REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina.

AIMS: The REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. METHODS: REGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. CONCLUSIONS: This is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Cryoablation for persistent and longstanding persistent atrial fibrillation: results from a multicentre European registry.

AIMS: Although cryoballoon pulmonary vein isolation is a well-established treatment for paroxysmal atrial fibrillation (AF), it's role in persistent AF is unclear. We examined procedural success and long-term outcomes of cryoablation in persistent and longstanding persistent AF. METHODS AND RESULTS: International multicentre registry from three UK and eight European centres. Consecutive patients undergoing cryoablation for persistent AF included. Procedural data, complications, and follow-up were prospectively recorded. Patients were followed-up at 3, 6, and 12 months with an electrocardiogram with open access to arrhythmia nurses thereafter. Ambulatory monitoring was dictated by symptoms. Success was defined as freedom from AF or atrial tachycardia lasting >30 s off antiarrhythmic drugs (AADs). Six hundred and nine consecutive cryoablation procedures. Mean procedure and fluoroscopy times were 95 ± 65 and 13 ± 10 min. Single procedure success rates were 368/602 (61%) off AADs over a median of 2.4 (1.0-4.0) years. Arrhythmia-free survival off AADs was 64% and 57% for persistent and longstanding persistent AF at 24 months of follow-up (P = 0.02). Rate of repeat ablations was 20% in persistent and 32% in longstanding persistent AF (P = 0.006). Cox regression analyses showed a significant association between duration of AF and left atrial diameter and arrhythmia recurrence [hazard ratio (HR) 1.05, P-value 0.01 and HR 1.02, P-value 0.004]. CONCLUSION: Cryoablation for persistent AF is safe, fast and has good outcomes at long-term follow-up. Cryoablation is reasonable as a first line option for these patients. Short procedure times may help increase capacity of cardiac units to meet the rising demand for AF ablation. Randomised control trials are needed to compare outcomes with different techniques.

Routine aspiration thrombectomy is associated with increased stroke rates during primary percutaneous coronary intervention for myocardial infarction.

BACKGROUND: Recent studies have suggested that the routine use of aspiration thrombectomy catheters during primary percutaneous coronary intervention (PCI) do not result in improved mortality and may be associated with an increased stroke rate. This study sought to investigate this hypothesis. METHODS: This was an observational study analysing data from a prospective database of 6366 patients undergoing primary PCI between August 2003 and May 2015 at a UK cardiac centre. Patients' details were collected from the hospital electronic database. Primary outcome was thirty-day stroke rates. RESULTS: 3989 (62.7%) patients underwent PCI alone and 2,377 (37.3%) patients underwent PCI with adjuctive thrombus aspiration. PCI alone group had an older demographic (63 (± 14) years vs 60.7 (± 14)), a lower proportion of male participants 75% vs 79% (P=0.001) and cardiovascular risk factors such as hypertension 22.4% vs 25.3% (P=0.007), hypercholesterolemia 18.5% vs 22.6% (P<0.0001) and a history of smoking 33.5% vs 44.3% (P<0.0001). Thrombus aspiration was associated with a higher 30-day stroke rate [16 (0.7%) vs 11 (0.3%) (HR 2.51; 95% CI 1.03-6.08, P 0.03). Multivariate analysis suggested that this increased risk of stroke was maintained following adjustment for confounders (HR: 1.86; 95% CI 1.02-4.38). There was 379 deaths of which 114 (4.8%) were in the thrombus aspiration cohort vs 265 (6.6%) in PCI only cohort over the follow-up period (60 months). This resulted in a significantly lower rate of all-cause-mortality HR 0.70 (95% CI 0.52-0.94; P 0.02). There was no statistically significant difference in observed myocardial infarction rates HR 0.76 (95% CI 0.47-1.23; P 0.27) and the rates of unscheduled revascularisations HR 0.70 (95% CI 0.43-1.13; P 0.14) between the two groups. CONCLUSIONS: Our data series of STEMI patients, suggest that routine thrombus aspiration during primary PCI is associated with a significantly higher stroke, rate however, thrombus aspiration reduced mortality rate. This is consistent with current guidelines which don't recommend the routine use of thrombus aspiration for primary PCI. A possible mortality reduction in patients with high thrombus grades was seen which may warrant further study.

Angiography-guided Multivessel Percutaneous Coronary Intervention Versus Ischemia-guided Percutaneous Coronary Intervention Versus Medical Therapy in the Management of Significant Disease in Non-Infarct-related Arteries in ST-Elevation Myocardial Infarction Patients With Multivessel Coronary Disease.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) patients with multivessel (MV) disease, after primary percutaneous coronary intervention (PCI), emerging evidence suggests that significant disease in non-infarct-related coronary arteries (IRAs) should be routinely stented. Whether this procedure should be guided by angiography alone or ischemia testing is unclear. METHODS: All STEMI patients treated with primary PCI between January 1, 2005, and December 31, 2012, at a tertiary cardiology center were reviewed retrospectively. Inclusion criterion is patients with at least 70% stenosis in non-IRAs. There were 3 treatment groups: (1) angiography-guided MV-PCI, (2) ischemia-guided PCI, and (3) medical therapy. Primary endpoint is all-cause mortality, and secondary end point is major adverse cardiovascular events (MACE), including death, acute coronary syndrome, revascularization, or stent thrombosis. Event-free survivals were compared using multivariate Cox proportional-hazards analysis. A propensity score-adjusted analysis was performed. RESULTS: Four hundred forty-seven STEMI patients had >70% stenosis in non-IRAs. For all-cause mortality, the 3 strategies did not differ. For MACE, ischemia-guided PCI was associated with the lowest MACE rate, followed by angiography-guided PCI and medical therapy, which was associated with the highest MACE rate, driven by death and myocardial infarction. Hazard ratios (HRs) for MACE: angiography-guided MV-PCI versus ischemia-guided MV-PCI: HR = 2.23 [95% confidence interval (CI), 1.11-4.48; P = 0.023]; medical therapy versus angiography-guided MV-PCI: HR = 1.58 (95% CI, 0.99-2.63; P = 0.062); medical therapy versus ischemia-guided MV-PCI: HR = 1.72 (95% CI, 1.08-2.74; P = 0.022). Propensity score-adjusted analysis yielded similar results. CONCLUSIONS: After primary PCI, complete revascularization in STEMI multivessel disease is associated with lower MACE rates than medical therapy. However, ischemia-testing-guided rather than angiography-guided revascularization was associated with the lowest MACE. This study provides preliminary data and hypotheses for future randomized controlled studies.

Prognostic significance of exercise-induced premature ventricular complexes: a systematic review and meta-analysis of observational studies.

BACKGROUND: Exercise-induced premature ventricular complexes (EI-PVCs) are common during exercise stress tests. Their optimal management and prognostic significance remain uncertain. AIM: To perform meta-analysis of observational studies on the prognostic significance of EI-PVCs. METHODS: A search was conducted on Medline and Embase. Inclusion criteria were observational studies comparing the prognosis of patients with and without EI-PVCs whilst exclusion criteria were studies without confounder adjustment and studies with zero endpoints. Composite endpoints included all-cause mortality, cardiac mortality and cardiovascular events. Relative risk of endpoints were analysed with random effects model. Meta-regression and sensitivity analysis were performed. RESULTS: Ten studies were included. In asymptomatic patients who had no clinical evidence of heart disease, EI-PVCs were associated with a pooled risk ratio of 1.82 (95% CI 1.44 to 2.30) of developing adverse cardiovascular events over 16 years. The corresponding pooled RR for patients with symptomatic heart disease was 1.36 (95% CI 1.18 to 1.57) over 5.4 years. Sensitivity analysis: only EI-PVCs on the recovery phase of an exercise test, not during exercise, had adverse prognostic significance. CONCLUSIONS: EI-PVCs are correlated with a higher risk of all cause death or cardiovascular events in the long term. This risk is elevated in asymptomatic patients without clinical heart disease and in patients with symptomatic heart disease. The fact that only EI-PVCs during recovery, and not during exercise, have poor prognostic value suggests that autonomic dysfunction may play a role in this association. Further studies are needed to see if autonomic manipulation by drugs or catheter-based methods can improve the poor prognosis associated with EI-PVCs.

A 72-year-old male with recurrent syncope.

CLINICAL INTRODUCTION: A 72-year-old patient presented with recurrent syncope 1 year after a myocardial infarction. Two recent falls resulted in fractures to the femur. Serial troponins were negative and ECG demonstrated fixed inferior ST-segment elevation and pathological Q waves. A Holter monitor recorded non-sustained ventricular tachycardia. A subsequent echocardiogram was abnormal, and further investigation with a three-dimensional (3D) cardiac CT coronary angiogram was performed (figure 1). QUESTION: What is the most likely diagnosis? Cardiac tumourHypertrophic obstructive cardiomyopathyVentricular aneurysmVentricular diverticulum heartjnl;103/10/800/HEARTJNL2016309670F1F1HEARTJNL2016309670F1Figure 1Cardiac CT coronary angiogram-three-dimensional reconstruction.