Independent Predictor Of Cardiac Death Research Articles

Abstract 13060: Nutritional Status is Associated With Cardiac Death in Patients With Chronic Limb-Threatening Ischemia Undergoing Endovascular Intervention

Introduction: Chronic limb-threatening ischemia (CLTI) represents the end-stage manifestation of peripheral artery disease. The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in patients with CLTI. Research Questions: The relationship between cardiac death in patients with CLTI undergoing endovascular intervention (EVT) and malnutrition is unknown. Methods: This retrospective study investigated 200 consecutive patients with CLTI and we individually assessed WIfI clinical stage and nutritional status assessed using Geriatric Nutritional Risk Index (GNRI). We then compared cardiac death after EVT between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated association between baseline characteristics. Results: In 200 consecutive patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. Age was significantly higher in the WIfI stage 3, 4 group [median 75, interquartile range (IQR) 68-82] compared with the WIfI stage 1, 2 group (median 70, IQR 63-79, p=0.004). GNRI was significantly lower in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (median 88, IQR 80-97 vs. median 103, IQR 94-111, p<0.001). Median duration of follow-up was 966 days (IQR, 540-1268 days). Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (p=0.002 by log-rank test). Cox proportional hazard univariate analysis revealed that WIfI stage 3, 4 group [Hazard ratio (HR); 4.22, 95% confidence interval (CI): 1.29-13.72, p = 0.012], GNRI (HR;0.93, 95%CI:0.87-0.97, p=0.002), Hemodialysis (HR;4,67, 95%CI:1.28-16.96, p=0.010), Statin (HR;4,52, 95%CI:1.00-20.43, p=0.022), LVEF (HR;0.96, 95%CI:0.92-0.99, p=0.045) were correlated to cardiac death. Multivariate analysis models adjusted for relevant factors showed GNRI (HR;0.93, 95% CI:0.86-0.99, p=0.019) was significantly associated with cardiac death. Conclusion: GNRI may be a crucial independent predictor for cardiac death in patients with CLTI undergoing EVT.

The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data

BackgroundDespite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. ObjectivesThe aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. MethodsIn a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. ResultsIn total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. ConclusionsIn this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

Prognostic value of summed motion score assessed by gated SPECT myocardial perfusion imaging in patients with dilated cardiomyopathy.

The prognosis of patients with dilated cardiomyopathy (DCM) is poor and new indicators are urgently needed to predict lethal cardiac events. This study aimed to investigate the value of summed motion score (SMS) in predicting cardiac death of DCM patients using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Eighty-one patients with DCM who underwent 99mTc-MIBI gated SPECT MPI were retrospectively enrolled and were divided into cardiac death and survivor groups. The functional parameters of left ventricle including SMS were measured using quantitative gated SPECT software. During the follow-up period of 44 (25, 54) months, 14 (17.28%) cardiac deaths were observed. Compared with the survivor group, SMS was significantly higher in the cardiac death group. Multivariate cox regression analysis showed that SMS was an independent predictor for cardiac death (HR 1.34, 95% CI 1.02-1.77, P = 0.034). SMS also provided incremental prognostic value over other variables in the multivariate model as determined by likelihood ratio global chi-squared test. In the Kaplan-Meier survival analysis, the event-free survival rate was significantly lower in the high-SMS (HSMS) group than the low-SMS (LSMS) (log-rank P < 0.001). Furthermore, the area under curve (AUC) of SMS was larger than that of LVEF at the 12th month of follow-up (0.85 vs. 0.80, P = 0.045). SMS is an independent predictor of cardiac death in DCM patients and provides incremental prognostic value. SMS might have higher predictive value than LVEF for early cardiac death.

737 CLINICAL AND PROGNOSTIC SIGNIFICANCE OF LEFT VENTRICULAR OUTFLOW TRACT VELOCITY TIME INTEGRAL (LVOT-VTI) IN PATIENTS WITH CHRONIC HEART FAILURE

Abstract Background The echocardiographic evaluation of cardiac output relies on the product of the flow across the left ventricular outflow tract (LVOT), estimated through its velocity time integral (LVOT-VTI), and its cross-sectional area, estimated through the formula πr2. Considering the geometrical assumption behind such formula, LVOT-VTI may be a more reproducible surrogate of systolic function and showed prognostic value in the critical care setting. However, the role of this measure in patients with chronic heart failure (HF) remains unexplored. Objective To assess the clinical and prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF. Methods Outpatients with chronic HF with either reduced (≤40%) or mildly reduced (41-49%) LV ejection fraction (LVEF) were prospectively enrolled to undergo a clinical, echocardiographic, and biohumoral assessment, and were followed-up for the endpoint of cardiac death. Results Finally, 971 patients were enrolled (71±12 years, 72% men, 50% ischemic etiology, LVEF 35±9%, 74% HFrEF). Most patients showed a NYHA class I-II (74%) and were treated with ACE-inhibitors/ARBs or ARNI (81%), beta-blockers (95%), and mineralocorticoid receptor antagonists (71%). Patients were distinguished in three subgroups according to LVOT-VTI tertiles, i.e., ≤19 (n=324), 20-24 (n=324), or &amp;gt;24 (n=323). Compared with the other two subgroups, patients with LVOT-VTI ≤19 showed worse NYHA class, lower LVEF and tricuspid annular plane systolic excursion (TAPSE), and higher E/e’, left atrial volume index (LAVi), estimated systolic pulmonary arterial pressure, and NT-proBNP concentration (all p&amp;lt;0.001). No differences were observed as for patients’ age, HF etiology, and therapies (all p&amp;gt;0.05). Over a median follow-up of 22 (9-34) months, 68 (7%) patients met the primary endpoint. LVOT-VTI significantly stratified the risk of cardiac death, observing 44 (13%), 15 (5%), and 9 (3%) events across the subgroups with values ≤19, 20-24, or &amp;gt;24 (log-rank 25.9, p&amp;lt;0.001). At multivariable regression analysis, LVOT-VTI ≤19 (HR 2.32 [95% 1.20-4.49], p=0.002), but not LVEF &amp;lt;30% (p=0.614) was an independent predictor of cardiac death in a model adjusted for age, sex, ischemic etiology, renal function, hemoglobin, E/e’, LAVi, TAPSE, and NT-proBNP. Of note, this finding was consistent both in the HFrEF and HFmrEF subsets (p for interaction =0.899). Conclusion LVOT-VTI is associated with disease severity and is a strong predictor of all-cause death in patients with chronic HF.

Prognostic Impact of Target Lesion Revascularization on Long-Term Cardiac Mortality After Current-Generation Drug-Eluting Stent Implantation for Left Main Distal Bifurcation: the Milan and New-Tokyo (MITO) Registry

BackgroundThere are scarce data about the incidence and impact on clinical outcomes of target lesion revascularization (TLR) after percutaneous coronary intervention (PCI) for unprotected left main distal bifurcation lesions (ULMD) in current generation drug eluting stent (cDES) era. ObjectivesWe evaluated the incidence and impact on clinical outcomes of TLR after PCI using cDES for ULMD. MethodsWe identified 720 patients treated with cDES for ULMD at New Tokyo Hospital (Matsudo, Japan), San Raffaele Scientific Institute and EMO-GVM Centro Cuore Columbus (Milan, Italy) between January 2005 and December 2015. We divided those patients in 2 groups; TLR group (n = 107), no TLR group (n = 613). The TLR group was comprised patients undergoing a repeat revascularization by PCI or coronary artery bypass grafting of the target lesion. Analysis using propensity score adjustment was also performed. The primary endpoint was cardiac mortality. Additionally, we analyzed the impact of TLR for each main branch (MB) or side branch on cardiac mortality using multivariate Cox regression analysis. ResultsCardiac mortality was significantly higher in TLR group than in no TLR group (adjusted HR 1.96; 95 % CI, 1.50–3.62; p = 0.032). Cardiac mortality was also significantly higher in TLR group after propensity score adjustment. TLR for MB was identified as an independent predictor of cardiac death on multivariate Cox regression analysis. ConclusionsThe TLR, especially the TLR for MB, after PCI even with cDES for ULMD, was strongly associated with worse cardiac mortality.

Abstract 10593: Resting Energy Expenditure is an Important Factor to Predict Cardiac Mortality in Chronic Heart Failure

Introduction: Parameters derived from cardiopulmonary exercise testing (CPET) with respiratory gas analyzer are important prognostic factors in patients with chronic heart failure (CHF). However, all patients with CHF cannot undergo CPET for reasons such as frailty and comorbidity. On the other hands, resting energy expenditure (REE) derived from respiratory gas analyzer can be easily measured in most patients with CHF, but clinical significance of this parameter had not been fully elucidated in patients with CHF. Aims: We aimed to determine the clinical importance including the prognostic impact of REE in patients with CHF. Methods: A total of 1185 consecutive CHF patients who underwent CPET were enrolled. REE was calculated by Weir's formula (3.941resting oxygen consumption (VO 2 )+1.106resting carbon dioxide production (VCO 2 )). The study population was divided into two groups according to median REE and we compered the clinical characteristics between two groups. Also, we examined the value of REE to predict cardiac mortality in CHF patients. Results: In all subjects, 966 were males, median age was 63 years. Median resting VO 2 was 236 ml/min, median resting VCO 2 was 222 ml/min and median REE was 1178 kcal/day. Patients with low REE (&lt;1178 kcal/day) were older and had higher prevalence of female and anemia, lower body mass index (BMI), more impaired renal function, lower parameters of nutrition such as serum total protein and albumin, higher levels of plasma type-B natriuretic peptide, lower resting VO 2 , lower resting VCO 2 and lower peak VO 2 than those with high REE (&gt;1178 kcal/day). But left ventricular ejection fraction was similar between two groups. Patients with low REE had significantly higher rates of cardiac death, all cause death and composite cardiac event (cardiac death and re-hospitalization due to worsening heart failure). Furthermore, REE was the independent predictor of cardiac death, all-cause death and composite cardiac events in the Cox proportional hazard analysis after adjusted cofounding variables including peak VO 2 . Conclusions: REE as well as peak VO 2 is important predictor of cardiac mortality in patients with CHF.

Prognostic value of ventricular mechanical dyssynchrony in patients with left ventricular aneurysm: A comparative study of medical and surgical treatment

BackgroundThe prognostic value of left ventricular (LV) mechanical dyssynchrony (MD) in patients with LV aneurysm (LVA) is unclear. This study aimed to investigate the long-term prognostic value of LVMD in LVA patients. Methods92 consecutive patients who underwent 99mTc-sestamibi-gated SPECT myocardial perfusion imaging (GSPECT) were retrospectively analyzed and followed-up for a median of 63 months (range, 1-73 months). LV function and histogram bandwidth (BW) were analyzed by QGS software. LVMD was defined by ROC analysis. Cardiac death was defined as the primary endpoint, and the composite of cardiac deaths and severe or acute heart failure (MACE) as the secondary endpoint. ResultsThe annual cardiac mortality rate of LVA patients with LVMD and treated by surgical therapy was significantly lower than those treated by medical therapy (2.40% vs. 6.40%, P < .05) but not annual MACE rate (6.61% vs. 10.06%, P > .05). In patients without LVMD, no significant difference in survival and MACE-free survival between medical and surgical treatment. In addition, the occurrence of LVMD is related to the worsen cardiac outcome in terms of MACE and cardiac death, independent of the treatment methods. BW was an independent predictor for MACE (HR 1.010, P < .01) and LVEF (HR .928, P < .05) was an independent predictor for cardiac death in all LVA patients. ConclusionsLVA patients with LVMD might be associated with high risk for cardiac death and surgical treatment might improve cardiac survival compared to medical therapy in these patients.

Prognostic value of pulmonary artery pulsatility index in chronic heart failure patients with reduced ejection fraction

Background The co-existence of right ventricular dysfunction (RVD) in heart failure patient with reduced ejection fraction (HFrEF) is an independent maker of poor prognosis. A novel right ventricular hemodynamic composite measure is the pulmonary artery pulsatility index (PAPi), which is the pulmonary artery pressure gradient ratio. It is a strong predictor of RVD in patients with acute inferior myocardial infarction and patients undergoing left ventricular assist device (LVAD) implantation. However, little is known about its prognostic value in patients with HFrEF. Methods Between September 2010 and July 2013, 172 patients with HFrEF admitted to the tertiary hospital were included in this analysis. We carried out a cardiac catheterisation for each patient, at baseline. Subsequently, we evaluated both PAPi and the other hemodynamic parameters with longitudinal follow-up of adverse outcomes such as cardiac mortality, LVAD, and heart transplantation (HTx). Results During a median follow-up period of 52 months we observed 50 cardiac deaths, 12 LVAD implantations and 10 HTx. A threshold for PAPi value of 2.82 was ascertained (Area: 0.76, p < 0.001, CI: 0.67–0.85, sensitivity 67%, specificity 69%). After dividing the study population into two groups, PAPi ≤2.82 and PAPi >2.82, no significant difference was demonstrated with respect to the aetiology of heart failure (ischaemic HFrEF p = 0.29 and non-ischaemic HFrEF p = 0.29). In Cox regression survival analysis, PAPi was an independent predictor of cardiac death (hazard ratio 0.73 [95% confidence interval 0.53–0.99], p = 0.045). Conclusion In patients with HFrEF, a low PAPi value (<2.82) was associated with increased cardiac mortality risk.

Abstract 9577: Resting Energy Expenditure is Important Factor to Predict Cardiac Mortality in Chronic Heart Failure

Introduction: Parameters derived from cardiopulmonary exercise testing (CPX) including peak oxygen consumption (VO 2 ) are important prognostic factors in patients with chronic heart failure (CHF). However, all patients with CHF cannot undergo CPX because of such as exercise intolerance. On the other hands, resting parameters derived from respiratory gas analyzer including resting energy expenditure (REE) could be easily measured and clinical significance of these parameters had not been fully elucidated in patients with CHF. We aimed to determine the prognostic impact of REE in patients with CHF. Methods: A total of 1185 consecutive CHF patients underwent CPX were enrolled. The subjects of this study were divided into two groups according to median REE and we compered the clinical characteristics between two groups. Also, we examined the value of REE (Weir’ formula: 3.941resting VO 2 +1.106resting VCO 2 ) to predict cardiac mortality in CHF patients. Results: In all subjects, 966 were males, median age was 63 years. Median resting VO 2 was 236 ml/min, median resting VCO 2 was 222 ml/min and median REE was 1178 kcal/day. Patients with low REE (&lt;1178 kcal/day) were older and had higher prevalence of female and anemia, lower body mass index (BMI), more impaired renal function, lower parameters of nutrition such as serum total protein and albumin, higher levels of plasma type-B natriuretic peptide, lower resting VO 2 and lower resting VCO 2 and lower peak VO 2 than those with high REE ( &gt; 1178 kcal/day). But left ventricular ejection fraction was similar between two groups. Patients with low REE had significantly higher rates of cardiac death, all cause death and composite cardiac events (cardiac death and re-hospitalization due to worsening heart failure) than those with high REE. Furthermore, REE was the independent predictor of cardiac death, all-cause death and composite cardiac events in the Cox proportional hazard analysis after adjusting for cofounding variables including peak VO 2 . Conclusions: REE as well as peak VO 2 is important predictor of cardiac mortality in patients with CHF.

Diagnostic Value of Angiography-Derived IMR for Coronary Microcirculation and Its Prognostic Implication After PCI.

Background: Angiography-derived index of microcirculatory resistance (angio-IMR) is an emerging pressure-wire-free index to assess coronary microvascular function, but its diagnostic and prognostic value remains to be elucidated.Methods and Results: The study population consisted of three independent cohorts. The internal diagnostic cohort enrolled 53 patients with available hyperemic microcirculatory resistance (HMR) calculated from myocardial blood flow and pressure. The external diagnostic cohort included 35 ischemia and no obstructive coronary artery disease (INOCA) patients and 45 controls. The prognostic cohort included 138 coronary artery disease (CAD) patients who received PCI. Angio-IMR was calculated after the estimation of angiography-derived fractional flow reserve (angio-FFR) using the equation of angio-IMR = estimated hyperemic Pa × angio-FFR × [vessel length/(K × Vdiastole)]. The primary outcome was a composite of cardiac death or readmission due to heart failure at 28 months after index procedure. Angio-IMR demonstrated a moderate correlation with HMR (R = 0.74, p < 0.001) and its diagnostic accuracy, sensitivity, specificity, and area under the curve to diagnose INOCA were 79.8, 83.1, 78.0, and 0.84, respectively, with a best cut-off of 25.1. Among prognostic cohort, patients with angio-IMR ≥25.1 showed a significantly higher risk of cardiac death or readmission due to heart failure than those with an angio-IMR <25.1 (18.6 vs. 5.4%, adjusted HR 9.66, 95% CI 2.04–45.65, p = 0.004). Angio-IMR ≥25.1 was an independent predictor for cardiac death or readmission due to heart failure (HR 11.15, 95% CI 1.76–70.42, p = 0.010).Conclusions: Angio-IMR showed a moderate correlation with HMR and high accuracy to predict microcirculatory dysfunction. Angio-IMR measured after PCI predicts the risk of cardiac death or readmission due to heart failure in patients with CAD.Clinical Trial Registration: Diagnostic and Prognostic Value of Angiography-derived IMR (CHART-MiCro), NCT04825028.

Differential prognostic value of resistin for cardiovascular death in patients with stable coronary artery disease according to the presence of metabolic syndrome

Abstract Background Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in patients with coronary artery disease (CAD). Purpose We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. Methods A total 741 consecutive patients with stable CAD were followed for a median of 5.5 years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death (CD) and secondary hospitalizations for acute coronary syndrome, arrhythmic event or stroke. Results Follow-up data were obtained from 703 patients of whom 79 had a CD (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r=0.159, p&amp;lt;0.001) and IL-6 (r=0.165, p=0.002), and negatively with HDL-cholesterol (r=−0.176, p&amp;lt;0.001). Resistin levels could not predict CD [HR: 1.044; 95% CI: 0.994 to 1.096; p=0.087] neither secondary endpoints [HR: 1.025; 95% CI: 0.983 to 1.068; p=0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independent predictors of CD after adjustment for conventional risk factors and left ventricular ejection fraction (LVEF) [HR: 1.145; 95% CI: 1.057 to 1.240; p=0.001]. Patients with resistin values ≥7.6 ng/mL (median level) had 2.8 times higher risk of CD compared to those with resistin levels &amp;lt;7.6 ng/mL after adjustment for traditional risk factors and LVEF (HR: 2.882; 95% CI: 1.311 to 6.336; p=0.008). Conclusions Resistin is an independent long-term predictor of CD in patients with stable CAD and MS. Funding Acknowledgement Type of funding sources: None. Figure 1

Functional Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI). The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR. The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n=31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n=309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up. In the diagnostic cohort, angio-IMR correlated well with IMR (R=0.778; P< 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR >40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR >40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95%CI: 1.670-5.067; P< 0.001). Angio-IMR >40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95%CI: 1.157-4.079; P=0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index=0.726 vs 0.666 [P< 0.001], net reclassification index=0.704 [P< 0.001]). Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR >40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377).

Homozygosity of the TT methylenetetrahydrofolate reductase C677T genotype is an independent long-term predictor of cardiac death in patients with premature myocardial infarction

Background Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is the main genetic modulator of homocysteine. Data suggest a potential association of homozygosity for the TT MTHFR genotype with premature myocardial infarction (MI). We explored whether TT homozygosity is associated with long-term prognosis in patients with premature ST-segment elevation MI (STEMI). Methods A total of 265 consecutive patients who had survived their first STEMI ≤35 years of age were followed for a median of 8 years (5–12). Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. Serum lipids, homocysteine, folate levels were measured at baseline and all patients were also tested for the MTHFR C677T polymorphism. Results During follow-up 14 patients died (cardiac death) [5.3%] while 84 (31.7%) met the secondary endpoints. In univariate Cox regression analysis TT homozygosity predicted the occurrence of cardiac death (Hazard ratio (HR): 4.071; 95% confidence interval (CI): 1.404–11.809, p = .010) but not the occurrence of secondary endpoints (HR: 0.877; 95% CI: 0.479–1.605, p = .669). TT homozygosity remained an independent predictor of cardiac death after adjustment for conventional risk factors (i.e., sex, diabetes mellitus, hypertension, family history of premature coronary artery disease [CAD]) [HR: 4.350; 95% CI: 1.472–12.856, p = .008]. The association also remained after adjustment for left ventricular ejection fraction or the presence of significant CAD. Conclusions Homozygosity for the TT MTHFR is an independent long-term predictor of cardiac death in patients with premature STEMI.

The Plasma Level of B-Type Natriuretic Peptide is a Useful Predictor of Cardiac Events for Out-Clinic Patients with Asymptomatic Heart Failure

Purpose: The circulating level of B-type Natriuretic Peptide (BNP) is recognized as a biomarker of ventricular dysfunction. In the field of primary prevention, BNP is a useful predictor of cardiac death, heart failure, cerebral infarction, and atrial fibrillation. On the other hand, the predictive value of BNP has not been fully elucidated in patients with coronary artery disease and/or those who are prone to atherosclerosis. Methods: We analyzed 679 patients (average age, 65.3 years; 29.2% women) with asymptomatic heart failure (ACC/AHA stage A to B) undergoing total risk management for cardiovascular disease prevention in the Kitasato Registry for Cardiovascular Disease Prevention. The mean follow-up period was 8.4 years (range, 73–3686 days) for all study patients. Results: Among all patients, 54.0% had coronary artery disease, 54.2% had hypertension, 55.7% had dyslipidemia, 31.2% had diabetes mellitus, and 15.5% had atrial fibrillation. The baseline level of plasma BNP was 47.5 (63.8) [mean (SD)] pg/mL. The plasma BNP level correlated with age and the serum creatinine level. The presence of coronary artery disease or atrial fibrillation significantly affected the plasma level of BNP (P &lt;0.05, P &lt;0.01; respectively). Plasma BNP levels were significantly higher in the event group than in the event-free group [80.4 (123.3) vs. 43.4 (50.8) pg/mL, P &lt;0.0001]. Of all patients, 59 experienced cardiac events and 10 died during the study period. In the multivariate analysis, plasma BNP level, age, and diabetes mellitus were identified as predictive factors. The Cox proportional hazards model showed that the plasma BNP level was an independent predictor of cardiac death. The event-free rate was significantly higher in patients with BNP of 40 pg/mL or less than in those with BNP of 40pg/mL or more. Conclusions: In the present long-term follow-up study, we found that the plasma level of BNP of patients who are in a stable condition was a useful prognostic marker. Circulating levels of plasma BNP could be an independent predictor of cardiac events in patients with asymptomatic heart failure.

Prognostic value of right ventricular mechanical pattern assessed with 3D echocardiography in patients with left-sided heart disease

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the New National Excellence Programme (ÚNKP-19-3-I) of the Ministry for Innovation and Technology in Hungary, and the Artificial Intelligence Research Field Excellence Programme of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary. Background Right ventricular (RV) ejection fraction (EF) has established prognostic significance, which is independent of left ventricular (LV) EF in various cardiac diseases. However, RV EF is a cumulative result of the complex interplay between distinct mechanical components (i.e., shortening along the longitudinal, radial, and anteroposterior directions), and the prognostic value of RV motion decomposition remains to be quantified. Objective Our aim was to explore whether the assessment of longitudinal, radial, and anteroposterior motion components of the RV with 3D transthoracic echocardiography offers prognostic value in patients with left-sided heart disease. Methods Two hundred and ninety-two consecutive patients (age 59 ± 17 years, 70% male) with left-sided heart disease underwent standard clinical investigations and 3D echocardiographic examination. They were followed-up for 6.7 ± 2.2 years, and cardiac death served as the primary endpoint. LV and RV volumes and ejection fractions were quantified by the offline analysis of 3D datasets. The ReVISION method was applied to the 3D models of the RV to decompose the motion along the three orthogonal axes and to calculate longitudinal, radial, and anteroposterior EF (LEF, REF, AEF, respectively). Conventional parameters of RV systolic function (tricuspid annular plane systolic excursion [TAPSE], fractional area change [FAC]) were also assessed. Results Cardiac death occurred in 60 (21%) patients. Patients who died had lower LV EF (39 ± 16 vs. 52 ± 12%, p &amp;lt; 0.001), RV EF (40 ± 11 vs. 48 ± 8%, p &amp;lt; 0.001), and each mechanical component showed significantly lower values compared to patients alive (LEF: 13 ± 6 vs. 19 ± 6%; REF: 22 ± 7 vs. 25 ± 7%; AEF: 14 ± 6 vs. 18 ± 5%, all p &amp;lt; 0.001). LEF was decreased to a greater degree compared to RV EF (relative %: -30 vs. -18). In univariate Cox regression models, RV EF (Hazard Ratio [HR]: 0.928, 95% Confidence Interval [CI] 0.909 – 0.948, p &amp;lt; 0.001), LEF (0.855 [0.816 – 0.896], p &amp;lt; 0.001), REF (0.932 [0.898 – 0.967], p &amp;lt; 0.001), AEF (0.879 [0.841 – 0.919], p &amp;lt; 0.001), TAPSE (0.881 [0.841-0.923], p &amp;lt; 0.001), and FAC (0.955 [0.933-0.977], p &amp;lt; 0.001) were all found to be significant predictors of cardiac death. From all parameters that were predictive, the optimal combination of variables was identified with an automated stepwise selection algorithm. The final multivariate model included serum creatinine (1.015 [1.010 – 1.020], p &amp;lt; 0.001), haemoglobin concentration (0.965 [0.948 – 0.982], p &amp;lt; 0.001), LV EF (0.977 [0.955 – 0.999], p &amp;lt; 0.05), and LEF (0.899 [0.843 – 0.959], p &amp;lt; 0.01) as independent predictors of cardiac death. Notably, the algorithm rather selected LEF and not RV EF. Conclusions 3D echocardiography-derived measurements of RV systolic function are able to predict outcomes in patients with left-sided heart disease independently of LV function. The separate quantification of RV mechanical components can hold additional prognostic value compared to conventional echocardiographic parameters.

Residual systemic inflammatory burden is a major determinant of myocardial recovery and late cardiovascular outcome in Takotsubo patients

Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. 385 patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP < 5.2 mg/l, CRP range 5.2 to 19 mg/l, and CRP > 19 mg/l). The primary endpoint was the impact of RHIR, defined as CRP > 19 mg/l at discharge, on cardiac death or hospitalization for heart failure. Follow-up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge was comparable between groups. By contrast, RHIR was associated with lower LVEF at follow-up (61.7 vs. 60.7 vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.97; 95% confidence interval: 1.11 to 3.49; P = 0.02). RHIR was associated with impaired LVEF recovery and was evidenced as an independent factor of cardiovascular events. All together these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.

Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients.

AimsRecent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS.Methods and resultsPatients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty‐five patients with TTS were split into three subgroups, according to tertiles of C‐reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure.Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025).ConclusionsResidual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high‐risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.

Right ventricular dysfunction by 3D echocardiography is the best predictor for death and re-hospitalization in patients with heart failure with reduced ejection fraction

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), right ventricular (RV) size and dysfunction by 2-dimensional echocardiography (2DE) were identified as risk factors for mortality and morbidity, but 3-dimensional echocardiography (3DE) enabled itself as a more reproducible and accurate method. Aim To assess the comparative prognostic value of parameters of RV size and dysfunction, measured by 2DE and 3DE, in patients with ischemic and non-ischemic HFrEF, on optimal clinical care, at long-term follow-up. Methods 142 consecutive patients (62±12 yrs, 104 males) with HFrEF, in sinus rhythm, were assessed by 2DE and 3DE, including RV full-volume acquisitions. RV diameter (RVd), RV end-systolic (RV_EDA) and end-diastolic areas (RV_ESA), RV fractional area change (RVFAC), and 2D_TAPSE were measured by 2DE. RV end-diastolic (RV_EDV) and end-systolic volumes (RV_ESV), RV ejection fraction (RV_EF), and 3D_TAPSE were measured by a dedicated 3DE software. Patients were followed for 37±16 months after the index event. Primary outcome was cardiac death (CD). Secondary outcomes were: 1) HF hospitalizations (HFH); 2) a composite cardiac events (CE) end-point of CD or HFH, myocardial infarction, coronary revascularization, arrhythmias, or CRT. Results 38 CD, 47 HFH, and 62 CE occurred during follow-up. Mean RVd was 34±7 mm, RV_EDA 20±11 cm2, RV_ESA 12±5 cm2, RV_FAC 37±13%, RV_EDV 84±25 ml/m2, RV_ESV 52±22 ml/m2, and RV_EF 39±10%. Mean 2D_TAPSE was 18±4 mm, while mean 3D_TAPSE was 16±4 mm. By 2DE, only RV_ESA and RV_FAC, but not RV_EDA or RVd, correlated with CD, HFH, and CE. 2D_TAPSE correlated with HFH, but not with CD or CE, while 3D_TAPSE correlated with all primary and secondary outcomes. By 3DE, RV_ESV, but not RV_EDV, correlated with CD, HFH, and CE. Moreover, 3D RV_EF had better correlations with primary and secondary outcomes than 2D RV_FAC (z=3.8, z=2.5, and z=2.5, all p&amp;lt;0.01). By multivariate linear regression analysis including RV_ESA, RV_FAC, RV_ESV, RV_EF, and 3D_TAPSE, only RV_EF was an independent predictor for CD and HFH (r2=0.68 and r2=0.30, both p&amp;lt;0.001). Conclusion In patients with ischemic and non-ischemic HFrEF, 3DE parameters of RV size and dysfunction are better predictors for death and re-hospitalization than 2DE parameters. The RV_EF measured by 3DE was the best predictor for death in patients with HFrEF. Funding Acknowledgement Type of funding source: None

Residual inflammation is a major determinant of myocardial recovery and cardiovascular outcome in takotsubo patients

Abstract Background Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo Syndrome (TTS). Objective In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. 385 patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP&amp;lt;5.2 mg/l, CRP range 5.2 to 19 mg/l, and CRP&amp;gt;19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP&amp;gt;19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Results Follow-up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow-up (61.7 vs. 60.7 vs. 57.9%; p=0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; p=0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.97; 95% confidence interval: 1.11 to 3.49; p=0.02). Conclusions RHIR was associated with impaired LVEF recovery and was evidenced as an independent factor of cardiovascular events. All together these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR. Main results Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): GERCA (Groupe pour l'Enseignement, la prévention et la Recherche Cardiovasculaire en Alsace)

Electromechanical dissociation of left atrium in patients with Cardiac Amyloidosis by Magnetic Resonance: Prognostic and clinical correlates.

ObjectivesLeft atrial (LA) function is an important marker of hemodynamic status in cardiac amyloidosis (CA), and its characterization may provide relevant prognostic information. We sought to assess the prevalence and prognostic impact of LA dysfunction by cardiac magnetic resonance (CMR) in patients with CA.MethodsWe performed CMR in 80 consecutive patients with CA, including 38 with AL (47%) and 42 with ATTR (53%). LA function was assessed by acquiring short axis cine steady-state free precession (SSFP) covering the entire chamber. The atrial emptying fraction (AEF) was calculated as the ratio between the difference of LA maximal and minimal volume to LA maximal volume, expressed as percentage. Severe atrial dysfunction was defined as AEF ≤ 14%.ResultsMean AEF was 18% (13–35%). Overall, AEF ≤ 14% was present in 19 patients (24%), including 21% of those in sinus rhythm (SR) with no history of atrial fibrillation (AF). After a median of 3 years (IQR 2–4), 36 patients (44%) died of cardiac causes. Patients with AEF ≤ 14% showed increased cardiac mortality, with an independent OR of 4.2 (95 IC 2.1–8.2, P < 0.0001). Of note, AEF ≤ 14% was the stronger independent predictor of cardiac death. Patients in SR with AEF ≤ 14% had worse outcome than those with AF.ConclusionsSevere impairment of LA contractile function was present in three-quarters of patients with CA, and was prevalent irrespective of CA etiology, both in the presence and absence of AF. Severe LA dysfunction was associated with an independent 4-fold increase in risk for cardiac death at three years.