The 5 Phenotypes of Tricuspid Regurgitation: Insight From Cluster Analysis of Clinical and Echocardiographic Variables

BackgroundThe recent morphologic classification of tricuspid regurgitation (TR) (ie, atrial functional, ventricular functional, lead related, and primary) does not capture underlying comorbidities and clinical characteristics.ObjectivesThis study aimed to identify the different phenotypes of TR using unsupervised cluster analysis and to determine whether differences in clinical outcomes were associated with these phenotypes.MethodsWe included 13,611 patients with ≥moderate TR from January 2004 to April 2019 in the final analyses. Baseline demographic, clinical, and echocardiographic data were obtained from electronic medical records and echocardiography reports. Ward’s minimum variance method was used to cluster patients based on 38 variables. The analysis of all-cause mortality was performed using the Kaplan-Meier method, and groups were compared using log-rank test.ResultsThe mean age of patients was 72 ± 13 years, and 56% were women. Cluster analysis identified 5 distinct phenotypes: cluster 1 represented “low-risk TR” with less severe TR, a lower prevalence of right ventricular enlargement, atrial fibrillation, and comorbidities; cluster 2 represented “high-risk TR”; and clusters 3, 4, and 5 represented TR associated with lung disease, coronary artery disease, and chronic kidney disease, respectively. Cluster 1 had the lowest mortality followed by clusters 2 (HR: 2.22 [95% CI: 2.1-2.35]; P < 0.0001) and 4 (HR: 2.19 [95% CI: 2.04-2.35]; P < 0.0001); cluster 3 (HR: 2.45 [95% CI: 2.27-2.65]; P < 0.0001); and, lastly, cluster 5 (HR: 3.48 [95% CI: 3.07-3.95]; P < 0.0001).ConclusionsCluster analysis identified 5 distinct novel subgroups of TR with differences in all-cause mortality. This phenotype-based classification improves our understanding of the interaction of comorbidities with this complex valve lesion and can inform clinical decision making.     

Use of fish oil and mortality of patients with cardiometabolic multimorbidity: A prospective study of UK biobank

Background and aimsCardiometabolic multimorbidity (CMM) has risen as a global issue of public health, with an in-creasing prevalence and more severe clinical prognosis. This study aimed to estimate the association between use of fish oil and mortality among patients with CMM.Methods and ResultsIn this prospective study based on UK Biobank, participants with ≥2 of cardiometabolic diseases (CMDs, including coronary heart disease [CHD], diabetes, hypertension, and stroke in this study) at recruitment were included. Use of fish oil was derived from touchscreen questionnaires at baseline. All-cause and cardiovascular mortality were accessed via electronic health-related records. Kaplan–Meier curves and flexible parametric Royston-Parmar proportion-hazard models were fitted to assess the as-sociations of fish-oil use with all-cause, cardiovascular mortality, and related life expectancy alterations. Among 30 068 participants from UK Biobank (67.9% men; mean age 61.75 years), 5357 deaths were reported during 12.03 years of follow-up. For patients with CMM, use of fish oil was associated with a 17% lower risk of all-cause mortality (95% confidence interval [95% CI] 0.78–0.88, P < 0.001), and 19% lower risk of cardiovascular mortality (95% CI 0.72–0.90, P < 0.001) in multivariable-adjusted models. At 45 years old, using fish oil was associated with 1.66 years of life expectancy gained.ConclusionAmong patients with CMM, use of fish oil was associated with a significantly reduced risk of all-cause, cardiovascular mortality, and prolonged life expectancy.     

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China

Background and aimsThe aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM).Methods and resultsA total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405–0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326–0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347–0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205–0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM.ConclusionElevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.     

Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

Early Invasive Strategy Based on the Time of Symptom Onset of Non-ST-Segment Elevation Myocardial Infarction

BackgroundA limitation of the current guidelines regarding the timing of invasive coronary angiography for patients with non–ST-segment elevation acute coronary syndrome is the randomization time. To date, no study has reported the clinical outcomes of invasive strategy timing on the basis of the time of symptom onset.ObjectivesThe aim of this study was to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with non–ST-segment elevation myocardial infarction (NSTEMI).MethodsAmong 13,104 patients from the Korea Acute Myocardial Infarction Registry–National Institutes of Health, 5,856 patients with NSTE myocardial infarction were evaluated. The patients were categorized according to symptom-to-catheter (StC) time (<48 or ≥48 hours). The primary outcome was 3-year all-cause mortality.ResultsOverall, 3,919 patients (66.9%) were classified into the StC time <48 hours group. This group had lower all-cause mortality than the group with StC time ≥48 hours (7.3% vs 13.4%; P < 0.001). The lower risk for all-cause mortality in the group with StC time <48 hours group was consistent in all subgroups. Notably, emergency medical service use (HR: 0.31; 95% CI: 0.19-0.52) showed a lower risk for all-cause mortality than no emergency medical service use (HR: 0.54; 95% CI: 0.46-0.65; P value for interaction = 0.008).ConclusionsAn early invasive strategy on the basis of StC time was associated with a decreased risk for all-cause mortality in patients with NSTEMI. Because the study was based on a prospective registry, the results should be considered hypothesis generating, highlighting the need for further research. (iCReaT Study No. C110016)     

Thrombotic Risk and Cardiovascular Events in Patients With Revascularization Deferral After Fractional Flow Reserve Assessment

ObjectivesThe aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements.BackgroundDeferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time.MethodsFrom J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated.ResultsFFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95% CI: 1.05-1.11; P < 0.001; HTR: HR: 2.16; 95% CI: 1.37-3.39; P < 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95% CI: 1.02-1.06; P < 0.001; HTR: HR: 2.11; 95% CI: 1.56-2.84; P = 0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95% CI: 1.45-3.66; P < 0.001) and MACCE (HR: 2.34; 95% CI: 1.75-3.13; P < 0.001) than those without HTR, even when they had negative FFR.ConclusionsAssessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473)     

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank

BackgroundCardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.ObjectivesThe associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.MethodsNative T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.ResultsHigher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10^-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10^-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10^-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10^-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10^-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).ConclusionsThis large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.     

The interaction between hyperuricemia and low-density lipoprotein cholesterol increases the risk of 1-year post-discharge all-cause mortality in ST-segment elevation myocardial infarction patients

Background and aimsHyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients.Methods and resultsA total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30–5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98–55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30–2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality.ConclusionHyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.     

High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction

Background and aimsTriglyceride glucose (TyG) index is considered a new surrogate marker of insulin resistance that associated with the development of vascular disease. The aim of this study was to evaluate the prognostic value of TyG index in patients with acute myocardial infarction (AMI).Methods and resultsA total of 3181 patients with AMI were included in the analysis. Patients were stratified into 2 groups according to their TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. The incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), p = 0.010], cardiac death [HR (95% CI): 1.68 (1.19,2.38), p = 0.004], revascularization [HR (95% CI): 1.50 (1.16,1.94), p = 0.002], cardiac rehospitalization [HR (95% CI): 1.25 (1.05,1.49), p = 0.012], and composite MACEs [HR (95% CI): 1.19 (1.01,1.41), p = 0.046] in patients with AMI. The independent predictive effect of TyG index on composite MACEs was mainly reflected in the subgroups of male gender and smoker. The area under the curve (AUC) of the TyG index predicting the occurrence of MACEs in AMI patients was 0.602 [95% CI 0.580,0.623; p < 0.001].ConclusionHigh TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.Trial registrationRetrospectively registered.     

10-Year All-Cause Mortality Following Percutaneous or Surgical Revascularization in Patients With Heavy Calcification

ObjectivesThe aim of this study was to assess 10-year all-cause mortality in patients with heavily calcified lesions (HCLs) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).BackgroundLimited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization.MethodsThis substudy of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study assessed 10-year all-cause mortality according to the presence of HCLs within lesions with >50% diameter stenosis and identified during the calculation of the anatomical SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score among 1,800 patients with the 3-vessel disease and/or left main disease randomized to PCI or CABG in the SYNTAX trial. Patients with HCLs were further stratified according to disease type (3-vessel disease or left main disease) and assigned treatment (PCI or CABG).ResultsThe 532 patients with ≥1 HCL had a higher crude mortality rate at 10 years than those without (36.4% vs 22.3%; HR: 1.79; 95% CI: 1.49-2.16; P < 0.001). After adjustment, an HCL remained an independent predictor of 10-year mortality (HR: 1.36; 95% CI: 1.09-1.69; P = 0.006). There was a significant interaction in mortality between treatment effect (PCI and CABG) and the presence or absence of HCLs (P_interaction = 0.005). In patients without HCLs, mortality was significantly higher after PCI than after CABG (26.0% vs 18.8%; HR: 1.44; 95% CI: 0.97-1.41; P = 0.003), whereas in those with HCLs, there was no significant difference (34.0% vs 39.0%; HR: 0.85; 95% CI: 0.64-1.13; P = 0.264).ConclusionsAt 10 years, the presence of an HCL was an independent predictor of mortality, with a similar prognosis following PCI or CABG. Whether HCLs require special consideration when deciding the mode of revascularization beyond their current contribution to the anatomical SYNTAX score deserves further evaluation. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)     

MAFLD is associated with increased all-cause mortality in low cardiovascular-risk individuals but not in intermediate to high-risk individuals

Background and aimsMetabolic-associated fatty liver disease (MAFLD) is increasingly recognized as a systematic disease rather than just a liver disease alone, which raises concerns about its long-term impact on different populations. This study aimed to clarify the effects of MAFLD on long-term outcomes among different cardiovascular risk-stratified populations.Methods and resultsEligible individuals in the Third National Health and Nutrition Examination Surveys (NHANES Ⅲ, 1988–1994) were enrolled. Participants were classified into low, intermediate, or high cardiovascular-risk populations according to the Framingham general equations. Kaplan-Meier survival analysis and Cox regression models were used to investigate the association between MAFLD and long-term outcomes in different cardiovascular-risk populations.A total of 8897 adults were enrolled in the final analysis. The median ages in the non-MAFLD and MAFLD groups were 44 and 49 years old, respectively. During a median follow-up of 22.8 years, a total of 2991 deaths were recorded, including 1694 deaths (30.3%) in non-MAFLD and 1297 deaths (39.2%) in MAFLD (P < 0.001). In the low cardiovascular-risk population, MAFLD individuals had increased all-cause mortality than non-MAFLD individuals (HR = 1.206, 95% CI:1.0338-1.400, P = 0.014). However, similar results were not observed in intermediate or high-cardiovascular-risk individuals. Further analysis of cause-specific mortality suggested that MAFLD was associated with higher cancer-related mortality in the low-risk population (HR = 1.313, 95% CI:1.000-1.725, P = 0.049).ConclusionsMAFLD was associated with increased all-cause mortality among individuals with low cardiovascular risk, rather than those with an intermediate or high cardiovascular risk.     

Platelet Reactivity and Clinical Outcomes After Drug-Eluting Stent Implantation: Results From the PTRG-DES Consortium

BackgroundThe long-term prognostic implication of platelet reactivity after percutaneous coronary intervention (PCI) is not clearly known.ObjectivesThe impacts of platelet reactivity from the PTRG-DES consortium were assessed.MethodsThe primary endpoint was the major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, stent thrombosis, or stroke. Key secondary endpoints were all-cause mortality, major bleeding, and net adverse clinical events (NACE), including MACCE and bleeding.ResultsBetween 2003 and 2018, a total of 11,714 patients were enrolled and grouped into tertiles according to P2Y₁₂ reaction units (PRUs): high PRUs (≥253), intermediate PRUs (188-252), and low PRUs (<188). The Kaplan-Meier (KM) estimates of the primary outcome were significantly different across the groups; the high-PRU group showed the highest MACCE rate at 5 years (12.9%, 11.1%, and 7.0% in high-, intermediate-, and low-PRU groups, respectively; P < 0.001), as well as at 1 year (P < 0.001). The high-PRU group had the greatest KM estimates of all-cause death (8.2%, 5.9%, and 3.7%, respectively; P < 0.001) at 5 years without significant differences of major bleeding, and resultant of a higher KM estimates of NACE (15.7%, 13.6%, and 9.7%, respectively; P < 0.001). A PRU ≥252, the best cutoff value, was strongly related to MACCE (HR: 1.39; 95% CI: 1.11-1.74; P = 0.003) and all-cause death at 5 years after PCI (HR: 1.42; 95% CI: 1.04-1.94; P = 0.026). The optimal cutoff value of aspirin reaction units predicting the MACCE occurrence was ≥414 and was significantly associated with 5-year MACCE occurrence or all-cause death (P < 0.001).ConclusionsIn this large-scale cohort, high PRU was significantly associated with occurrence of MACCE, all-death death, and NACE at 5 years, as well as 1 year after PCI. (PTRG-DES Consortium [PTRG]; NCT04734028)     

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

BackgroundReduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.ObjectivesThis study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.MethodsA total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.ResultsAn increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.ConclusionsGenetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.     

Impact of Nonobstructive Left Main Coronary Artery Atherosclerosis on Long-Term Mortality

BackgroundAlthough the presence of severe stenosis in the left main coronary artery (LMCA) is a well-established predictor of mortality, whether this extends to nonobstructive atherosclerosis in the LMCA is unknown.ObjectivesThe aim of this study was to evaluate the association between LMCA disease by intravascular ultrasound (IVUS) and long-term mortality.MethodsBetween 2005 and 2013, 3,239 patients with LMCA IVUS imaging without LMCA revascularization (either before angiography or scheduled based on index angiography or IVUS) were included. The primary and secondary endpoints were all-cause and cardiac mortality at a minimum of 5 years obtained from the National Death Index.ResultsThe IVUS-measured LMCA minimum lumen area (MLA) and plaque burden were 13.1 ± 5.0 mm² and 41.7% ± 15.6%, respectively. The median follow-up was 8.2 years. The Kaplan-Meier estimated 12-year all-cause and cardiac death rates were 37.5% and 17.0%, respectively. Greater plaque burden (unadjusted HR per 10%: 1.17; 95% CI: 1.12-1.22; P < 0.0001) and smaller IVUS MLA (unadjusted HR per 1 mm²: 0.98; 95% CI: 0.96-0.99; P = 0.0008) were associated with all-cause death. After adjusting for clinical, angiographic, and IVUS factors, plaque burden (adjusted HR per 10%: 1.12; 95% CI: 1.04-1.21; P = 0.003) but not MLA (adjusted HR per 1 mm²: 1.02; 95% CI: 0.99-1.04; P = 0.18) was associated with long-term all-cause death. These findings were also consistent for long-term cardiac mortality.ConclusionsIn the present large-scale study with a 12-year follow-up, increasing LMCA plaque burden was associated with long-term all-cause and cardiac mortality in patients not undergoing LMCA revascularization, even when the lumen area was preserved.     

Comparative Safety of Transcatheter LAAO With the First-Generation Watchman and Next-Generation Watchman FLX Devices

BackgroundProcedural complications limit the clinical benefit of transcatheter left atrial appendage occlusion (LAAO). Next-generation devices incorporate design modifications intended to improve procedural safety, but their clinical impact has not been described.ObjectivesThe aim of this study was to compare in-hospital outcomes for the Watchman FLX with the predicate Watchman 2.5 device.MethodsThe National Cardiovascular Data Registry LAAO Registry was used to identify patients who received the Watchman FLX and an identical number of patients receiving the Watchman 2.5 at the same sites directly preceding the first Watchman FLX case at each site. The primary endpoint was in-hospital major adverse events (MAE), defined as a composite of death, cardiac arrest, stroke, transient ischemic attack, intracranial hemorrhage, systemic arterial embolism, major bleeding, major vascular complication, myocardial infarction, pericardial effusion requiring intervention (percutaneous or surgical), and device embolization. A secondary analysis was performed using 2:1 propensity score matching of patients receiving the Watchman 2.5 or Watchman FLX.ResultsThe study cohort consisted of 27,013 patients receiving each device. The rate of in-hospital MAE was significantly lower for the Watchman FLX compared with the Watchman 2.5 (1.35% vs 2.40%; adjusted OR: 0.57; 95% CI: 0.50-0.65; P < 0.0001), driven largely by fewer pericardial effusions requiring intervention (0.42% vs 1.23%; adjusted OR: 0.34; 95% CI: 0.28-0.42; P < 0.0001). The Watchman FLX was also associated with significant lower rates of the individual endpoints of in-hospital mortality (0.12% vs 0.24%; P < 0.0001), major bleeding (1.08% vs 2.05%; P < 0.0001), cardiac arrest (0.13% vs 0.24%; P = 0.006), and device embolization (0.02% vs 0.06%; P = 0.028), while myocardial infarction, stroke, and major vascular complications did not differ between groups. Propensity score matching analysis demonstrated similar results, with lower rates of MAE with the Watchman FLX (1.34% vs 2.58%; OR: 0.51; 95% CI: 0.46-0.58; P < 0.0001).ConclusionsTranscatheter LAAO with the Watchman FLX was associated with lower rates of in-hospital MAE compared with the predicate Watchman device, including mortality, pericardial effusion, major bleeding, cardiac arrest, and device embolization. This may favorably influence the balance of risks and benefits of transcatheter LAAO for stroke prevention in patients with atrial fibrillation.     

Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium

ObjectivesThis study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD.ResultsDuring the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0.ConclusionsAcross the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.     

Health Status After Transcatheter Tricuspid Valve Repair in Patients With Functional Tricuspid Regurgitation

ObjectivesThe aim of this study was to investigate changes in quality of life (QoL) after transcatheter tricuspid valve repair (TTVR) for tricuspid regurgitation (TR).BackgroundTTVR provides feasible and durable efficacy in reducing TR, but its clinical benefits on QoL still remain unclear.MethodsIn 115 subjects undergoing TTVR for severe functional TR, QoL was evaluated using the 36-Item Short Form Health Survey (SF-36) and the Minnesota Living With Heart Failure Questionnaire (MLHFQ). All-cause mortality, heart failure (HF) rehospitalization, and a composite endpoint of all-cause mortality, HF rehospitalization, and repeat TTVR were recorded as clinical events.ResultsSuccessful device implantation was achieved in 110 patients (96%). Moderate or less TR at discharge was achieved in 95 patients (83%). Mean SF-36 physical component summary (PCS) score improved from 34 ± 9 to 37 ± 9 points (+3 points; 95% CI: 1-5 points; P = 0.001), mean SF-36 mental component summary score improved from 49 ± 9 to 51 ± 10 points (+2 points; 95% CI: 0-4 points; P = 0.017), and mean MLHFQ score decreased from 29 ± 14 to 20 ± 15 points (−8 points; 95% CI: −11 to −5 points; P < 0.001). Baseline PCS, moderate or less TR at discharge, and baseline massive or torrential TR were associated with 1-month change in PCS score (P < 0.05). Change in PCS score after 1 month predicted HF rehospitalization after TTVR (adjusted HR: 0.74 [95% CI: 0.60-0.92] per 5-point increase in PCS score; P = 0.008).ConclusionsThis study demonstrates that TTVR provides improvement in QoL in patients with relevant TR. TR reduction to a moderate or less grade was associated with improvement of SF-36 and MLHFQ scores. Further, global QoL was associated with clinical outcomes and might serve as a future outcome surrogate following TTVR.     

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

BackgroundPercutaneous 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.ObjectivesThe 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.MethodsIn 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).ResultsAmong 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; P_interaction = 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.ConclusionsBifurcation 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)     

Pericoronary Adipose Tissue Attenuation,Low-Attenuation Plaque Burden,and 5-Year Risk of Myocardial Infarction

BackgroundPericoronary adipose tissue (PCAT) attenuation and low-attenuation noncalcified plaque (LAP) burden can both predict outcomes.ObjectivesThis study sought to assess the relative and additive values of PCAT attenuation and LAP to predict future risk of myocardial infarction.MethodsIn a post hoc analysis of the multicenter SCOT-HEART (Scottish Computed Tomography of the Heart) trial, the authors investigated the relationships between the future risk of fatal or nonfatal myocardial infarction and PCAT attenuation measured from coronary computed tomography angiography (CTA) using multivariable Cox regression models including plaque burden, obstructive coronary disease, and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidemia, and family history).ResultsIn 1,697 evaluable participants (age: 58 ± 10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 years. Mean PCAT was ?76 ± 8 HU and median LAP burden was 4.20% (IQR: 0%-6.86%). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (HR: 1.55; P = 0.017, per 1 SD increment) with an optimum threshold of ?70.5 HU (HR: 2.45; P = 0.01). In multivariable analysis, adding PCAT-RCA of ≥?70.5 HU to an LAP burden of >4% (the optimum threshold for future myocardial infarction; HR: 4.87; P < 0.0001) led to improved prediction of future myocardial infarction (HR: 11.7; P < 0.0001). LAP burden showed higher area under the curve compared to PCAT attenuation for the prediction of myocardial infarction (AUC = 0.71 [95% CI: 0.62-0.80] vs AUC = 0.64 [95% CI: 0.54-0.74]; P < 0.001), with increased area under the curve when the 2 metrics are combined (AUC = 0.75 [95% CI: 0.65-0.85]; P = 0.037).ConclusionCoronary CTA–defined LAP burden and PCAT attenuation have marked and complementary predictive value for the risk of fatal or nonfatal myocardial infarction.