Giuseppe Di Gioia

Prognostic value of rest-redistribution tomographic thallium-201 imaging in ischemic cardiomyopathy

The relation between the presence of viable myocardium by rest-redistribution thallium imaging and prognosis is not well defined. This study examined the prognostic value of rest-redistribution single-photon emission computed tomographic imaging with thallium-201 in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Patients were divided into 2 groups: group 1 patients (n = 47) were treated medically and group 2 patients (n = 38) underwent coronary revascularization. The 2 groups were comparable in the extent of CAD and in LV ejection fraction. Thallium images showed normal tracer uptake in 1 group 1 and 3 group 2 patients, fixed defects in 26 group 1 and 18 group 2 patients, and both reversible and fixed defects in 20 group 1 and 17 group 2 patients (p = NS). Based on analysis of 20 segments/patient, reversible defects were seen in 4 +/- 4 segments/patient in group 1 and 5 +/- 5 segments/patient in group 2 (p = NS). Viable myocardium (defined as normal tracer uptake, reversible defects, or mild fixed defects) was seen in 14 +/- 4 segments/patient in group 1 and 15 +/- 5 segments/patient in group 2 (p = NS). During a mean follow-up of 31 months, there were 16 group 1 (34%) and 6 group 2 (16%) deaths. The annual mortality rate was 13% in group 1 and 6% in group 2. Actuarial survival analysis showed better survival in group 2 than in group 1 (p = 0.056). Thus, viable myocardium in patients with CAD and LV dysfunction is associated with poor prognosis with medical therapy. Coronary revascularization improves prognosis.

Prognostic value of tomographic rest-redistribution thallium 201 imaging in medically treated patients with coronary artery disease and left ventricular dysfunction☆☆☆

BackgroundPrevious studies show that rest-redistribution thallium imaging is useful in the assessment of myocardial viability. The impact of such studies on patient outcome is not well defined. This study examined the prognostic value of tomographic rest-redistribution 201TI imaging in 81 medically treated patients with coronary artery disease and left ventricular dysfunction.Methods and ResultsRest-redistribution single-photon emission computed tomographic images were obtained and analyzed quantitatively. The segmental thallium uptake (20 segments per patient) was interpreted as normal, reversible defect, mild to moderate fixed defect, or severe fixed defect. The thallium images were abnormal in 80 patients. The left ventricular ejection fraction was 27%±8% in patients with no redistribution and 26%±7% in patients with redistribution (difference not significant). In patients with no ischemia, there were 7±5 severe fixed defects and 5±4 mild to moderate fixed defects per patient. In patients with ischemia there were 7±4 reversible defects, 3±3 mild to moderate fixed defects, and 5±4 severe fixed defects per patient. The number of any abnormal segments was 11±5 in patients with no ischemia and 14±4 in patients with ischemia (p=0.03). During a mean follow-up of 31±24 months, there were 11 cardiac deaths in patients with no ischemia (26%) and 22 in patients with ischemia (58%); the survival rate was worse in patients with than without ischemia (p<0.05). Multivariate Cox survival analysis on important clinical, angiographic, and thallium variables showed that the presence of redistribution was an independent predictor of death (x2=5; p=0.03).ConclusionsPatients with left ventricular dysfunction and redistribution on rest thallium imaging, a marker of hibernating myocardium, have a higher mortality rate with medical therapy than do patients with a comparable degree of left ventricular dysfunction but with fixed defects only. Thus observations similar to those made with positron emission tomography can be made in a much more straightforward, simple, and probably cost-effective manner with single-photon emission computed tomography.

Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

OBJECTIVES The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. BACKGROUND Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. METHODS In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). RESULTS Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. CONCLUSIONS This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects.

Revascularization decisions in patients with stable angina and intermediate lesions: Results of the international survey on interventional strategy

Background—Fractional flow reserve (FFR) measurement of intermediate coronary stenoses is recommended by guidelines when demonstration of ischemia by noninvasive testing is unavailable. The study aims to evaluate the penetration of this recommendation into current thinking about revascularization strategies for stable coronary artery disease. Methods and Results—International Survey on Interventional Strategy was conducted via a web-based platform. First, participants’ experiences in interventional cardiology were queried. Second, 5 complete angiograms were provided, presenting only focal intermediate stenoses. FFR and quantitative coronary angiography values were known; however, remained undisclosed. Determination of stenosis significance was asked for each lesion. In cases of uncertainty, the most appropriate adjunctive invasive diagnostic method among quantitative coronary angiography, intravascular ultrasound, optical coherence tomography, or FFR needed to be selected. International Survey on Interventional Strategy was taken by 495 participants who provided 4421 lesion evaluations. In 3158 (71%) decisions, participants relied solely on angiographic appearance that was discordant in 47% with the known FFR, using 0.80 as cutoff value. The use of FFR and imaging modalities was requested in 21% and 8%, respectively. Comparing 4 groups of participants according to the experience in FFR, angiogram-based decisions were less frequent with increasing experience (77% versus 72% versus 69% versus 67%, respectively; P<0.001). As a result, requests for FFR were more frequent (14% versus 19% versus 24% versus 28%, respectively; P<0.001) and rates of discordant decisions decreased (51% versus 49% versus 47% versus 43%, respectively; P<0.022). Conclusions—The findings confirm that, even when all potential external constraints are virtually eliminated, visual estimation continues to dominate the treatment decisions for intermediate stenoses, indicative of a worrisome disconnect between recommendations and current practice.

Significance of Intermediate Values of Fractional Flow Reserve in Patients With Coronary Artery Disease.

Background— The fractional flow reserve (FFR) value of 0.75 has been validated against ischemic testing, whereas the FFR value of 0.80 has been widely accepted to guide clinical decision making. However, revascularization when FFR is 0.76 to 0.80, within the so-called gray zone, is still debatable. Methods and Results— From February 1997 to June 2013, all patients with single-segment disease and an FFR value within the gray zone or within the 2 neighboring FFR strata (0.70–0.75 and 0.81–0.85) were included. Study end points consisted of major adverse cardiovascular events (death, myocardial infarction, and any revascularization) up to 5 years. Of 17 380 FFR measurements, 1459 patients were included. Of them, 449 patients were treated with revascularization and 1010 patients were treated with medical therapy. In the gray zone, the major adverse cardiovascular events rate was similar (37 [13.9%] versus 21 [11.2%], respectively; P=0.3) between medical therapy and revascularization, whereas a strong trend toward a higher rate of death or myocardial infarction (25 [9.4] versus 9 [4.8], P=0.06) and overall death (20 [7.5] versus 6 [3.2], P=0.059) was observed in the medical therapy group. Among medical therapy patients, a significant step-up increase in major adverse cardiovascular events rate was observed across the 3 FFR strata, especially with proximal lesion location. In revascularization patients, the major adverse cardiovascular events rate was not different across the 3 FFR strata. Conclusions— FFR in and around the gray zone bears a major prognostic value, especially in proximal lesions. These data confirm that FFR⩽0.80 is valid to guide clinical decision making.

β2-Adrenergic Receptor Stimulation Improves Endothelial Progenitor Cell–Mediated Ischemic Neoangiogenesis

Rationale: Endothelial progenitor cells (EPCs) are present in the systemic circulation and home to sites of ischemic injury where they promote neoangiogenesis. &bgr;2-Adrenergic receptor (&bgr;2AR) plays a critical role in vascular tone regulation and neoangiogenesis. Objective: We aimed to evaluate the role of &bgr;2AR on EPCs’ function. Methods and Results: We firstly performed in vitro analysis showing the expression of &bgr;2AR on EPCs. Stimulation of wild-type EPCs with &bgr;-agonist isoproterenol induced a significant increase of Flk-1 expression on EPCs as assessed by fluorescence-activated cell sorter. Moreover, &bgr;2AR stimulation induced a significant increase of cell proliferation, improved the EPCs migratory activity, and enhanced the EPCs’ ability to promote endothelial cell network formation in vitro. Then, we performed in vivo studies in animals model of hindlimb ischemia. Consistent with our in vitro results, in vivo EPCs’ treatment resulted in an improvement of impaired angiogenic phenotype in &bgr;2AR KO mice after induction of ischemia, whereas no significant amelioration was observed when &bgr;2AR knock out (KO) EPCs were injected. Indeed, wild-type–derived EPCs’ injection resulted in a significantly higher blood flow restoration in ischemic hindlimb and higher capillaries density at histological analysis as compared with not treated or &bgr;2AR KO EPC-treated mice. Conclusions: The present study provides the first evidence that EPCs express a functional &bgr;2AR. Moreover, &bgr;2AR stimulation results in EPCs proliferation, migration, and differentiation, enhancing their angiogenic ability, both in vitro and in vivo, leading to an improved response to ischemic injury in animal models of hindlimb ischemia.

No-Reflow Phenomenon Pathophysiology, Diagnosis, Prevention, and Treatment. A Review of the Current Literature and Future Perspectives

No-reflow is responsible for 40% of the primary percutaneous coronary intervention without complete myocardial reperfusion despite successful reopening of the infarct-related artery. This review describes the main pathophysiological mechanisms of no-reflow, its clinical manifestation, including the strong association with increased in-hospital mortality, malignant arrhythmias, and cardiac failure as well as the diagnostic methods. The latter ranges from simple angiographic thrombolysis in myocardial infarction grade score to more complex angiographic indexes, imaging techniques such as myocardial contrast echo or cardiac magnetic resonance, and surrogate clinical end points such as ST-segment resolution. This review also summarizes the strategies of prevention and treatment of no-reflow, considering the most recent studies results regarding medical therapy and devices.

Prediction of outcome of patients with life-threatening ventricular arrhythmias treated with automatic implantable cardioverter-defibrillators using SPECT perfusion imaging.

BACKGROUND In the present study, we examined the predictors of outcome of 103 patients with coronary artery disease and left ventricular dysfunction who had life-threatening ventricular arrhythmias and were treated with implantable cardioverter-defibrillators with the use of single-photon emission computed tomography (SPECT). METHODS AND RESULTS During a mean follow-up of 29 months, there were 29 cardiac deaths. In comparison with patients who died, survivors had less diabetes mellitus (45% versus 19%, P < .007), higher left ventricular ejection fraction (23 +/- 9% versus 27 +/- 11%, P = .04), and fewer perfusion defects as determined with stress SPECT (15 +/- 5 versus 12 +/- 5, P < .004). Most of the perfusion defects were fixed, indicative of scarring; the extent of reversible defects did not differ (2 +/- 3 in survivors and 3 +/- 4 in nonsurvivors). Multivariate Cox survival analysis identified the number of fixed defects as the only independent predictor of death (chi 2 = 10, P = .002). There were six deaths among 42 patients (14%) with < 8 fixed defects compared with 23 deaths among 61 patients (38%) with > or = 8 defects (P = .005). The 4-year survival was better in patients with < 8 segmental fixed defects than in those with > or = 8 fixed defects (80% versus 36%) (chi 2 = 8, P = .005). CONCLUSIONS The myocardial perfusion pattern is an important determinant of outcome in patients with life-threatening ventricular arrhythmias who are treated with a implantable cardioverter-defibrillator. The extent of scarring separates patients into high- and low-risk groups with a 2.7-fold difference in death rate.

Impact of Right Atrial Pressure on Fractional Flow Reserve Measurements: Comparison of Fractional Flow Reserve and Myocardial Fractional Flow Reserve in 1,600 Coronary Stenoses

OBJECTIVES This study sought to assess the impact of a wide range of mean right atrial pressure (Pra) on fractional flow reserve (FFR) measurements. BACKGROUND FFR invasively assesses the ischemic potential of coronary stenoses. FFR is calculated as the ratio of mean distal coronary pressure (Pd) to mean aortic pressure (Pa) during maximal hyperemia. The Pra is considered to have little impact if it is within normal range, so it is neglected in the formula. METHODS In 1,676 stenoses of 1,235 patients undergoing left-right heart catheterization for ischemic (642 [52%]) or valvular heart disease (593 [48%]), the authors compared the FFR values calculated without accounting for Pra (FFR= Pd/Pa) to the corresponding myocardial fractional flow reserve (FFRmyo) values accounting for Pra (FFRmyo = Pd - Pra/Pa - Pra). RESULTS The median Pra was 7 (interquartile range [IQR]: 5 to 10) mm Hg with a maximum of 27 mm Hg. The correlation and agreement between FFR and FFRmyo was excellent (R(2) = 0.987; slope 1.096 ± 0.003). The median FFR (0.85; IQR: 0.78 to 0.91) was slightly but statistically significantly higher than the median FFRmyo (0.83; IQR: 0.76 to 0.90; p < 0.001) with a median difference of 0.01 (IQR: 0.01 to 0.02). Values of FFR above the cutoff of 0.80 provided an FFRmyo ≤0.80 in 110 (9%) stenoses. No FFR value above 0.80 provided an FFRmyo ≤0.75. CONCLUSIONS The difference between FFR and FFRmyo was minimal even in patients with markedly increased Pra. FFR values above the gray zone (i.e., >0.80) did not yield values below the gray zone (i.e., ≤0.75) in any case, which suggests that the impact of right atrial pressure on FFR measurement is indeed negligible.

Fractional Flow Reserve–Guided Revascularization in Patients With Aortic Stenosis

Fractional flow reserve (FFR) has never been investigated in patients with aortic stenosis (AS). From 2002 to 2010, we identified 106 patients with AS and coronary artery disease with at least one intermediate lesion treated according to FFR guidance. We matched 212 contemporary control patients with AS in which revascularization was decided on angiography only. More patients in the FFR-guided group underwent percutaneous coronary intervention (24% vs 13%; p = 0.019), whereas there was a trend toward less coronary artery bypass grafting (CABG) performed. After FFR, the number of diseased vessels was downgraded within the FFR-guided group (from 1.85 ± 0.97 to 1.48 ± 1; p <0.01) and compared with the angio-guided group (1.48 ± 1 vs 1.8 ± 0.97; p <0.01). Less aortic valve replacement was reported in the FFR-guided group (46% vs 57%; p = 0.056). In patients who underwent CABG, less venous conduits (0.5 ± 0.69 vs 0.73 ± 0.76; p = 0.05) and anastomoses (0.61 ± 0.85 vs 0.94 ± 1; p = 0.032) were necessary in the FFR-guided group. Up to 5 years, we found no difference in major adverse cardiac events (38% vs 39%; p = 0.98), overall death (32% vs 31%; p = 0.68), nonfatal myocardial infarction (2% vs 2%; p = 0.79), and revascularization (8% vs 7%; p = 0.76) between the 2 groups. In conclusion, FFR guidance impacts the management of selected patients with moderate or severe AS and coronary artery disease by resulting into deferral of aortic valve replacement, more patients treated with percutaneous coronary intervention, and in patients treated with CABG, into less venous grafts and anastomoses without increasing adverse event rates up to 5 years.