Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Early healing after treatment of coronary lesions by thin strut everolimus, or thicker strut biolimus eluting bioabsorbable polymer stents: The SORT-OUT VIII OCT study.

AIMS: Early healing after drug-eluting stent (DES) implantation may reduce the risk of stent thrombosis. The aim of this study was to compare patterns of early healing after implantation of the thin strut everolimus-eluting Synergy DES (Boston Scientific) or the biolimus-eluting Biomatix Neoflex DES (Biosensors). METHODS AND RESULTS: A total of 160 patients with the chronic or acute coronary syndrome were randomized 1:1 to Synergy or Biomatrix DES. Optical coherence tomography (OCT) was performed at baseline and at either 1- or 3-month follow-up. The primary endpoint was a coronary stent healing index (CSHI), a weighted index of strut coverage, neointimal hyperplasia, malapposition, and extrastent lumen. A total of 133 cases had OCT follow-up and 119 qualified for matched OCT analysis. The median CSHI score did neither differ significantly between the groups at 1 month: Synergy 8.0 (interquartile range [IQR]: 3.0; 14.0) versus Biomatrix 8.5 (IQR: 4.0; 15.0) (p = 0.47) nor at 3 months: Synergy 6.5 (IQR: 2.0; 13.0) versus Biomatrix 6.0 (IQR: 4.0; 11.0) (p = 0.83). Strut coverage was 84.6% (IQR: 72.0; 97.9) for Synergy versus 77.6% (IQR: 70.1; 90.3) for Biomatrix (p = 0.15) at 1 month and 90.3% (IQR 79.0; 98.8) (Synergy) versus 83.9% (IQR: 77.5; 92.6) (Biomatrix) (p = 0.068) at 3 months. Pooled 1- and 3-month coverage was 88.6% (IQR: 74.4; 98.4) for Synergy compared with 80.7% (IQR: 73.2; 90.8) for Biomatrix (p = 0.02). CONCLUSIONS: The early healing response after treatment with the Synergy or Biomatrix DES did not differ significantly as determined by a healing index. The Synergy DES showed overall better early stent strut coverage.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.

Diabetes and risk of peripheral artery disease in patients undergoing first-time coronary angiography between 2000 and 2012 - a nationwide study.

BACKGROUND: The risk of peripheral artery disease (PAD) in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is an important and inadequately addressed issue. Our aim is to examine the impact of DM on risk of PAD in patients with different degrees of CAD characterized by coronary angiography (CAG). METHODS: Using nationwide registers we identified all patients aged ≥18 years, undergoing first time CAG between 2000 and 2012. Patients were categorized into DM/Non-DM group, and further classified into categories according to the degree of CAD i.e., no-vessel disease, single-vessel disease, double-vessel disease, triple-vessel disease, and diffuse disease. Risk of PAD was estimated by 5-year cumulative-incidence and adjusted multivariable Cox-regression models. RESULTS: We identified 116,491 patients undergoing first-time CAG. Among these, a total of 23.969 (20.58%) had DM. Cumulative-incidence of PAD among DM patients vs. non-DM were 8.8% vs. 4.9% for no-vessel disease, 8.2% vs. 4.8% for single-vessel disease, 10.2% vs. 6.0% for double-vessel disease, 13.0% vs. 8.4% for triple-vessel disease, and 6.8% vs. 6.1% for diffuse disease, respectively. For all patients with DM, the cox-regression analysis yielded significantly higher hazards of PAD compared with non-DM patients with HR 1.70 (no-vessel disease), 1.96 (single-vessel disease), 2.35 (double-vessel disease), 2.87 (triple-vessel disease), and 1.46 (diffuse disease), respectively (interaction-p 0.042). CONCLUSION: DM appears to be associated with increased risk of PAD in patients with and without established CAD, with increasing risk in more extensive CAD. This observation indicates awareness on PAD risk in patients with DM, especially among patients with advanced CAD.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS: In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION: The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING: Biosensors, Aarhus University Hospital, and participating sites.

Invasive angiography and revascularization in patients with stable angina following prior coronary artery bypass grafting: Results from the East Denmark heart registry.

BACKGROUND: There are limited data to guide the optimum approach to patients presenting with angina after coronary artery bypass grafting (CABG). Although often referred for invasive angiography, the effectiveness of this is unknown; angina may also result from diffuse distal or micro-vascular coronary disease and it is not known how often targets for intervention are identified. METHODS: Retrospective review of 50,460 patients undergoing angiography in East Denmark between January 2010 and December 2014. Clinical and procedural data were prospectively stored in a regional electronic database. Follow-up data were available for all patients, by means of records linked to each Danish social security number. RESULTS: In patients with prior CABG and stable angina (n = 2,309), diagnostic angiography led to revascularization in 574 (24.9%) cases. Chronic kidney disease (HR 1.93 [1.08-3.44], P = 0.027), significant angina (HR 1.49 [1.18-1.88], P = 0.006 for angina class ≥ II, and HR 2.04 [1.61-2.58], P < 0.001 for angina class ≥ III) and a positive pre-procedural stress test (HR 2.56 [1.42-4.60], P < 0.001) were independent predictors of revascularization. Stress testing was, however, used less frequently than in patients without prior CABG (17.2% vs. 24.2%, P < 0.001). The positive predictive values for subsequent revascularization were 47.8%, 51.4%, and 66.9% for exercise ECG, stress echocardiography, and myocardial perfusion scintigraphy (MPS), respectively. CONCLUSIONS: Invasive angiography leads to revascularization in a quarter of patients with angina and prior CABG; the threshold for referral may be too low. Non-invasive stress testing predicts the need for revascularization but appears underused and MPS, in particular, may better identify patients likely to require revascularization. © 2016 Wiley Periodicals, Inc.

The potential of optimizing prehospital triage of patients with suspected acute myocardial infarction using high-sensitivity cardiac troponin T and copeptin.

PURPOSE: In patients with a suspected acute myocardial infarction (AMI), to evaluate the potential for early triage based on measurement of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin in blood samples collected in the prehospital phase. MATERIALS AND METHODS: In this retrospective study, we measured hs-cTnT and copeptin in blood samples collected in the ambulance form 962 patients with suspected AMI. The diagnostic accuracy was estimated by receiver-operating characteristic (ROC) curve area under the curve (AUC) for both biomarkers and a combined model. Multivariable Cox regression modelling was used to estimate the predictive value of both biomarkers. RESULTS: In total, 178 (19%) cases had AMI. The AUC for hs-cTnT was 0.81. Adding copeptin increased the AUC to 0.85 (p = 0.004) and the combined model allowed a prehospital rule-out of 45% of cases without AMI (negative predictive value, NPV 98%). Both biomarkers are highly predictive of outcome. CONCLUSIONS: A future application of hs-cTnT and copeptin measurement, performed already in the prehospital phase, could potentially improve the prehospital diagnostic and prognostic classification of patients with a suspected AMI.

Frequency of misdiagnosis in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is characterized by unexplained left ventricle hypertrophy (LVH) ≥15 mm. The condition is often hereditary and family screening is recommended to reduce the risk of adverse disease complications and premature death among relatives. Correct diagnosis of index patients is important to ensure that only relatives at risk of disease development are invited for family screening. PURPOSE: To investigate if patients with ICD-10 codes for HCM (DI421) or hypertrophic obstructive cardiomyopathy (DI422) fulfilled recognised diagnostic criteria. METHODS: All patients with ICD-10 codes for HCM or HOCM at a Department of Cardiology were identified and had their diagnosis validated by a cardiac investigation or a review of their medical records and previous investigations. RESULTS: Two hundred and forty patients had ICD-10 codes for HCM/HOCM, of whom 202 (84%, 202/240) underwent re-examination, while 38 (16%, 38/240) had their hospital notes reviewed. Seventy-six patients (32%, n = 76/240) did not fulfil diagnostic criteria, of whom 39, (51%, n = 39/76) had normal (10 mm) or modest LV wall thickness (11-14 mm). The remaining 37 patients (49%, n = 37/76) had LVH ≥15 mm, which was well-explained by uncontrolled hypertension, (32%, n = 24/76), aortic valve stenosis (19%, n = 7/76) or wild-type amyloidosis (16%, 6/76). CONCLUSION: One-third of patients with ICD-10 codes for HCM or HOCM did not fulfil recognised diagnostic criteria. Incorrect diagnosis of HCM may cause unnecessary family investigations which may be associated with anxiety, and a waste of health care resources. This highlights the need for specialised cardiomyopathy services to ensure correct diagnosis and management of HCM.

Immediate inflammatory response to mechanical circulatory support in a porcine model of severe cardiogenic shock.

BACKGROUND: In selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA. METHODS: Fourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h. Serial blood samples were drawn hourly and analyzed for serum concentrations of interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, and serum amyloid A (SAA). RESULTS: An increase in IL-6, IL-8, and SAA levels was observed during the experiment for both groups. At 2-4 h of support, IL-6 levels were higher in ECMELLA compared to V-A ECMO animals (difference: 1416 pg/ml, 1278 pg/ml, and 1030 pg/ml). SAA levels were higher in ECMELLA animals after 3 and 4 h of support (difference: 401 ng/ml and 524 ng/ml) and a significant treatment-by-time effect of ECMELLA on SAA was identified (p = 0.04). No statistical significant between-group differences were observed in carotid artery blood flow, urine output, and lactate levels. CONCLUSIONS: Left ventricular unloading with Impella during V-A ECMO resulted in a more extensive inflammatory reaction despite similar end-organ perfusion.

Haemodynamic implications of VA-ECMO vs. VA-ECMO plus Impella CP for cardiogenic shock in a large animal model.

AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS). METHODS AND RESULTS: Land-race pigs (weight 70 kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2 < 30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10 mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4 h. CS was induced in 15 pigs (VA-ECMO n = 7, ECMELLA n = 8). At time of CS MAP was <45 mmHg in both groups, with no difference at 4 h (VA-ECMO 64 mmHg ± 11 vs. ECMELLA 55 mmHg ± 21, P = 0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239 mL/min ± 97 vs. 213 mL/min ± 133 (P = 0.6) and 5.2 ± 3.3 vs. 4.2 ± 2.9 mmol/ (P = 0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567 ± 1733 vs. 6921 ± 5036 mmHg × mL/min × 10-3, P = 0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248 mL (179-930) vs. 506 mL (418-2190); P = 0.005]. CONCLUSIONS: In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion.

Three-dimensional multidetector computed tomography versus conventional 2-dimensional transesophageal echocardiography for annular sizing in transcatheter aortic valve replacement: Influence on postprocedural paravalvular aortic regurgitation.

OBJECTIVES: In transcatheter aortic valve replacement (TAVR), the influence of aortic annular assessment with either multidetector computed tomography (MDCT) or conventional transesophageal echocardiography (TEE) on the incidence of postprocedural paravalvular aortic regurgitation (PAR) was evaluated. BACKGROUND: PAR remains a major limitation in TAVR. Appropriate selection of transcatheter heart valve (THV) size is crucial to prevent PAR. METHODS: Outcomes following TAVR with a balloon-expandable THV were compared in two retrospective cohorts identified according to whether THV size selection was based on TEE (study group 1, n = 80) or MDCT (study group 2, n = 58). RESULTS: The two study groups were comparable with regard to baseline clinical, risk score, and echocardiographic characteristics. The incidence of moderate/severe PAR was lower in study group 2 than in group 1, 8.6% versus 28.8% (P < 0.01). The difference between the THV nominal diameter and MDCT annular diameter was predictive of moderate/severe PAR (AUC 0.84; 95% CI: 0.72-0.92). Neither age, gender, body mass index, annular eccentricity index, aortic valve calcification nor the difference between the THV diameter and the TEE annular diameter predicted postprocedural PAR. Increased THV oversizing relative to the MDCT mean annular diameter was associated with reduced severity of PAR. No difference in perprocedural complications between two study groups was observed. CONCLUSION: MDCT-based annular sizing in TAVR significantly reduces postprocedural PAR, and THV oversizing appears pivotal in this aspect. Further delineation of the optimal degree of THV oversizing is needed.

Incidence of myocardial infarction, heart failure, and cardiovascular mortality in patients with peripheral artery disease: trends between 1997 and 2016.

AIMS: Over the past decades, there have been improvements in the management of cardiovascular (CV) disease and risk factors. Long-term contemporary data on the population-level incidence of myocardial infarction (MI), heart failure (HF), and CV mortality in patients with peripheral artery disease (PAD) are sparse, which we aim to investigate in this study. METHODS AND RESULTS: Danish nationwide registers were used to identify all patients aged ≥18 years, with first diagnosis of PAD between 1997 and 2016. Age-standardized incidence rates (IRs) per 1000 person-years were calculated to estimate trends of MI, HF, and CV mortality. The risk of MI, HF, and CV mortality was estimated by 1-year cumulative incidence with death as the competing risk. A total of 131 568 patients with PAD were identified [median age 70.67 (interquartile range, IQR, 61-78) years and 53.05% males]. The IRs showed increasing trends of MI until 2002, with an estimated annual percentage change (APC) of + 0.6 [95% confidence interval (CI) 3.3-16.1, P-value 0.2]. After the year 2002, MI incidence persistently decreased until the study end with an estimated APC of -5.0 (95% CI 3.7-6.3, P < 0.0001), HF declined with an estimated APC of -3.3 (95% CI 2.0-4.6, P < 0.0001); and CV mortality declined, with an APC of -3.5 (95% CI 3.0-4.0, P < 0.0001). CONCLUSION: The incidence of MI (since 2002) and HF in patients with PAD has significantly decreased over time, together with a decline in CV mortality. Our results suggest that preventive strategies have overall improved, most likely due to improvements in the application of guidelines in clinical care.

Patients With Hypertrophic Cardiomyopathy and Normal Genetic Investigations Have Few Affected Relatives.

BACKGROUND: Current guidelines recommend that relatives of index patients with hypertrophic cardiomyopathy (HCM) are offered clinical investigations to identify individuals at risk of adverse disease complications and sudden cardiac death. However, the value of family screening in relatives of index patients with a normal genetic investigation of recognized HCM genes is largely unknown. OBJECTIVES: The purpose of this study was to perform family screening among relatives of HCM index patients with a normal genetic investigation to establish the frequency of familial disease and the clinical characteristics of affected individuals. METHODS: Clinical and genetic investigations were performed in consecutive and unrelated HCM index patients. Relatives of index patients who did not carry pathogenic/likely pathogenic variants in recognized HCM genes were invited for clinical investigations. RESULTS: In total, 60% (270 of 453) of HCM index patients had a normal genetic investigation. A total of 80% of their relatives (751 of 938, median age 44 years) participated in the study. Of these, 5% (34 of 751) were diagnosed with HCM at baseline, whereas 0.3% (2 of 717 [751-34]) developed the condition during 5 years of follow-up. Their median age at diagnosis was 57 years (IQR: 51-70 years). Two-thirds (22 of 36) were diagnosed following family screening, whereas one-third (14 of 36) had been diagnosed previously because of cardiac symptoms, a murmur, or an abnormal electrocardiogram. None of the affected relatives experienced adverse disease complications. The risk of SCD was low. CONCLUSIONS: Systematic family screening of index patients with HCM and normal genetic investigations was associated with a low frequency of affected relatives who appeared to have a favorable prognosis.

Major Cardiac Events in Patients and Relatives With Hereditary Hypertrophic Cardiomyopathy.

Background: Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families. Objectives: The purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes. Methods: A total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants. Results: Forty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up. Conclusions: The disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives.

Stepwise provisional versus systematic culotte for stenting of true coronary bifurcation lesions: five-year follow-up of the multicentre randomised EBC TWO Trial.

BACKGROUND: The multicentre European Bifurcation Club Trial (EBC TWO) showed no significant differences in 12-month clinical outcomes between patients randomised to a provisional stenting strategy or systematic culotte stenting in non-left main true bifurcations. AIMS: This study aimed to investigate the 5-year clinical results of the EBC TWO Trial. METHODS: A total of 200 patients undergoing stent implantation for non-left main bifurcation lesions were recruited into EBC TWO. Inclusion criteria required a side branch diameter ≥2.5 mm and side branch lesion length >5 mm. Five-year follow-up was completed for 197 patients. The primary endpoint was the composite of all-cause mortality, myocardial infarction, or target vessel revascularisation. RESULTS: The mean side branch stent diameter was 2.7±0.3 mm and mean side branch lesion length was 10.3±7.2 mm. At 5-year follow-up, the primary endpoint occurred in 18.4% of provisional and 23.7% of systematic culotte patients (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.41-1.38). No significant differences were identified individually for all-cause mortality (7.8% vs 7.2%, HR 1.11, 95% CI: 0.40-3.05), myocardial infarction (8.7% vs 13.4%, HR 0.64, 95% CI: 0.27-1.50) or target vessel revascularisation (6.8% vs 9.3%, HR 1.12, 95% CI: 0.37-3.34). Stent thrombosis rates were also similar (1.9% vs 3.1%, HR 0.63, 95% CI: 0.11-3.75). There was no significant interaction between the extent of side branch disease and the primary outcome (p=0.34). CONCLUSIONS: In large non-left main true bifurcation lesions, the use of a systematic culotte strategy showed no benefit over provisional stenting for the composite outcome of all-cause mortality, myocardial infarction, or target vessel revascularisation at 5 years. The stepwise provisional approach may be considered preferable for the majority of true coronary bifurcation lesions. CLINICALTRIALS: gov: NCT01560455.

Definitions and Standardized Endpoints for Treatment of Coronary Bifurcations.

The Bifurcation Academic Research Consortium (Bif-ARC) project originated from the need to overcome the paucity of standardization and comparability between studies involving bifurcation coronary lesions. This document is the result of a collaborative effort between academic research organizations and the most renowned interventional cardiology societies focused on bifurcation lesions in Europe, the United States, and Asia. This consensus provides standardized definitions for bifurcation lesions; the criteria to judge the side branch relevance; the procedural, mechanistic, and clinical endpoints for every type of bifurcation study; and the follow-up methods. Considering the complexity of bifurcation lesions and their evaluation, detailed instructions and technical aspects for site and core laboratory analysis of bifurcation lesions are also reported. The recommendations included within this consensus will facilitate pooled analyses and the effective comparison of data in the future, improving the clinical relevance of trials in bifurcation lesions, and the quality of care in this subset of patients.

Randomized comparison of final kissing balloon dilatation versus no final kissing balloon dilatation in patients with coronary bifurcation lesions treated with main vessel stenting: the Nordic-Baltic Bifurcation Study III.

BACKGROUND: It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel (MV) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD. METHODS AND RESULTS: We randomized 477 patients with a bifurcation lesion to FKBD (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major adverse cardiac events: cardiac death, non-procedure-related index lesion myocardial infarction, target lesion revascularization, or stent thrombosis within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5% (P=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary assessment. At 8 months, the rate of binary (re)stenosis in the entire bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (P=0.11), in the MV was 3.1% versus 2.5% (P=0.68), and in the side branch was 7.9% versus 15.4% (P=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0% (P=0.024) in the FKBD and no-FKBD groups, respectively. CONCLUSIONS: MV stenting strategies with and without FKBD were associated with similar clinical outcomes. FKBD reduced angiographic side branch (re)stenosis, especially in patients with true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use of contrast media and shorter procedure and fluoroscopy times. Long-term data on stent thrombosis are needed. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00914199.

Zotarolimus-eluting vs. sirolimus-eluting coronary stents in patients with and without acute coronary syndromes: a SORT OUT III substudy.

OBJECTIVES: To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial. BACKGROUND: Currently, only limited data allow direct comparison of clinical outcomes among patients with acute coronary syndrome treated with a second-generation drug-eluting stent (DES) eluting zotarolimus vs. a first-generation DES eluting sirolimus. METHODS: Patients with acute coronary syndrome (n=1052) were randomized to treatment with zotarolimus-eluting (n=506) or sirolimus-eluting (n=546) stents and followed for 18 months. The primary composite endpoint, major adverse cardiac events (MACE), was defined as a composite of cardiac death, myocardial infarction or target vessel revascularization. RESULTS: Zotarolimus-eluting stent treatment compared to sirolimus-eluting stent treatment was associated with increased rates of MACE (8·7% vs. 5·0%; hazard ratio (HR), 1·78; 95% confidence interval (CI), 1·10-2·88; P=0·02) and TVR (6·8% vs. 3·9%; HR, 1·77; 95% CI, 1·03-3·04; P=0·04), while all-cause death, cardiac death, myocardial infarction and definite stent thrombosis did not differ significantly. In the same trial, stable angina pectoris patients (n=1206) were randomized to zotarolimus-eluting (n=614) and sirolimus-eluting (n=592) stents with similar results. CONCLUSIONS: With and without acute coronary syndromes, patients treated with the sirolimus-eluting stent had better clinical outcomes than those treated with the zotarolimus-eluting stent.

Predicted and Observed Mortality at 10 Years in Patients With Bifurcation Lesions in the SYNTAX Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow-up. OBJECTIVES: The aim of this study was to investigate the impact of bifurcation lesions on individual predicted and observed all-cause 10-year mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. METHODS: In the SYNTAXES (SYNTAX Extended Survival) study, 10-year observed and individual predicted mortality derived from the SYNTAX score 2020 (SS-2020) was compared between patients with ≥1 bifurcation (n = 1,300) and those with no bifurcations (n = 487). RESULTS: Among patients treated with PCI, patients with >1 bifurcation lesion compared with those without bifurcation lesions had a significantly higher risk for all-cause death (19.8% vs 30.1%; HR: 1.55; 95% CI: 1.12-2.14; P = 0.007), whereas following CABG, mortality was similar in patients with and those without bifurcation lesions (23.3% vs 23.0%; HR: 0.81; 95% CI: 0.59-1.12; P = 0.207; Pinteraction = 0.006). In PCI patients, a 2-stent vs a 1-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51; 95% CI: 1.06-2.14; P = 0.021). According to the SS-2020, among those with ≥1 bifurcation, there was equipoise for all-cause mortality between PCI and CABG in 2 quartiles of the population, whereas CABG was superior to PCI in the 2 remaining quartiles. CONCLUSIONS: Bifurcation lesions require special attention from the heart team, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity and calculation of individualized 10-year prognosis using the SS-2020 may therefore be helpful in decision making. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972).

Definitions and Standardized Endpoints for Treatment of Coronary Bifurcations.

The Bifurcation Academic Research Consortium (Bif-ARC) project originated from the need to overcome the paucity of standardization and comparability between studies involving bifurcation coronary lesions. This document is the result of a collaborative effort between academic research organizations and the most renowned interventional cardiology societies focused on bifurcation lesions in Europe, the United States, and Asia. This consensus provides standardized definitions for bifurcation lesions; the criteria to judge the side branch relevance; the procedural, mechanistic, and clinical endpoints for every type of bifurcation study; and the follow-up methods. Considering the complexity of bifurcation lesions and their evaluation, detailed instructions and technical aspects for site and core laboratory analysis of bifurcation lesions are also reported. The recommendations included within this consensus will facilitate pooled analyses and the effective comparison of data in the future, improving the clinical relevance of trials in bifurcation lesions, and the quality of care in this subset of patients.