The long-term prognostic value of E/e’ in patients with ST segment elevation myocardial infarction

ObjectivesThis study aimed to evaluate the long-term prognostic value of E/e’ ratio in patients with ST-segment elevation myocardial infarction (STEMI).MethodsWe retrospectively assessed 314 patients who underwent primary coronary interventions between January 2010 and December 2015. The included patients were classified into two groups according to the E/e’ ratios: E/e’<15 (n = 245) and E/e’≥15 (n = 69). We investigated the incidence of major adverse cardiac events (MACEs) from the event to the final follow-up period of at least three years.ResultsA total of 55 cases of MACEs occurred during the follow-up. The E/e’≥15 group showed a significantly higher rate of MACEs than the E/e’<15 group (34.8% vs. 12.7%, p < 0.001). Among the MACE, the percentage of cardiac deaths (17.4% vs. 0.4%, p < 0.001) was higher in the E/e’≥15 group than in the E/e’<15 group. In the multivariable model, E/e’≥15 was demonstrated as the strongest prognostic factor for MACEs (hazard ratio [HR], 2.597; 95% confidence interval [CI], 1.294–5.211; p = 0.007) and cardiac death (HR, 27.537; 95% CI, 3.287–230.689; p = 0.002), while left ventricular ejection fraction (LVEF) was not. Neither the discrepancy of systolic nor diastolic function between initial and follow-up echocardiography affected the overall prevalence of MACEs. A disparity was observed between the two groups, with a significant increase in the rate of MACEs in the E/e’≥15 group (log-rank test, p < 0.001).ConclusionThe baseline E/e’≥15 in patients with STEMI after successful reperfusion is the strongest predictor of poor long-term clinical outcomes among those analyzed.     

Multivessel Versus Culprit-Vessel Percutaneous Coronary Intervention in Patients With Non–ST-Segment Elevation Myocardial Infarction and Cardiogenic Shock

ObjectivesThe aim of this study was to compare in-hospital outcomes and long-term mortality of multivessel versus culprit vessel–only percutaneous coronary intervention (PCI) in patients with non–ST-segment elevation myocardial infarction (NSTEMI), multivessel disease (MVD) and cardiogenic shock.BackgroundThe clinical benefits of complete revascularization in patients with NSTEMI, MVD, and cardiogenic shock remain uncertain.MethodsAmong 25,324 patients included in the National Cardiovascular Data Registry CathPCI Registry from July 2009 to March 2018, the rates of in-hospital procedural outcomes were compared between those undergoing multivessel PCI and those undergoing culprit vessel–only PCI after 1:1 propensity score matching. Among patients aged ≥65 years matched to the Centers for Medicare and Medicaid Services database, long-term mortality was compared using proportional hazards analysis.ResultsMultivessel PCI was performed in 9,791 patients (38.7%), which increased from 32.2% in 2010 to 44.2% in 2017 (p for trend <0.001). After 1:1 propensity matching (n = 7,864 in each group), those undergoing multivessel PCI had a 3.5% (95% confidence interval [CI]: 2.0% to 5.0%) lower absolute rate of in-hospital mortality (30.9% vs. 34.4%; p < 0.001; odds ratio [OR]: 0.85; 95% CI: 0.80 to 0.91), but a higher risk for bleeding (13.2% vs. 10.8%; p < 0.001; OR: 1.26; 95% CI: 1.15 to 1.40) and new requirement for dialysis (5.7% vs. 4.6%; p = 0.001; OR: 1.26; 95% CI: 1.10 to 1.46). Among those surviving to discharge, all-cause mortality was similar through 7 years (conditional hazard ratio: 0.95; 95% CI: 0.87 to 1.03; p = 0.20).ConclusionsNearly 40% of patients with NSTEMI with MVD and cardiogenic shock underwent multivessel PCI, which was associated with lower in-hospital mortality but greater peri-procedural complications. Among those surviving to discharge, multivessel PCI did not confer additional long-term mortality benefit.     

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

ObjectivesThis study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis.BackgroundThe prognostic value of stress dynamic CTP with CTDE is unknown.MethodsParticipants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE.ResultsDuring a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001).ConclusionsStress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.     

Deep-Learning Models for the Echocardiographic Assessment of Diastolic Dysfunction

ObjectivesThe authors explored a deep neural network (DeepNN) model that integrates multidimensional echocardiographic data to identify distinct patient subgroups with heart failure with preserved ejection fraction (HFpEF).BackgroundThe clinical algorithms for phenotyping the severity of diastolic dysfunction in HFpEF remain imprecise.MethodsThe authors developed a DeepNN model to predict high- and low-risk phenogroups in a derivation cohort (n = 1,242). Model performance was first validated in 2 external cohorts to identify elevated left ventricular filling pressure (n = 84) and assess its prognostic value (n = 219) in patients with varying degrees of systolic and diastolic dysfunction. In 3 National Heart, Lung, and Blood Institute–funded HFpEF trials, the clinical significance of the model was further validated by assessing the relationships of the phenogroups with adverse clinical outcomes (TOPCAT [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function] trial, n = 518), cardiac biomarkers, and exercise parameters (NEAT-HFpEF [Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction] and RELAX-HF [Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure] pooled cohort, n = 346).ResultsThe DeepNN model showed higher area under the receiver-operating characteristic curve than 2016 American Society of Echocardiography guideline grades for predicting elevated left ventricular filling pressure (0.88 vs. 0.67; p = 0.01). The high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization and/or death, even after adjusting for global left ventricular and atrial longitudinal strain (hazard ratio [HR]: 3.96; 95% confidence interval [CI]: 1.24 to 12.67; p = 0.021). Similarly, in the TOPCAT cohort, the high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization or cardiac death (HR: 1.92; 95% CI: 1.16 to 3.22; p = 0.01) and higher event-free survival with spironolactone therapy (HR: 0.65; 95% CI: 0.46 to 0.90; p = 0.01). In the pooled RELAX-HF/NEAT-HFpEF cohort, the high-risk (vs. low-risk) phenogroup had a higher burden of chronic myocardial injury (p < 0.001), neurohormonal activation (p < 0.001), and lower exercise capacity (p = 0.001).ConclusionsThis publicly available DeepNN classifier can characterize the severity of diastolic dysfunction and identify a specific subgroup of patients with HFpEF who have elevated left ventricular filling pressures, biomarkers of myocardial injury and stress, and adverse events and those who are more likely to respond to spironolactone.     

Clinical characteristics,outcomes, and factors associated with mortality in Nocardia pneumonia: 18 years' real-world data from a tertiary care hospital in Karachi,Pakistan

BackgroundPulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.MethodsThis retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.ResultsSixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001).Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01–439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47–197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23–38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.ConclusionsThis study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.     

Ventricular Arrhythmias in Myocarditis: Characterization and Relationships With Myocardial Inflammation

BackgroundVentricular arrhythmias (VAs) have never been systematically investigated in patients with myocarditis at different stages.ObjectivesThe purpose of this study was to compare baseline and follow-up characteristics of VAs in patients with active myocarditis (AM) versus previous myocarditis (PM).MethodsA total of 185 consecutive patients (69% males, age 44 ± 15 years, left ventricular ejection fraction 49 ± 14%) with myocarditis and VA at index hospitalization, including ventricular fibrillation, ventricular tachycardia (VT), nonsustained ventricular tachycardia (NSVT), and Lown’s grade ≥2 premature ventricular complexes, were enrolled. AM and PM groups were defined based on endomyocardial biopsy and cardiac magnetic resonance findings. A subset of patients (n = 46, 25%) also underwent electroanatomic mapping and VA transcatheter ablation.ResultsAt presentation, AM patients (n = 123, 66%) more commonly had ventricular fibrillation (8 cases vs. 0 cases; p = 0.053), and both irregular (61% vs. 11%; p < 0.001) and polymorphic VA (NSVT and VT: 19% vs. 2%; p = 0.002; premature ventricular complexes: 63% vs. 16%; p < 0.001). Only in PM patients with NSVT or VT, the dominant morphology (right-bundle branch block with superior axis) was 100% predictive of abnormal LV inferoposterior substrate at both cardiac magnetic resonance and electroanatomic mapping. At 27 ± 7 months prospective follow-up, 55 patients (30%) experienced malignant VA (AM vs. PM, p = 0.385). Although a prevalence of polymorphic and irregular VA was confirmed in AM patients with persistent inflammation in follow-up (58%), a predominance of monomorphic and regular VA was found in AM patients after myocarditis healing (42%), as well as in PM patients (all p < 0.001).ConclusionsIn myocarditis patients, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis.     

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction

Background and aimsLow serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients.Methods and resultsMulticenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4–41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71–12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37–0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS −0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30–9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99–14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02–18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21–10.80, p = 0.022) were associated with AEs.ConclusionLow SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.     

Impact of Mediterranean diet on metabolic and inflammatory status of patients with polyvascular atherosclerotic disease

Background and aimsThe Mediterranean Diet (MD) represents a key player in cardiovascular disease prevention. Therefore, we aimed to assess the relationship between adherence to the MD and inflammatory, lipid and glycemic profile in patients affected by polyvascular atherosclerotic disease (PAD). We also investigated the incidence of long-term major adverse cardiovascular events (MACEs) according to MD adherence.Methods and resultsWe enrolled 107 patients with PAD, defined as the simultaneous involvement of at least two vascular districts. Adherence to the MD was estimated through a 9-item simplified form of the Mediterranean Diet Score. Improved fasting glycemic and LDL-cholesterol levels were reported in the high-adherence group compared with the low-adherence group (p < 0.001 and p = 0.0049, respectively). Both C-reactive protein and platelet-to-lymphocyte ratio were significantly lower in high-adherence patients than those with poor adherence to the MD (p = 0.0045 and p = 0.008, respectively). During follow-up (mean 34 ± 11 months), fatal events happened exclusively in the low-adherence group (58%), with an event-free survival of 37% compared with 87% in the moderate-adherence group and 70% in the high-adherence group (log-rank p-value < 0.001). Low adherence to the MD was associated with a higher incidence of MACEs in the Cox regression model adjusted for atherosclerotic risk factors (HR 12.23, 95% CI 4.00–37.39).ConclusionsHigh adherence to Mediterranean dietary pattern seems to be associated with improving inflammatory and metabolic status in patients suffering from PAD, potentially translating into better long-term cardiovascular outcomes. These findings provide evidence regarding the relevance of MD as a secondary preventive tool in this high-risk population.     

Titanium-Nitride-Oxide–Coated Versus Everolimus-Eluting Stents in Acute Coronary Syndrome: The Randomized TIDES-ACS Trial

ObjectivesThis study sought to compare next-generation cobalt-chromium–based titanium-nitride-oxide (TiNO)–coated stents with a platinum-chromium–based biodegradable polymer everolimus-eluting stent (EES) in patients with acute coronary syndrome (ACS).BackgroundPrevious generation TiNO-coated stents showed acceptable performance in patients with ACS.MethodsIn a multicenter, randomized trial, we randomly assigned 1,491 ACS patients (2:1) to receive either a TiNO-coated stent (n = 989) or EES (n = 502). The primary endpoint was the rate of a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization at 12-month follow-up. The co-primary endpoint was a composite of cardiac death, MI, or major bleeding at 18 months.ResultsA primary endpoint event occurred in 6.3% of patients in the TiNO-coated stent group versus in 7.0% in the EES group (hazard ratio: 0.93; 95% confidence interval: 0.71 to 1.22; p = 0.66 for superiority; p < 0.001 for noninferiority). A co-primary endpoint event occurred in 3.7% of the patients in the TiNO group and in 7.8% in the EES group (hazard ratio: 0.64; 95% confidence interval: 0.51 to 0.80; p = 0.001). TiNO-coated stents were associated with lower rates of cardiac death (0.6% vs. 2.6%; p = 0.002) and MI (2.2% vs. 5.0%; p = 0.007) at 18 months of follow-up. Rates of target lesion revascularization were not significantly different at 18 months (5.8% vs. 4.4%; p = 0.27).ConclusionsIn patients with ACS, cobalt-chromium–based TiNO-coated stents were noninferior to platinum-chromium–based biodegradable polymer EES for major cardiac events at 12 months, and were superior for the co-primary endpoint of cardiac death, MI, and bleeding at 18 months. (Comparison of Titanium-Nitride-Oxide-Coated Bio-Active-Stent (Optimax™) to the Drug (Everolimus) -Eluting Stent (Synergy™) in Acute Coronary Syndrome [TIDES-ACS]; NCT02049229)     

Chimney Stenting for Coronary Occlusion During TAVR: Insights From the Chimney Registry

ObjectivesThe aim of this study was to determine the safety and efficacy of chimney stenting, a bailout technique to treat coronary artery occlusion (CAO).BackgroundCAO during transcatheter aortic valve replacement (TAVR) is a rare but often fatal complication.MethodsIn the international Chimney Registry, patient and procedural characteristics and data on outcomes are retrospectively collected from patients who underwent chimney stenting during TAVR.ResultsTo date, 16 centers have contributed 60 cases among 12,800 TAVR procedures (0.5%). Chimney stenting was performed for 2 reasons: 1) due to the development of an established CAO (n = 25 [41.6%]); or 2) due to an impending CAO (n = 35 [58.3%]). The majority of cases (92.9%) had 1 or more classical risk factors for CAO. Upfront coronary protection was performed in 44 patients (73.3%). Procedural and in-hospital mortality occurred in 1 and 2 patients, respectively. Myocardial infarction (52.0% vs. 0.0%; p < 0.01), cardiogenic shock (52.0% vs. 2.9%; p < 0.01), and resuscitation (44.0% vs. 2.9%; p < 0.01) all occurred more frequently in patients with established CAO compared with those with impending CAO. The absence of upfront coronary protection was the sole independent risk factor for the combined endpoint of death, cardiogenic shock, or myocardial infarction. During a median follow-up time of 612 days (interquartile range: 405 to 842 days), 2 cases of stent failure were reported (1 in-stent restenosis, 1 possible late stent thrombosis) after 157 and 374 days.ConclusionsChimney stenting appears to be an acceptable bailout technique for CAO, with higher event rates among those with established CAO and among those without upfront coronary protection.     

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.     

Patient Characteristics and Clinical Outcomes of Type 1 Versus Type 2 Myocardial Infarction

BackgroundType 2 myocardial infarction (MI) patients may have different characteristics and outcomes when compared with type 1 MI.ObjectivesThe purpose of this study was to compare patients with type 1 MI to those with type 2 MI in the United States.MethodsUsing the Nationwide Readmissions Database, MI patients were categorized over the 3 months following the introduction of an International Classification of Diseases-10th Revision code specific for type 2 MI. Baseline characteristics and inpatient and post-discharge outcomes among both cohorts were compared.ResultsThere were 216,657 patients with type 1 MI, 37,765 patients with type 2 MI, and 1,525 patients with both type 1 and 2 MI. Patients with type 2 MI were older (71 years vs. 69 years; p < 0.001), were more likely to be women (47.3% vs. 40%; p < 0.001), and had higher prevalence of heart failure (27.9% vs. 10.9%; p < 0.001), kidney disease (35.7% vs. 25.7%; p < 0.001), and atrial fibrillation (31% vs. 21%; p < 0.001). Rates of coronary angiography (10.9% vs. 57.3%; p < 0.001), percutaneous coronary intervention (1.7% vs. 38.5%; p < 0.001), and coronary artery bypass grafting (0.4% vs. 7.8%; p < 0.001) were lower among type 2 MI patients. Patients with type 2 MI had lower risk of in-hospital mortality (adjusted odds ratio: 0.57 [95% confidence interval: 0.54 to 0.60]) and 30-day MI readmission (adjusted odds ratio: 0.46 [95% confidence interval: 0.35 to 0.59]). There was no difference in risk of 30-day all-cause or heart failure readmission.ConclusionsPatients with type 2 MI have a unique cardiovascular phenotype when compared with type 1 MI, and are managed in a heterogenous manner. Validated management strategies for type 2 MI are needed.     

Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study

ObjectivesThis study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling.BackgroundAlthough regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear.MethodsA total of 65 patients and 35 healthy control subjects underwent adenosine (140 μg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm.ResultsPatients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: −0.12 ml/g/min; 95% confidence interval: −0.23 to −0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: −0.15 ml/g/min; 95% confidence interval: −0.28 to −0.03 ml/g/min; p = 0.013).ConclusionsPatients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.     

Myocardial Histopathology in Patients With Obstructive Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is characterized by multiple pathological features including myocyte hypertrophy, myocyte disarray, and interstitial fibrosis.ObjectivesThis study sought to correlate myocardial histopathology with clinical characteristics of patients with obstructive HCM and post-operative outcomes following septal myectomy.MethodsThe authors reviewed the pathological findings of the myocardial specimens from 1,836 patients with obstructive HCM who underwent septal myectomy from 2000 to 2016. Myocyte hypertrophy, myocyte disarray, interstitial fibrosis, and endocardial thickening were graded and analyzed.ResultsThe median age at operation was 54.2 years (43.5 to 64.3 years), and 1,067 (58.1%) were men. A weak negative correlation between myocyte disarray and age at surgery was identified (ρ = ?0.22; p < 0.001). Myocyte hypertrophy (p < 0.001), myocyte disarray (p < 0.001), and interstitial fibrosis (p < 0.001) were positively associated with implantable cardioverter-defibrillator implantation. Interstitial fibrosis (p < 0.001) and endocardial thickening (p < 0.001) were associated with atrial fibrillation pre-operatively. In the Cox survival model, older age (p < 0.001), lower degree of myocyte hypertrophy (severe vs. mild hazard ratio: 0.41; 95% confidence interval: 0.19 to 0.86; p = 0.040), and lower degree of endocardial thickening (moderate vs. mild hazard ratio: 0.75; 95% confidence interval: 0.58 to 0.97; p = 0.019) were independently associated with worse post-myectomy survival. Among 256 patients who had genotype analysis, patients with pathogenic or likely pathogenic variants (n = 62) had a greater degree of myocyte disarray (42% vs. 15% vs. 20%; p = 0.022). Notably, 13 patients with pathogenic or likely pathogenic genetic variants of HCM had no myocyte disarray.ConclusionsHistopathology was associated with clinical manifestations including the age of disease onset and arrhythmias. Myocyte hypertrophy and endocardial thickening were negatively associated with post-myectomy mortality.     

Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease

BackgroundPatients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.ObjectivesThe aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial.MethodsCox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection.ResultsEUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex.ConclusionsAlthough women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822)     

Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Randomized Disrupt PAD III Trial

ObjectivesThe study sought to compare short-term outcomes in patients with femoropopliteal artery calcification receiving vessel preparation with intravascular lithotripsy (IVL) or percutaneous transluminal angioplasty (PTA) prior to drug-coated balloon (DCB) for symptomatic peripheral artery disease.BackgroundEndovascular treatment of calcified peripheral artery lesions is associated with suboptimal vessel expansion and increased complication risk. Although initial results from single-arm studies with IVL have been reported, comparative evidence from randomized trials is lacking for most devices in the presence of heavy calcification.MethodsThe Disrupt PAD III (Shockwave Medical Peripheral Lithoplasty System Study for PAD) randomized trial enrolled patients with moderate or severe calcification in a femoropopliteal artery who underwent vessel preparation with IVL or PTA prior to DCB or stenting. The primary endpoint was core lab–adjudicated procedural success (residual stenosis ≤30% without flow-limiting dissection) prior to DCB or stenting.ResultsIn patients receiving IVL (n = 153) or PTA (n = 153), procedural success was greater in the IVL group (65.8% vs. 50.4%; p = 0.01) and the percentage of lesions with residual stenosis ≤30% (66.4% vs. 51.9%; p = 0.02) was greater in the IVL group, while flow-limiting dissections occurred more frequently in the PTA group (1.4% vs. 6.8%; p = 0.03). Post-dilatation (5.2% vs. 17.0%; p = 0.001) and stent placement (4.6% vs. 18.3%; p < 0.001) were also greater in the PTA group. The rates of major adverse events (IVL: 0% vs. PTA: 1.3%; p = 0.16) and clinically driven target lesion revascularization (IVL: 0.7% vs. PTA: 0.7%; p = 1.0) at 30 days were comparable between groups.ConclusionsIVL is an effective vessel preparation strategy that facilitates definitive endovascular treatment in calcified femoropopliteal arteries in patients with peripheral artery disease. (Shockwave Medical Peripheral Lithoplasty System Study for PAD [Disrupt PAD III]; NCT02923193)     

Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation

ObjectivesThe goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.BackgroundFMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.MethodsVasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.ResultsA total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p < 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p < 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p < 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p < 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.ConclusionsIschemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.     

Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography

ObjectivesThe purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE).BackgroundB-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE.MethodsThe authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up.ResultsAccording to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction.ConclusionsSevere stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020–The International Stress Echo Study [SE2020]; NCT03049995)     

Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy

BackgroundRisk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal.ObjectivesThe goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM.MethodsThis was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death.ResultsIn 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p < 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%, >35%) was significantly superior to LVEF with the 35% cutoff (Harrell’s C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p < 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF >35% had significantly higher risk (annual event rate 3%; p = 0.007).ConclusionsIn a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation.