Coronary microvascular dysfunction beyond microvascular obstruction in ST-elevation myocardial infarction: Functional and clinical correlates.

OBJECTIVES: To retrospectively characterize clinical predictors and impact on left ventricular (LV) ejection fraction (EF) of microvascular dysfunction (MVD) beyond microvascular obstruction (MVO), in 49 consecutive patients (58 ± 11 years), with successfully treated ST-elevation myocardial infarction. METHODS: By myocardial contrast echocardiography, MVD was considered as myocardial segments with delayed/patchy opacification, while MVO as areas without any opacification. Both MVD and MVO were planimetered and expressed as percentage of total LV wall area. Patients were divided into tertiles of MVO: I (MVO 0%), II (MVO 4-17%), and III (MVO 18-38%) groups. Cardiac troponin T (cTnT) values obtained at admission and at peak were considered for analysis. RESULTS: MVD correlated inversely with EF in groups I and II (p = 0.025, p = 0.019, respectively), but not in group III. MVD was independently predicted by cTnT on admission (ß = 1.85; 95%CI = 0.46-3.24, p = 0.011) and female sex (ß for male sex = -14.46; 95% CI = -27.96-0.95), while MVO by anterior MI (ß = 0.57; 95% CI = 0.26-0.88, p = 0.008) and peak cTnT (ß = 0.97; 95%CI = 0.57-1.38, p < 0.001). Altogether, MVD plus MVO predicted EF (ß = -0.18; 95%CI = -0.28--0.07, p = 0.002). CONCLUSIONS: Even in patients with limited amount of MVO, EF may be impaired by MVD. MVO and MVD have different predictors, which probably reflect their different pathogenesis.

Coronary slow flow is associated with a worse clinical outcome in patients with Takotsubo syndrome.

OBJECTIVE: Patients with Takotsubo syndrome (TTS) present an acute microvascular dysfunction that leads to an impaired myocardial perfusion and, in more severe forms, an impaired epicardial flow. However, clinical relevance of a delayed coronary flow, the coronary slow flow (CSF), has never been investigated. We studied the prognostic value of CSF occurring in the acute phase of TTS. METHODS: This cohort study prospectively evaluated patients with a diagnosis of TTS. CSF was defined as angiographically non-obstructive coronary arteries with thrombolysis in myocardial infarction-2 flow. The incidence of overall mortality and major adverse cardiovascular events (MACEs), defined as the composite of TTS recurrence, cardiac rehospitalisation, cerebrovascular events and mortality, was assessed at follow-up. RESULTS: We enrolled 101 patients (mean age 71.0±11.1 years, 86 (85.1%) female); CSF occurred in 18 (17.8%) patients. At admission, patients with CSF presented more frequently with Killip class III/IV, moderate-to-severe left ventricle systolic dysfunction and right ventricle dysfunction. During the index admission, patients with CSF had a higher rate of intrahospital complications (12 (66.7%) vs 28 (33.7%), p=0.01). At long-term follow-up, patients with CSF had a significantly higher occurrence of overall mortality (9 (50%) vs 19 (22.9%), p=0.011), mainly due to non-cardiac causes (89.3%), and a higher rate of MACE (10 (55.5%) vs 27 (32.5%), p=0.06). At multivariable Cox regression, CSF was independently associated with death from any causes. CONCLUSIONS: Patients with TTS presenting with CSF have a worse clinical presentation with a higher rate of intrahospital complications and a poor long-term clinical outcome.

Fractional flow reserve in acute coronary syndromes and in stable ischemic heart disease: clinical implications.

BACKGROUND: Fractional Flow Reserve (FFR) in Stable Ischemic Heart Disease (SIHD) is universally accepted, while in Acute Coronary Syndromes (ACS) is less established. Aims of this retrospective study were: to compare in patients undergoing FFR assessment the prognostic impact of ACS vs SIHD, to evaluate the clinical relevance of the modality of utilization and timing of FFR assessment and to assess the different outcomes associated with an FFR> or ≤0.80. METHODS: Major cardiac adverse events were assessed at a follow up of 16.4 ±â€¯10.5 months in 543 patients with SIHD and 231 with ACS needing functional evaluation. FFR was used for lesions of ambiguous significance in the absence of a clear culprit vessel (first intention, FI) and for incidental lesions in the presence of a clear culprit vessel (second intention, SI). The decision to perform FFR and the identification of the stenosis needing functional assessment were left to the operator's discretion. Revascularization was performed when FFR was ≤0.80. RESULTS: SIHD and ACS patients were not significantly different for principal clinical characteristics. ACS patients had significantly more events than SIHD, due to an excess of death and myocardial infarction. This was confirmed when FFR was used as FI, in particular if FFR was >0.80. On the contrary, when FFR was used as SI, event rates were similar between ACS and SIHD patients, regardless of FFR value. CONCLUSIONS: Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. This different outcome is confined to those patients in whom FFR is utilized for lesions of ambiguous significance in the absence of a clear culprit vessel.

The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting FFR (MEMENTO-FFR) Study.

AIMS: Adenosine administration is needed for the achievement of maximal hyperaemia fractional flow reserve (FFR) assessment. The objective was to test the accuracy of Pd/Pa ratio registered during submaximal hyperaemia induced by non-ionic contrast medium (contrast FFR [cFFR]) in predicting FFR and comparing it to the performance of resting Pd/Pa in a collaborative registry of 926 patients enrolled in 10 hospitals from four European countries (Italy, Spain, France and Portugal). METHODS AND RESULTS: Resting Pd/Pa, cFFR and FFR were measured in 1,026 coronary stenoses functionally evaluated using commercially available pressure wires. cFFR was obtained after intracoronary injection of contrast medium, while FFR was measured after administration of adenosine. Resting Pd/Pa and cFFR were significantly higher than FFR (0.93±0.05 vs. 0.87±0.08 vs. 0.84±0.08, p<0.001). A strong correlation and a close agreement at Bland-Altman analysis between cFFR and FFR were observed (r=0.90, p<0.001 and 95% CI of disagreement: from -0.042 to 0.11). ROC curve analysis showed an excellent accuracy (89%) of the cFFR cut-off of ≤0.85 in predicting an FFR value ≤0.80 (AUC 0.95 [95% CI: 0.94-0.96]), significantly better than that observed using resting Pd/Pa (AUC: 0.90, 95% CI: 0.88-0.91; p<0.001). A cFFR/FFR hybrid approach showed a significantly lower number of lesions requiring adenosine than a resting Pd/Pa/FFR hybrid approach (22% vs. 44%, p<0.0001). CONCLUSIONS: cFFR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to a minority of stenoses with considerable savings of time and costs.

Three-dimensional quantitative coronary angiography and quantification of jeopardised myocardium to predict functional significance of intermediate coronary artery stenosis.

AIMS: Despite the fact that fractional flow reserve (FFR) is better than angiography in guiding PCI, in the real world the choice to perform PCI is generally based on angiography. Three-dimensional quantitative coronary angiography (3D-QCA) may increase the accuracy of angiography, especially in intermediate coronary artery stenosis (ICAS). The aim of the study was to assess the best cut-off values of area stenosis % (AS%) and the extent of jeopardised myocardium for predicting FFR and for excluding the need to perform FFR. METHODS AND RESULTS: FFR, AS% and Myocardial Jeopardy Index (MJI) were assessed in 211 ICAS. MJI (=-0.36; p=0.001), AS% (=-0.35; p=0.001) and presence of a chronic total occlusion (CTO) (=-0.15; p=0.01) were independent predictors of FFR. In patients without CTO (174 lesions), the best cut-offs for the detection of FFR ≤0.80 for AS% and MJI were 61% (AUC=0.76; p<0.001) and 30% (AUC=0.71; p<0.001), respectively. More importantly, the cut-offs of AS% safely to exclude (100% sensitivity) an FFR ≤0.80 were 40% (AUC=0.85, p<0.001) for an MJI ≥30% and 50% (AUC=0.70, p<0.04) for an MJI <30%, respectively. CONCLUSIONS: AS%, MJI and the presence of a CTO predicted FFR values. 3D-QCA in addition to MJI allows the safe exclusion of FFR ≤0.80, limiting FFR assessment to doubtful cases with considerable reduction of costs.

Cardiac thrombi mistaken for metastasis in recurrent melanoma.

Intra-cardiac thrombi can be incidentally found in recurrent melanoma and need careful assessment. An 81-year-old woman, with a history of malignant nasopharyngeal melanoma, was evaluated by echocardiography and cardiac magnetic resonance due to the detection of undefined masses localized both in right atrium and ventricle during contrast-enhanced thoraco-abdominal computed tomography.

Angiographic assessment of myocardial perfusion in Tako-Tsubo syndrome.

OBJECTIVES: To angiographically assess myocardial perfusion in patients with Tako-Tsubo syndrome (TTS) in comparison with control individuals and patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Coronary microvascular dysfunction has been proposed as the pathophysiological mechanism underlying TTS. METHODS: We retrospectively selected consecutive TTS patients showing typical left ventricular (LV) apical dysfunction admitted to our Department in the period 2007-2011 (n=25). We also enrolled an age and gender-matched control group showing normal coronary arteries (CTR, n=25), patients with STEMI undergoing primary percutaneous intervention with myocardial reperfusion (SR, n=25) or microvascular obstruction (SMVO, n=25). TIMI flow, TIMI frame count (TFC) and both qualitative and quantitative myocardial blush grade in LV apex were assessed. Specifically, myocardial perfusion was quantitatively evaluated using 'Quantitative Blush Evaluator' (QuBE), an open source software previously validated in the setting of STEMI. RESULTS: In TTS, TIMI flow on the LAD was significantly lower and TFC significantly higher compared to CTR and SR (p=0.008 for both), while it did not significantly differ compared to SMVO (p=0.06). In TTS, MBG was significantly lower than that in CTR and SR (p=0.001 for both), while it was significantly higher than that in SMVO (p<0.001). In TTS, QuBE score was significantly lower than that in CTR and SR (p=0.001 for both) and higher than in SMVO (p=0.02). CONCLUSIONS: Our data indicate that myocardial perfusion assessed during angiography is more impaired in patients with TTS than in patients with STEMI exhibiting myocardial reperfusion, while it is less impaired than in patients with STEMI exhibiting MVO.

Usefulness of intracardiac echocardiography for the diagnosis of cardiovascular implantable electronic device-related endocarditis.

OBJECTIVES: The goal of this study was to compare transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) for the diagnosis of cardiac device-related endocarditis (CDI). BACKGROUND: The diagnosis of infective endocarditis (IE) was established by using the modified Duke criteria based mainly on echocardiography and blood culture results. No previous studies have compared ICE with TEE for the diagnosis of IE. METHODS: We prospectively enrolled 162 patients (age 72 ± 11 years; 125 male) who underwent transvenous lead extraction: 152 with CDI and 10 with lead malfunction (control group). Using the modified Duke criteria, we divided the patients with infection into 3 groups: 44 with a "definite" diagnosis of IE (group 1), 52 with a "possible" diagnosis of IE (group 2), and 56 with a "rejected" diagnosis of IE (group 3). TEE and ICE were performed before the procedure. RESULTS: In group 1, ICE identified intracardiac masses (ICM) in all 44 patients; TEE identified ICM in 32 patients (73%). In group 2, 6 patients (11%) had ICE and TEE both positive for ICM, 8 patients (15%) had a negative TEE but a positive ICE, and 38 patients (73%) had ICE and TEE both negative. In group 3, 2 patients (3%) had ICM both at ICE and TEE, 1 patient (2%) had an ICM at ICE and a negative TEE, and 53 patients (95%) had no ICM at ICE and TEE. ICE and TEE were both negative in the control group. CONCLUSIONS: ICE represents a useful technique for the diagnosis of ICM, thus providing improved imaging of right-sided leads and increasing the diagnostic yield compared with TEE.

Effects of late REopening of Coronary total Occlusion on micRovascular perfusion and myocarDial function: the RECORD study.

AIMS: The effects of the reopening of a coronary total occlusion (CoTO) on microvascular perfusion in subacute or chronic coronary syndromes are actually unclear. We aimed at evaluating the microvascular perfusion pattern by myocardial contrast echocardiography (MCE), in addition to contractile function, before and after CoTO reopening. METHODS: Twenty four patients with subacute and chronic coronary syndromes and CoTO datable >7 days underwent evaluation of microvascular perfusion and left ventricular (LV) function by MCE (Acuson Sequoia, with Sonovue, Bracco) before the reopening of the CoTO and at 9 ± 3 months of follow-up. Microvascular perfusion was semi-quantitatively assessed by the contrast score index (CSI), whereas the endocardial length of the perfusion defect [contrast defect length (CDL)], measured in three apical views and averaged, was expressed as a percentage of the total LV endocardial border. The wall motion score index (WMSI), LV volumes, and ejection fraction were also calculated. RESULTS: At baseline, a mild impairment of LV contractile function was observed, which corresponded to a similar impairment of the coronary microvascular perfusion in the overall study population. At follow-up, a significant reduction of CDL% [8.23 (0-19.63) vs. 0 (0-3.68), P = 0.005], improvement of the CSI (1.41 ± 0.29 vs. 1.12 ± 0.17, P = 0.001) and the WMSI (1.73 ± 0.41 vs. 1.33 ± 0.34, P = 0.0004), and increase in the ejection fraction (47.48% ± 8.66 vs. 55.60% ± 8.29, P = 0.0001) were found. CONCLUSION: Reopening of a CoTO in patients with clinical indications to myocardial revascularization is associated with the improvement of coronary microvascular perfusion and the recovery of contractile function.

Positron emission tomography in acute coronary syndromes.

Several imaging techniques have been used to assess cardiac structure and function, to understand pathophysiology, and to guide clinical decision making in the setting of acute coronary syndromes (ACS). Over the last years, cardiac positron emission tomography (PET) has affirmed its role in this setting. Indeed, the combined quantitative assessment of myocardial metabolism and perfusion has allowed to better understand the functional status of infarcted and non-infarcted myocardium, thus improving our knowledge of myocardial response to necrosis. More recently, several studies, taking advantage of previous observations in patients with cancer, have shown that PET could also provide important information on the mechanisms of vascular instability through the early identification of activated inflammatory cells in the atherosclerotic plaque. These findings are opening the way to more effective forms of prevention of acute vascular syndromes in high-risk patients; furthermore, new more sensitive and specific tracers for the identification of vascular inflammation are under development. In this review, we describe the potential and limitations of PET in the assessment of ACS.

Characterization of microvascular and myocardial damage within perfusion defect area at myocardial contrast echocardiography in the subacute phase of myocardial infarction.

AIMS: The anatomical correlates of perfusion defect (PD) at myocardial contrast echocardiography (MCE) in the subacute phase of ST-elevation myocardial infarction (STEMI) are currently unknown. The study aimed at assessing whether, in the subacute phase of STEMI, within MCE PD microvessels are anatomically damaged or if some vasodilation can be still elicited and if the PD correlates with the extent of myocardial necrosis. METHODS AND RESULTS: Twenty-two post-percutaneous coronary intervention (PCI) patients underwent MCE 7 ± 1 days after STEMI, at baseline and after adenosine (ADN) administration. An area of completely non-opacified myocardium, corresponding to the area of the PD, was quantitated by planimetry. The area of the PD on MCE was compared with biochemical and imaging measures of myocardial necrosis: cardiac Troponin T peak (cTnT peak) and hyperenhanced area at gadolinium-enhanced cardiac magnetic resonance (Gd-CMR), respectively. After vasodilator stimulus, the area of the PD remained significantly unchanged when compared with the baseline value (P = 0.09 vs. baseline). The MCE index correlated at baseline with cTnT peak and Gd-CMR assessments of myocardial necrosis (P < 0.001). Also after ADN infusion, correlations between PD and extent of myocardial necrosis were similar to that assessed at baseline. CONCLUSION: When assessed in the subacute phase of STEMI, the extent of the PD on MCE represents an area of both myocardial and microvascular necrosis.

[Focal myocarditis mimicking ST-elevation myocardial infarction in a patient with Helicobacter pylori infection: role of magnetic resonance with late gadolinium enhancement]. / Miocardite simulante un infarto miocardico acuto con sopraslivellamento del tratto ST in paziente con infezione da Helicobacter pylori: ruolo della risonanza magnetica con late gadolinium enhancement.

Myocarditis is an emerging disease. We have investigated a case of focal myocarditis with ventricular thrombus in a patient with Helicobacter pylori infection who came to our attention for the persistence of chest pain one week after previous discharge. The patient was before and otherwise misunderstood as myocardial infarction and recognized in our Centre as myocarditis by magnetic resonance. Diagnostic iter was focused on understanding the pathogenesis of the previous reported cardiac event as well as a link with the persistence of chest pain finally found related to Helicobacter pylori infection. We briefly discuss about role and some caveats of magnetic resonance with late gadolinium enhancement as new diagnostic approach of myocarditis, compared to myocardial biopsy.

Influence of left ventricular hypertrophy on microvascular dysfunction and left ventricular remodelling after acute myocardial infarction.

AIMS: To ascertain whether the presence of left ventricular (LV) hypertrophy in patients with ST-segment elevation myocardial infarction (STEMI) influences microvascular dysfunction and LV remodelling at 6 months of follow-up. METHODS AND RESULTS: Fifty-six consecutive STEMI patients successfully treated with primary or rescue percutaneous coronary intervention underwent conventional two-dimensional and myocardial contrast echocardiography within 24 h and at 6 months. Left ventricular mass, end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction, and wall motion score index (WMSI) were measured. Left ventricular hypertrophy was defined as LV mass index >116 g/m(2) in men and >104 g/m(2) in women. In order to evaluate the potential influence of microvascular dysfunction on LV remodelling, myocardial perfusion was semiquantitatively scored by contrast score index (CSI). Patients with LV hypertrophy had higher EDV and ESV both at 24 h and at 6 months, compared with patients without LV hypertrophy (P < 0.05). No significant changes over time were observed in both groups. Both WMSI and CSI were similar between groups at 24 h and at follow-up, but improved in both groups over time (P < 0.05). CONCLUSION: Left ventricular hypertrophy does not appear to influence the development of post-acute myocardial infarction LV remodelling. Hypertrophic and non-hypertrophic left ventricles showed the same extent and temporal improvement in regional contractile function and microvascular perfusion.

Coronary bifurcation lesions: to stent one branch or both? A meta-analysis of patients treated with drug eluting stents.

BACKGROUND: In the treatment of coronary bifurcation lesions (CBL), with drug eluting stents (DES), we sought to compare angiographic and clinical outcomes of a simple strategy of stenting main vessel only with balloon dilatation of the side branch with a complex strategy of stenting both branches. METHODS: We performed a meta-analysis of six studies, randomized (three) or prospective observational (three), including 963 patients, that directly compared the simple strategy to the complex strategy, in the treatment of CBL with DES. RESULTS: Final minimal lumen diameter (MLD) of the side branch was significantly smaller in the simple strategy group [WMD -0.50 mm, 95% CI (-0.76, -0.24), p<0.00001]. The risk of main vessel restenosis [RR 0.66, 95% CI (0.38-1.17), p=0.16], side branch restenosis [RR 0.62, 95% CI (0.24-1.56), p=0.31], follow up death [RR 0.60, 95% CI (0.19-1.86), p=0.38], follow up myocardial infarction [RR 0.71, 95% CI (0.46-1.10), p=0.13], or target vessel revascularization [RR 0.90, 95% CI (0.56-1.46), p=0.67] was similar between the two strategies. The simple strategy showed a trend to a lower risk of early myocardial infarction [RR 0.65, 95% CI (0.41-1.05), p=0.08]. CONCLUSION: In the treatment of unselected CBL with DES, the complex strategy does not penalize angiographic and clinical outcomes compared to the simple strategy. Further randomized studies are needed to assess the benefit of simple or complex strategy in the treatment of specific subsets of bifurcated lesions.

Prognostic value of heart rate turbulence and its relation to inflammation in patients with unstable angina pectoris.

Heart rate turbulence (HRT) provided insights into cardiac autonomic function and predicted clinical outcome in patients with myocardial infarction. A relation between cardiac autonomic function and inflammation was shown in several clinical settings. To assess the prognostic impact of HRT and its relation with inflammation in patients with unstable angina pectoris (UAP), HRT parameters (turbulence onset [TO] and turbulence slope [TS]) were measured in 331 patients with UAP (age 66.4 +/- 10 years; 231 men) with premature ventricular complexes on electrocardiographic Holter monitoring. Total and cardiac mortality were assessed at the 6-month follow-up. The 6th (-1.52%) and 4th deciles (4.90 ms/RR) were the best prognostic cut-off values for TO and TS, respectively. TS <4.9 ms/RR was associated with hazard ratio (HRs) of 7.10 (95% confidence interval [CI] 2.68 to 18.8, p = 0.0001) and 8.02 (95% CI 2.73 to 23.6, p = 0.0002) for total and cardiac mortality, respectively. The same HRs for TO >-1.52% were 2.94 (95% CI 1.11 to 7.81, p = 0.03) and 3.33 (95% CI 1.13 to 9.79, p = 0.029), respectively. Patients with TO <-1.52% and TS >4.9 ms/RR showed very low risks of total and cardiac mortality (1.8% and 0.9%, respectively). TS <4.9 ms/RR was independently associated with total (HR 3.87, 95% CI 1.21 to 12.3, p = 0.02) and cardiac (HR 3.81, 95% CI 1.01 to 14.4, p = 0.048) mortality at multivariable analyses. Both TS (r = -0.29, p <0.001) and TO (r = 0.16, p = 0.005) showed significant correlation with serum C-reactive protein. Thus, HRT can be helpful for risk stratification of patients with UAP. The association between cardiac autonomic function and inflammation can be pathogenetically relevant in this clinical setting.