Long-term follow-up of patients with chronic total coronary artery occlusion previously randomized to treatment with optimal drug therapy or percutaneous revascularization of chronic total occlusion (COMET-CTO).

Background: The COMET-CTO trial was a randomized prospective study that assessed long-term follow-up in patients with chronic total occlusion (CTO) in coronary arteries treated with percutaneous coronary intervention (PCI) or with optimal medical therapy (OMT). During the 9-month follow-up, the incidence of major adverse cardiac events (MACE) did not differ between the two groups; no death or myocardial infarction (MI) was observed. There was a significant difference in quality of life (QoL), assessed by the Seattle Angina Questionnaire (SAQ), in favor of the PCI group. Here we report long-term follow-up results (56 ± 12 months). Methods: Between October 2015 and May 2017, a total of 100 patients with CTO were randomized into two groups of 50 patients: PCI CTO or OMT group. The primary endpoint of the current study was the incidence of MACE defined as cardiac death, MI, and revascularization [PCI or coronary artery bypass graft (CABG)]. As the secondary exploratory outcome, we analyzed all the cause-mortality rate. Results: Out of 100 randomized patients, 92 were available for long-term follow-up (44 in the PCI group and 48 in the OMT group). The incidence of MACE did not differ significantly between the two groups (p = 0.363). Individual components of MACE were distributed, respectively: cardiac death (OMT vs. PCI group, 6 vs. 3, p = 0.489), MI (OMT vs. PCI group, 1 vs. 0, p = 1), and revascularization (PCI: OMT vs. PCI group, 2 vs. 2, p = 1; CABG: OMT vs. PCI group, 1 vs. 1, p = 1). There was no significant difference between the two groups regarding the individual component of MACE. Six patients died from non-cardiac causes [five deaths were reported in the OMT group and one death in the PCI group (p = 0.206)]. Kaplan-Meier survival curves for MACE did not differ significantly between the study groups (log-rank 0.804, p = 0.370). Regarding the secondary exploratory outcome, a total of 15 patients died at 56 ± 12 months (11 in the OMT and 4 in the PCI group) (p = 0.093). The Kaplan-Meier survival curves for all-cause mortality rates did not differ significantly between the two groups (log rank 3.404, p = 0.065). There were no statistically significant differences between OMT and PCI groups in all five SAQ domains. There was a significant improvement in three SAQ domains in the PCI group: PL (p < 0.001), AF (p = 0.007), and QoL (p = 0.001). Conclusion: After 56 ± 12 months of follow-up, the incidence of MACE, as well as QoL measured by SAQ, did not differ significantly between the PCI and OMT groups.

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

BACKGROUND: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. PURPOSE: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. METHODS: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27-74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10-40 µg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. RESULTS: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967-1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001-0.534; p = 0.019; OR: 1.147; 95% CI: 1.042-1.263; p = 0.005; respectively). CONCLUSIONS: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

Treatment Strategies in Symptomatic Intermediate, Low-Risk, and Asymptomatic Patients With Severe Aortic Stenosis.

Survival of symptomatic patients with severe aortic stenosis (AS) is very poor, with an average mortality reaching up to 2% per month. Approach to diagnosis and treatment of patients with AS was conservative; patients were referred to surgery only if the AS-induced symptoms become apparent and significantly limit the quality of patient' life. In the past 15 years, the novel treatment strategy in subgroups of symptomatic patients with AS have been the subject of extensive research, starting from introduction of transcatheter aortic valve implant (TAVI) in inoperable symptomatic patients with severe AS and continuing further to patients with very high and high operative risk. In the past few years, the focus has further shifted toward the patients with lower operative risk, as well as to asymptomatic patients with severe AS. In the former group, the question relates to whether TAVI is beneficial when compared to SAVR in intermediate- to low-risk patients with symptomatic AS. In the latter group, the main issue is if and when the SAVR should be performed. This article analyzes current status and evidences regarding treatment strategies in symptomatic high, intermediate, low-risk, and asymptomatic patients with isolated severe AS.

Changing concept in treatment of asymptomatic severe aortic stenosis and normal ejection fraction: time for biomarkers reappraisal.

The uncertainty of whether/how to treat asymptomatic patients with isolated severe aortic stenosis and normal left ventricular ejection fraction is one of the most topical in cardiovascular medicine. Recently, the AVATAR trial: first ever randomized trial in the setting of aortic stenosis has been started in an attempt to adequately address this 'burning issue'. In light of this fact it is important to identify biomarkers which might help in risk stratification of these patients, not only in the referring physician's office during a routine exam, but also for preoperative patients scheduled for surgical replacement/transcatheter aortic valve implantation. This report is focusing on novel laboratory parameters which might be helpful in this risk stratification.

The Role of Mitochondrial Dysfunction in Heart Failure and Potential Therapeutic Targets.

Advances in pharmacotherapy as well as device therapy in common cardiovascular diseases, especially implementation of rapid coronary reperfusion as a key management strategy in acute ischemic disease, improved overall survival. Yet, this success contributes to increased number of patients susceptible to heart failure development due to damaged myocardium. Although survival after heart failure diagnosis has improved over time, the death rate remains high: ≈50% of people diagnosed with this disease will die within 5 years. Thus, not only there is a space for novel concepts and strategies in the treatment of symptomatic heart failure, but also they are urgently needed. The mechanisms underlying the development of heart failure are multiple, complex, and not well understood. However, regardless of the cause of heart failure, or whether its presentation is acute or chronic, altered mitochondrial function/bioenergetics appears to play a substantial role in its pathophysiology. As such, the mitochondria are potentially promising, but still underused, target for new HF therapies. This review will focus on changes that occur in the mitochondria of failing myocardium, as well as on targets and approaches that suggest potential therapeutic effect in this ominous disease.

Coronary flow reserve in patients with aortic stenosis and nonobstructed coronary arteries.

OBJECTIVE: Patients with moderate and severe aortic stenosis (AS) and without obstructive epicardial coronary disease have been shown to have an impairment of coronary flow velocity reserve (CFVR). Recently, it has been shown that CFVR is an independent predictor for future cardiovascular events in AS patients. We investigated parameters representing left ventricular (LV) mass and wall thickness, diastolic dysfunction, LV workload and haemodynamic indexes of AS severity to determine which contributes the most to impaired CFVR in patients with AS and a nonobstructed coronary angiogram. METHOD AND RESULTS: A total of 77 patients with moderate or severe AS, mean age 65.66 +/- 11.02 y (57.14% males), were enrolled in this prospective study. All patients had standard Doppler-echo study, coronary angiography and adenosine-stress transthoracic Doppler-echo for CFVR measurement. We took 2.5 as a cut-off value for impaired CFVR. Univariate analysis showed that aortic valve area (AVA), maximal velocity (Vmax), mean pressure gradient (Pmean), energy loss index (ELI), aortic valve resistance (AVR) and stroke work loss (SWL) were associated (P = 0.05) with impaired CFVR. Multivariate analysis showed that AVR was the best predictor of impaired CFVR (RR 0.900, Cl: 0.983-0.997, P = 0.007). Using ROC analysis, the AVR value of 211.22 dynes x s x cm(-5) had the highest accuracy in predicting the impaired CFVR (AUC-0.681, P=0.007, sensitivity 72%, specificity 52%, CI: 0.561-0.800). CONCLUSION: Haemodynamic indices of AS severity, together with LV workload parameters, are the main determinants of CFVR. Among all parameters, AVR is the strongest predictor of CFVR in patients with moderate or severe AS and a nonobstructed coronary angiogram.