

BACKGROUND: Several patients with successful percutaneous coronary interventions (PCIs) show evidence of coronary microvascular dysfunction (CMVD), which can be responsible for persistent positivity of electrocardiographic exercise stress test (EST). In this study, we assessed whether post-PCI CMVD may predict clinical outcome in patients undergoing successful elective PCI of an isolated stenosis of the left anterior descending (LAD) coronary artery. METHODS: We studied 29 patients (age 64±6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the LAD coronary artery who underwent successful PCI with stent implantation. Coronary blood flow (CBF) velocity response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography 24h and 3months after PCI. The primary end-point was a combination of death, admission for acute coronary syndromes (ACS) or target vessel revascularization (TVR). RESULTS: No death or ACS occurred during 36months of follow-up, but TVR was performed in 5 patients (17.2%). CBF response to CPT at 3months after PCI was 1.31±0.2 vs. 1.71±0.4 in patients with or without TVR, respectively (p=0.03), whereas CBF response to adenosine at 3months in these two groups was 1.70±0.3 vs. 2.05±0.4 (p=0.059). CONCLUSIONS: Our data suggest that, in patients with successful PCI of LAD coronary artery stenosis, lower CBF response to the endothelium-dependent vasodilator stimulus CPT is associated with long-term recurrence of restenosis.

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 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.

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.

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.

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.

Differential effects of heart rate reduction by atenolol or ivabradine on peripheral endothelial function in type 2 diabetic patients.

OBJECTIVE: To assess whether reduction of heart rate (HR) has beneficial effects on endothelial function in patients with type 2 diabetes mellitus (T2DM). DESIGN: Randomised, double-blind, placebo-controlled study. SETTING: University hospital. PATIENTS: 66 T2DM patients without overt cardiovascular disease. INTERVENTIONS: Patients were randomised to receive for 4 weeks, in addition to their standard therapy, one of the following treatments: atenolol (25 mg twice daily), ivabradine (5 mg twice daily) or placebo (1 tablet twice daily). MAIN OUTCOME MEASURES: Systemic endothelial function, assessed by flow-mediated dilation (FMD); endothelium-independent vasodilation, assessed by nitrate-mediated dilation (NMD); cardiac autonomic function, assessed by HR variability (HRV). RESULTS: 61 patients completed the study (19, 22 and 20 patients in atenolol, ivabradine and placebo groups, respectively). Compared with baseline, HR was similarly reduced by atenolol (87±13 vs 69±9 bpm) and ivabradine (86±12 to 71±9 bpm), but not by placebo (82±10 vs 81±9 bpm) (p<0.001). FMD improved at follow-up in the atenolol group (4.8±1.7 vs 6.4±1.9%), but not in the ivabradine group (5.2±2.5 vs 4.9±2.2%) and in the placebo group (4.8±1.5 vs 4.7±1.7%) (p<0.01). NMD did not change significantly in any group. HRV parameters did not change in the placebo group; they, instead, consistently increased in the atenolol, whereas a mild increase in SDNNi was only observed in the ivabradine group. A significant correlation was found in the atenolol group between HR and FMD changes (r=-0.48; p=0.04). CONCLUSIONS: Despite a comparable reduction in HR, atenolol, but not ivabradine, improved FMD in T2DM patients suggesting that changes in HR are by themselves unlikely to significantly improve endothelial function.

Upper arm intermittent ischaemia reduces exercise-related increase of platelet reactivity in patients with obstructive coronary artery disease.

OBJECTIVE: To assess whether upper arm ischaemia influences exercise-induced myocardial ischaemia and platelet activation in patients with coronary artery disease (CAD). DESIGN: Crossover study. SETTING: University hospital. PATIENTS: Twenty patients (17 men) of mean±SD age 64±8 years with stable CAD. INTERVENTIONS: Patients underwent two exercise stress tests (ESTs) on two separate days in a randomised manner: (1) a maximal EST only (EST-1); (2) a maximal EST after intermittent upper arm ischaemia (cycles of alternating 5-min inflation and 5-min deflation of a standard blood pressure cuff) (EST-2). Blood samples were obtained to evaluate platelet reactivity. MAIN OUTCOME MEASURES: Platelet reactivity was assessed by flow cytometry at rest and after EST, with and without ADP stimulation, by measuring the percentage of monocyte-platelet aggregates (MPAs) and CD41 platelet expression measured as mean fluorescence intensity. RESULTS: Remote ischaemia had no significant effect on EST-induced myocardial ischaemia. At rest there were no differences before EST-1 and EST-2 in basal MPA (20.7±2.3 vs 20.8±2.4, p=0.56) and CD41 (21.5±2.3 vs 21.3±2.3, p=0.39), and ADP stimulation induced a similar increase in both MPA (+15.2±8.2% vs +14.9±8.4%, p=0.71) and CD41 (+15.7±5.7% vs 13.37±6.9%, p=0.59). While no differences in the increase in MPA and CD41 expression were observed after EST-1 and EST-2, ADP stimulation after EST-2 induced a lower increase in MPA (+18.3±8.1% vs +27.9±9.7%, p<0.001) and CD41 (+18.3±9.2% vs +27.2±12.4%, p<0.001) than after EST-1. CONCLUSION: These results show that, in patients with stable CAD, remote ischaemia induces protection against an exercise-related increase in platelet reactivity.