Prasad, Abhiram

Introduction Apical ballooning syndrome (ABS) is typically associated with an antecedent stressful situation. Affected patients have been reported to have higher frequencies of premorbid affective disorders. We hypothesised that patients with ABS would have elevated levels of neuroticism (tendency to experience negative affect) and greater vulnerability to stress. Methods In this cross-sectional study, all active participants in the Mayo Clinic ABS prospective follow-up registry were invited to complete the third edition of the NEO Personality Inventory (NEO-PI-3). The NEO-PI-3 is the universally accepted measure of the ‘Five-Factor Model’ of personality. Inventory responses were scored using the NEO-PI-3 computer program and the data were compared with US normative sample used in standardisation of the inventory. Significance was set at 0.0014 to account for multiple comparisons. Results Of 106 registry participants approached, 53 completed the inventory. There was no difference in age, gender, time from ABS diagnosis, type of antecedent stressor (emotional, physical or none) or severity of initial illness between the responders and non-responders. Responders had mean Neuroticism T-scores of 48.0±10.6 (95% CI 45.1 to 50.9); p=0.18, when compared with the normal mean of 50. There was also no significant difference in the facet scale of Vulnerability: 46.9±8.4 (44.6 to 49.2), p=0.038, at α=0.0014. Conclusions Contrary to our hypothesis, patients with ABS do not manifest higher levels of neuroticism and do not have greater vulnerability to stress than the general population. These findings have implications for the clinicians’ perception of, and approach to, patients with ABS.

Background— Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention. Methods and Results— We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected c -statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected c -statistic of 0.77. Conclusions— We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention.

Objective There is a paucity of data on the impact of complete revascularisation (CR) following percutaneous coronary intervention (PCI) among patients with diabetes with multivessel coronary disease. In this study, we assess the impact of CR, using a relatively simple anatomical definition, on long-term outcomes (median follow-up 7.9 years) in patients with diabetes, and compare with patients without diabetes. Methods 5350 patients with multivessel disease (coronary stenoses ≥70% in ≥2 major epicardial arteries) who underwent PCI between January 1997 and June 2011 were included. Patients were divided into 4 groups according to diabetes and CR status (absence of residual coronary stenosis in major, predominantly proximal, epicardial segments according to Coronary Artery Surgery Study (CASS) classification). Results Patients with diabetes and patients with incomplete revascularisation (IR) had more adverse clinical and angiographic characteristics. IR was frequent in patients with diabetes, and was marginally more common than in patients without diabetes (47% vs 44%, p<0.001). Patients with diabetes and patients without diabetes had higher mortality rates after IR than after CR (HR 1.56 (95% CI (1.39 to 1.85), p<0.001 for patients with diabetes and 1.70 (95% CI (1.50 to 1.92), p<0.001) in patients without diabetes). However, the absolute risk was higher for patients with diabetes (5-year mortality: IR 35.8%, CR 21.2%) than in patients without diabetes (5-year mortality: IR 22.2%, CR 14.1%). In a multivariable model, IR and diabetes mellitus were independent predictors of total mortality. This effect was present in the bare metal stent and drug-eluting stent eras and in patients with stable disease and acute coronary syndromes. Conclusions CR is associated with lower long-term mortality in patients with diabetes and patients without diabetes. However the difference was significantly greater in patients with diabetes compared with patients without diabetes.

Background Survivors of ventricular fibrillation out of hospital cardiac arrest ( VF ‐ OHCA ) due to a potentially reversible cause such as acute myocardial infarction (MI) or ischemia are considered to be at low risk of recurrent arrhythmia. Implantable cardioverter defibrillators ( ICD ) are not routinely recommended in such patients. However, the outcome of these patients in the era of rapid coronary revascularization and ICD therapy is not known. Methods and Results We examined the outcome of 114 consecutive survivors of VF OHCA due to acute MI or ischemia in Olmsted County, MN from 1990 to 2011. An ICD was implanted in 45/114 patients. ICD recipients had lower EF [median ( IQR ) 38 (26 to 54) versus 48 (35 to 58) %, P =0.04]. During a median ( IQR ) follow‐up of 9.9 (4.4 to 14.6) years, ICD implantation was associated with reduced cardiac mortality ( HR 0.24 [0.07 to 0.88], P =0.031) and a trend towards reduced all‐cause mortality ( HR 0.56 [0.30 to 1.02], P =0.059) after adjusting for the first principal component. One or more appropriate ICD therapies were delivered in 19/45, with half of the patients receiving therapy within 1 year. Patients with EF ≤35% at discharge continued to be at long‐term risk for ICD therapy compared with those with EF >35% who were at increased risk predominantly in the first 8 months. EF and revascularization were not significantly associated with ICD therapy in the multivariable analysis. Conclusions Patients with VF ‐ OHCA in the setting of acute MI or myocardial ischemia remain at high risk of recurrent ventricular arrhythmias, particularly if EF ≤35%. This suggests that ICD implantation may be reasonable if EF ≤35%.

Objectives: To retrospectively evaluate outcomes among cancer survivors previously treated with thoracic radiotherapy (RT) who later underwent percutaneous coronary intervention (PCI). Methods: From 1998 to 2012, 76 patients first received curative RT (>30 Gy, except for Hodgkin lymphoma patients) involving the heart and lungs followed by PCI. Heart and lung–specific dosimetric parameters were correlated with overall survival (OS) and cardiac-specific survival by Cox variate methods. Results: The mean interval between cancer diagnosis and PCI was 3.7 years (range, 0.1 to 12.6 y). Median follow-up since cancer diagnosis was 5.5 years. At analysis, 46 patients (61%) were alive, 5 (7%) died of cardiac causes, and 9 (12%) of cancer. Higher maximum RT heart dose was related to poorer OS since PCI (P=0.009). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (P=0.005) and higher mean heart dose (P<0.001) were related to poorer OS since cancer diagnosis. β-Blockers, higher mean heart dose (hazard ratio [HR]=1.49, P<0.001), and percentage of targeted volume or organ receiving ≥40 Gy for heart doses (HR=1.32, P<0.001) were associated with poorer non–cancer-specific survival since cancer diagnosis. Diabetes (HR=3.84, P=0.008) and increased percentage of targeted volume or organ receiving ≥45 Gy (HR=1.01 per additional 100 cm3 irradiated, P=0.01) for the heart decreased major adverse cardiac event–free survival. Conclusions: Prior heart and lung–directed RT had volume-dependent and dose-dependent adverse effects on long-term cardiac outcomes for patients subsequently treated with PCI. RT planning that minimizes heart and lung irradiation doses should be encouraged.

Objective— Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. Approach and Results— Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (−17.7±14.7% versus −6.3±13.9%; P <0.01) and microchannels (−15.9±15.9% versus −6.4±13.5%; P <0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change ( P <0.01 and P =0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; −22.1±14.6% versus −10.9±15.6% and −10.9±15.6%; P =0.07 and P =0.06, respectively). Conclusions— Epicardial endothelial dysfunction was associated with optical coherence tomography –identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

Abstract Aims Exome sequencing was used to genotype comprehensively a Takotsubo (stress) cardiomyopathy (TC) cohort, enabling investigation of a vast 486 gene network for adrenergic signalling. Methods and results Twenty-eight TC subjects, including a mother–daughter pair and five recurrent cases, underwent whole-exome sequencing. Frequencies of 17 common, functional adrenergic polymorphisms were statistically similar to those of population controls. Filtering for rare, predicted-deleterious, catecholamine/adrenergic signalling variants revealed heterozygosity in 55 genes in TC cases and 59 genes in healthy controls. Overall allele burden was similar and did not discriminate clinical variables among TC subjects, but gene identities were largely cohort specific, and TC cases were enriched for variants within functional domains (68% vs. 48%, P = 0.031). Two-thirds of TC cases carried more than one filtered adrenergic pathway variant, and 11 genes harboured a variant in ≥2 cases. The mother–daughter pair shared missense variants in highly conserved functional domains of ADH5, CACNG1, EPHA4, and PRKCA. An adrenergic pathway-independent analysis of the cohort exposed no common gene for TC. Conclusions Overall, these data support genetic heterogeneity in TC susceptibility and a likely polygenic basis, conferring a cumulative effect on adrenergic pathway dysregulation in a subset of individual subjects. Study of larger cohorts and non-coding regulatory regions is warranted to define genetic risk factors for TC further.

Background— There is controversy about the diagnostic and prognostic significance of percutaneous coronary intervention–related myocardial infarction, especially with the use of cardiac troponin T (cTnT). This analysis was designed to address the question of the presence and the level of a prognostic cTnT threshold. Methods and Results— We evaluated 5268 consecutive patients who underwent nonemergent percutaneous coronary intervention between 2000 and 2009 with a preprocedural cTnT level below the upper limit of normal (ULN, ≤0.01 ng/mL). Postprocedural cTnT and creatine kinase-MB mass levels (ULN, 6.7 ng/mL in men and 3.8 ng/mL in women) were found to be associated with 3-month mortality in Cox proportional hazard models (hazard ratio per doubling of cTnT, 1.24; 95% confidence interval, 1.08–1.43; P =0.003 and hazard ratio per doubling of creatine kinase-MB, 1.30; 95% confidence interval, 1.05–1.60; P =0.018), adjusted for the Mayo Clinic risk scores for in-hospital and postdischarge mortality. The optimal prognostic threshold for 3-month mortality was 25× ULN for cTnT (hazard ratio, 4.53; 99% confidence interval, 1.59–12.9; P <0.001), which provided similar information as a value of 5× ULN for creatine kinase-MB (hazard ratio, 4.31; 99% confidence interval, 1.27–14.6; P =0.002). The cumulative mortality rate was 0.6% at 91 days. Conclusions— A significant association of postpercutaneous coronary intervention cardiac biomarker elevation with a small number of postpercutaneous coronary intervention outcomes was noted for the early (first 91 days) follow-up period with an identifiable optimal threshold of 25× ULN (0.25, ng/mL) for cTnT, which provided similar early outcome information as a cutoff of 5× ULN for creatine kinase-MB.