Antonino Di Franco

Effects of Ivabradine and Ranolazine in Patients With Microvascular Angina Pectoris

Patients with microvascular angina (MVA) often have persistence of symptoms despite full classical anti-ischemic therapy. In this study, we assessed the effect of ivabradine and ranolazine in MVA patients. We randomized 46 patients with stable MVA (effort angina, positive exercise stress test [EST], normal coronary angiography, coronary flow reserve <2.5), who had symptoms inadequately controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily), ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after treatment. Coronary microvascular dilation in response to adenosine and to cold pressor test and peripheral endothelial function (by flow-mediated dilation) were also assessed. Both drugs improved SAQ items and EuroQoL scale compared with placebo (p <0.01 for all), with ranolazine showing some more significant effects compared with ivabradine, on some SAQ items and EuroQoL scale (p <0.05). Time to 1-mm ST-segment depression and EST duration were improved by ranolazine compared with placebo. No effects on coronary microvascular function and on flow-mediated dilation were observed with drugs or placebo. In conclusion, ranolazine and ivabradine may have a therapeutic role in MVA patients with inadequate control of symptoms in combination with usual anti-ischemic therapy.

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.

Three Arterial Grafts Improve Late Survival: A Meta-Analysis of Propensity Matched Studies

Background: Little evidence shows whether a third arterial graft provides superior outcomes compared with the use of 2 arterial grafts in patients undergoing coronary artery bypass grafting. A meta-analysis of all the propensity score-matched observational studies comparing the long-term outcomes of coronary artery bypass grafting with the use of 2-arterial versus 3-arterial grafts was performed. Methods: A literature search was conducted using MEDLINE, EMBASE, and Web of Science to identify relevant articles. Long-term mortality in the propensity score-matched populations was the primary end point. Secondary end points were in-hospital/30-day mortality for the propensity score-matched populations and long-term mortality for the unmatched populations. In the matched population, time-to-event outcome for long-term mortality was extracted as hazard ratios, along with their variance. Statistical pooling of survival (time-to-event) was performed according to a random effect model, computing risk estimates with 95% confidence intervals. Results: Eight propensity score-matched studies reporting on 10 287 matched patients (2-arterial graft: 5346; 3-arterial graft: 4941) were selected for final comparison. The mean follow-up time ranged from 37.2 to 196.8 months. The use of 3 arterial grafts was not statistically associated with early mortality (hazard ratio, 0.93; 95% confidence interval, 0.71–1.22; P=0.62). The use of 3 arterial grafts was associated with statistically significantly lower hazard for late death (hazard ratio, 0.8; 95% confidence interval, 0.75–0.87; P<0.001), irrespective of sex and diabetic mellitus status. This result was qualitatively similar in the unmatched population (hazard ratio, 0.57; 95% confidence interval, 0.33–0.98; P=0.04). Conclusions: The use of a third arterial conduit in patients with coronary artery bypass grafting is not associated with higher operative risk and is associated with superior long-term survival, irrespective of sex and diabetic mellitus status.

Peripheral Arterial Function and Coronary Microvascular Function in Patients with Variant Angina

Objectives: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS). Methods: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively. Results: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography. Conclusions: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation.

Unmeasured Confounders in Observational Studies Comparing Bilateral Versus Single Internal Thoracic Artery for Coronary Artery Bypass Grafting: A Meta‐Analysis

Background Observational studies suggest a survival advantage with bilateral single internal thoracic artery (BITA) versus single internal thoracic artery grafting for coronary surgery, whereas this conclusion is not supported by randomized trials. We hypothesized that this inconsistency is attributed to unmeasured confounders intrinsic to observational studies. To test our hypothesis, we performed a meta‐analysis of the observational literature comparing BITA and single internal thoracic artery, deriving incident rate ratio for mortality at end of follow‐up and at 1 year. We postulated that BITA would not affect 1‐year survival based on the natural history of coronary artery bypass occlusion, so that a difference between groups at 1 year could not be attributed to the intervention. Methods and Results We searched MEDLINE and Pubmed to identify all observational studies comparing the outcome of BITA versus single internal thoracic artery. One‐year and long‐term mortality for BITA and single internal thoracic artery were compared in the propensity‐score–matched (PSM) series, that is, the form of observational evidence less prone to confounders. Thirty‐eight observational studies (174 205 total patients) were selected for final comparison. In the 12 propensity‐score–matched series (34 019 patients), the mortality reduction for BITA was similar at 1 year and at the end of follow‐up (incident rate ratio, 0.70; 95% confidence interval, 0.60–0.82 versus 0.77; 95% confidence interval, 0.70–0.85; P for subgroup difference=0.43). Conclusions Unmeasured confounders, rather than biological superiority, may explain the survival advantage of BITA in observational series.

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.

Endoscopic versus open radial artery harvesting: A meta‐analysis of randomized controlled and propensity matched studies

We sought to investigate the impact of radial artery harvesting techniques on clinical outcomes using a meta‐analytic approach limited to randomized controlled trials and propensity‐matched studies for clinical outcomes, in which graft patency was analyzed.

Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion ImagingCLINICAL PERSPECTIVE

Background—Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown. Methods and Results—The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all P⩽0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes; P<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0; P<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9; P<0.001|2.7±1.0 versus 3.1±1.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (P<0.001) and was associated with each parameter independent of age or medication regimen. Conclusions—Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction.

Open repair of descending thoracic and thoracoabdominal aortic aneurysms in patients with preoperative renal failure

OBJECTIVES To evaluate surgical outcomes in open repair of thoracoabdominal aortic (TAAA) and descending thoracic aortic aneurysms (DTA) in patients with preoperative renal failure (PRF). METHODS Our database was examined for all patients undergoing open TAAA/DTA repair. Patients with a creatinine greater than or equal to 1.5 gm/dl or on haemodialysis were defined as having PRF and were compared to those having normal preoperative renal function. Logistic and Cox regression analysis were used to identify independent determinants of in-hospital outcomes and long-term survival. RESULTS From 1997 to 2015, 711 patients underwent open TAAA/DTA repair. Two hundred and two were categorized as having PRF, of which, 22 where on preoperative haemodialysis. PRF patients had significantly worse comorbidities; smoking (95.5% vs 69.0%; P  < 0.001), chronic pulmonary disease (65.8% vs 29.7%; P  < 0.001), peripheral vascular disease (44.1% vs 19.4%; P  < 0.001) and diabetes (16.3% vs 6.7%; vs P  < 0.001). Operative mortality (OM) was seven-times higher in patients with PRF (14.2 vs 2.2%; P  < 0.001). Logistic regression analysis showed that PRF was a predictor of OM [odds ratio (OR): 4.91; confidence interval (CI): 2.01-11.97; P  < 0.001] and major adverse events (OR: 2.05; CI: 1.21-3.46; P  = 0.007). Kaplan-Meier 5-years survival was significantly lower in PRF patients (45.0% vs 69.8%; P  < 0.001). CONCLUSIONS PRF predicts higher OM and major adverse events incidence following open TAAA/DTA repair. Long-term survival is negatively impacted. Strategies for improving preoperative and intraoperative renal function may lead to better outcomes.

The Radial Artery for Percutaneous Coronary Procedures or Surgery

This article summarizes the current research on the benefits of using the transradial approach for percutaneous procedures and the radial artery as a conduit for coronary artery bypass surgery. Based on the available evidence, the authors provide recommendations for the use of the radial artery in patients undergoing percutaneous or surgical coronary procedures.