Parag Goyal

Mitral Apparatus Assessment by Delayed Enhancement CMR: Relative Impact of Infarct Distribution on Mitral Regurgitation

OBJECTIVES This study sought to assess patterns and functional consequences of mitral apparatus infarction after acute myocardial infarction (AMI). BACKGROUND The mitral apparatus contains 2 myocardial components: papillary muscles and the adjacent left ventricular (LV) wall. Delayed-enhancement cardiac magnetic resonance (DE-CMR) enables in vivo study of inter-relationships and potential contributions of LV wall and papillary muscle infarction (PMI) to mitral regurgitation (MR). METHODS Multimodality imaging was performed: CMR was used to assess mitral geometry and infarct pattern, including 3D DE-CMR for PMI. Echocardiography was used to measure MR. Imaging occurred 27 ± 8 days after AMI (CMR, echocardiography within 1 day). RESULTS A total of 153 patients with first AMI were studied; PMI was present in 30% (n = 46 [72% posteromedial, 39% anterolateral]). When stratified by angiographic culprit vessel, PMI occurred in 65% of patients with left circumflex, 48% with right coronary, and only 14% of patients with left anterior descending infarctions (p <0.001). Patients with PMI had more advanced remodeling as measured by LV size and mitral annular diameter (p <0.05). Increased extent of PMI was accompanied by a stepwise increase in mean infarct transmurality within regional LV segments underlying each papillary muscle (p <0.001). Prevalence of lateral wall infarction was 3-fold higher among patients with PMI compared to patients without PMI (65% vs. 22%, p <0.001). Infarct distribution also impacted MR, with greater MR among patients with lateral wall infarction (p = 0.002). Conversely, MR severity did not differ on the basis of presence (p = 0.19) or extent (p = 0.12) of PMI, or by angiographic culprit vessel. In multivariable analysis, lateral wall infarct size (odds ratio 1.20/% LV myocardium [95% confidence interval: 1.05 to 1.39], p = 0.01) was independently associated with substantial (moderate or greater) MR even after controlling for mitral annular (odds ratio 1.22/mm [1.04 to 1.43], p = 0.01), and LV end-diastolic diameter (odds ratio 1.11/mm [0.99 to 1.23], p = 0.056). CONCLUSIONS Papillary muscle infarction is common after AMI, affecting nearly one-third of patients. Extent of PMI parallels adjacent LV wall injury, with lateral infarction-rather than PMI-associated with increased severity of post-AMI MR.

Characteristics of Hospitalizations for Heart Failure with Preserved Ejection Fraction

BACKGROUND Hospitalizations for heart failure with preserved ejection fraction (HFpEF) are increasing. There are limited data examining national trends in patients hospitalized with HFpEF. METHODS Using the Nationwide Inpatient Sample, we examined 5,046,879 hospitalizations with a diagnosis of acute heart failure in 2003-2012, stratifying hospitalizations by HFpEF and heart failure with reduced ejection fraction (HFrEF). Patient and hospital characteristics, in-hospital mortality, and length of stay were examined. RESULTS Compared with HFrEF, those with HFpEF were older, more commonly female, and more likely to have hypertension, atrial fibrillation, chronic lung disease, chronic renal failure, and anemia. Over time, HFpEF comprised increasing proportions of men and patients aged ≥75 years. In-hospital mortality rate for HFpEF decreased by 13%, largely due to improved survival in those aged ≥65 years. Multivariable regression analyses showed that pulmonary circulation disorders, liver disease, and chronic renal failure were independent predictors of in-hospital mortality, whereas treatable diseases including hypertension, coronary artery disease, and diabetes were inversely associated. CONCLUSIONS This study represents the largest cohort of patients hospitalized with HFpEF to date, yielding the following observations: number of hospitalizations for HFpEF was comparable with that of HFrEF; patients with HFpEF were most often women and elderly, with a high burden of comorbidities; outcomes appeared improved among a subset of patients; pulmonary hypertension, liver disease, and chronic renal failure were strongly associated with poor outcomes.

Variability Among Research Diagnostic Interview Instruments in the Application of DSM-IV-TR Criteria for Pediatric Bipolar Disorder

OBJECTIVE The DSM-IV-TR criteria for a manic episode and bipolar disorder (BD) were developed for adults but are used for children. The manner in which clinicians and researchers interpret these criteria may have contributed to the increase in BD diagnoses given to youth. Research interviews are designed to improve diagnostic reliability and validity, but vary in how they incorporate DSM-IV-TR criteria for pediatric BD. METHOD We examined DSM-IV-TR criteria and the descriptive text for a manic episode and the mania sections of six commonly used pediatric diagnostic research interviews focusing on the following: interpretation of DSM-IV-TR, recommendations for administration, and scoring methods. RESULTS There are differences between the DSM-IV-TR manic episode criteria and descriptive text. Instruments vary in several ways including in their conceptualization of the mood criterion, whether symptoms must represent a change from the childs usual state, and whether B-criteria are required to co-occur with the A-criterion. Instruments also differ on recommendations for administration and scoring methods. CONCLUSIONS Given the differences between DSM-IV-TR manic episode criteria and explanatory text, it is not surprising that there is considerable variation between diagnostic instruments based on DSM-IV-TR. These differences likely lead to dissimilarities in subjects included in BD research studies and inconsistent findings across studies. The field of child psychiatry would benefit from more uniform methods of assessing symptoms and determining pediatric BD diagnoses. We discuss recommendations for changes to future instruments, interviews, assessment, and the DSM-5.

Improved left ventricular mass quantification with partial voxel interpolation: in vivo and necropsy validation of a novel cardiac MRI segmentation algorithm.

Background— Cardiac magnetic resonance (CMR) typically quantifies LV mass (LVM) by means of manual planimetry (MP), but this approach is time-consuming and does not account for partial voxel components— myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM. Methods and Results— LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared with LVM quantified on echocardiography (echo) and an ex vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time versus MP (0:21±0:04 versus 4:18±1:02 minutes; P <0.001). ASFV mass (136±35 g) was slightly lower than MP (139±35; Δ=3±9 g, P <0.001). Both methods yielded similar proportions of patients with LV remodeling ( P =0.73) and hypertrophy ( P =1.00). Regarding partial voxel segmentation, ASPV yielded higher LVM (159±38 g) than MP (Δ=20±10 g) and ASFV (Δ=23±6 g, both P <0.001), corresponding to relative increases of 14% and 17%. In multivariable analysis, magnitude of difference between ASPV and ASFV correlated with larger voxel size (partial r =0.37, P <0.001) even after controlling for LV chamber volume ( r =0.28, P =0.002) and total LVM ( r =0.19, P =0.03). Among patients, ASPV yielded better agreement with echo (Δ=20±25 g) than did ASFV (Δ=43±24 g) or MP (Δ=40±22 g, both P <0.001). Among laboratory animals, ASPV and ex vivo results were similar (Δ=1±3 g, P =0.3), whereas ASFV (6±3 g, P <0.001) and MP (4±5 g, P =0.02) yielded small but significant differences with LVM at necropsy. Conclusions— Automated segmentation of myocardial partial voxels yields a 14–17% increase in LVM versus full voxel segmentation, with increased differences correlated with lower spatial resolution. Partial voxel segmentation yields improved CMR agreement with echo and necropsy-verified LVM.Background— Cardiac magnetic resonance (CMR) typically quantifies LV mass (LVM) by means of manual planimetry (MP), but this approach is time-consuming and does not account for partial voxel components— myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM. Methods and Results— LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared with LVM quantified on echocardiography (echo) and an ex vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time versus MP (0:21±0:04 versus 4:18±1:02 minutes; P<0.001). ASFV mass (136±35 g) was slightly lower than MP (139±35; &Dgr;=3±9 g, P<0.001). Both methods yielded similar proportions of patients with LV remodeling (P=0.73) and hypertrophy (P=1.00). Regarding partial voxel segmentation, ASPV yielded higher LVM (159±38 g) than MP (&Dgr;=20±10 g) and ASFV (&Dgr;=23±6 g, both P<0.001), corresponding to relative increases of 14% and 17%. In multivariable analysis, magnitude of difference between ASPV and ASFV correlated with larger voxel size (partial r=0.37, P<0.001) even after controlling for LV chamber volume (r=0.28, P=0.002) and total LVM (r=0.19, P=0.03). Among patients, ASPV yielded better agreement with echo (&Dgr;=20±25 g) than did ASFV (&Dgr;=43±24 g) or MP (&Dgr;=40±22 g, both P<0.001). Among laboratory animals, ASPV and ex vivo results were similar (&Dgr;=1±3 g, P=0.3), whereas ASFV (6±3 g, P<0.001) and MP (4±5 g, P=0.02) yielded small but significant differences with LVM at necropsy. Conclusions— Automated segmentation of myocardial partial voxels yields a 14–17% increase in LVM versus full voxel segmentation, with increased differences correlated with lower spatial resolution. Partial voxel segmentation yields improved CMR agreement with echo and necropsy-verified LVM.

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

Background Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. Methods and Results The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). Conclusion Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

Comparison of Trends in Incidence, Revascularization, and In-Hospital Mortality in ST-Elevation Myocardial Infarction in Patients With Versus Without Severe Mental Illness.

Patients with severe mental illness (SMI), including schizophrenia and bipolar disorder, are at elevated risk of ST-elevation myocardial infarction (STEMI) but have previously been reported as less likely to receive revascularization. To study the persistence of these findings over time, we examined trends in STEMI incidence, revascularization, and in-hospital mortality for patients with and without SMI in the National Inpatient Sample from 2003 to 2012. We further used multivariate logistic regression analysis to assess the odds of revascularization and in-hospital mortality. SMI was present in 29,503 of 3,058,697 (1%) of the STEMI population. Patients with SMI were younger (median age 58 vs 67 years), more likely to be women (44% vs 38%), and more likely to have several co-morbidities, including diabetes, chronic pulmonary disease, substance abuse, and obesity (p <0.001 for all). Over time, STEMI incidence significantly decreased in non-SMI (p for trend <0.001) but not in SMI (p for trend 0.14). Revascularization increased in all subgroups (p for trend <0.001) but remained less common in SMI. In-hospital mortality decreased in non-SMI (p for trend = 0.004) but not in SMI (p for trend 0.10). After adjustment, patients with SMI were less likely to undergo revascularization (odds ratio 0.59, 95% CI 0.52 to 0.61, p <0.001), but SMI was not associated with increased in-hospital mortality (odds ratio 0.97, 95% CI 0.93 to 1.01, p = 0.16). In conclusion, in contrast to the overall population, the incidence of STEMI is not decreasing in patients with SMI. Despite changes in the care of STEMI, patients with SMI remain less likely to receive revascularization therapies.

Incidence, prognosis, and factors associated with cardiac arrest in patients hospitalized with acute coronary syndromes (the Global Registry of Acute Coronary Events Registry)

ObjectivesContemporary data are lacking with respect to the incidence rates of, factors associated with, and impact of cardiac arrest from ventricular fibrillation or tachycardia (VF-CA) on hospital survival in patients admitted with an acute coronary syndrome (ACS). The objectives of this multinational study were to characterize trends in the magnitude of in-hospital VF-CA complicating an ACS and to describe its impact over time on hospital prognosis. MethodsIn 59 161 patients enrolled in the Global Registry of Acute Coronary Events Study between 2000 and 2007, we determined the incidence, prognosis, and factors associated with VF-CA. ResultsOverall, 3618 patients (6.2%) developed VF-CA during their hospitalization for an ACS. Incidence rates of VF-CA declined over time. Patients who experienced VF-CA were on average older and had a greater burden of cardiovascular disease, yet were less likely to receive evidence-based cardiac therapies than patients in whom VF-CA did not occur. Hospital death rates were 55.3% and 1.5% in patients with and without VF-CA, respectively. There was a greater than 50% decline in the hospital death rates associated with VF-CA during the years under study. Patients with a VF-CA occurring after 48 h were at especially high risk for dying during hospitalization (82.8%). ConclusionDespite reductions in the magnitude of, and short-term mortality from, VF-CA, VF-CA continues to exert an adverse effect on survival among patients hospitalized with an ACS. Opportunities exist to improve the identification and treatment of ACS patients at risk for VF-CA to reduce the incidence of, and mortality from, this serious arrhythmic disturbance.

Sex‐ and Race‐Related Differences in Characteristics and Outcomes of Hospitalizations for Heart Failure With Preserved Ejection Fraction

Background Sex and race have emerged as important contributors to the phenotypic heterogeneity of heart failure with preserved ejection fraction (HFpEF). However, there remains a need to identify important sex‐ and race‐related differences in characteristics and outcomes using a nationally representative cohort. Methods and Results Data were obtained from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project—Nationwide Inpatient Sample files between 2008 and 2012. Hospitalizations with a diagnosis of HFpEF were included for analysis. Demographics, hospital characteristics, and age‐adjusted comorbidity prevalence rates were compared between men and women and whites and blacks. In‐hospital mortality was determined and compared for each subgroup. Multivariable regression analyses were used to identify and compare correlates of in‐hospital mortality for each subgroup. A sample of 1 889 608 hospitalizations was analyzed. Men with HFpEF were slightly younger than women with HFpEF and had a higher Elixhauser comorbidity score. Men experienced higher in‐hospital mortality compared with women, a finding that was attenuated after adjusting for comorbidity. Blacks with HFpEF were younger than whites with HFpEF, with lower rates of most comorbidities. Hypertension, diabetes, anemia, and chronic renal failure were more common among blacks. Blacks experienced lower in‐hospital mortality compared with whites, even after adjusting for age and comorbidity. Important correlates of mortality among all 4 subgroups included pulmonary circulation disorders, liver disease, and chronic renal failure. Atrial fibrillation was an important correlate of mortality only among women and blacks. Conclusions Differences in patient characteristics and outcomes reinforce the notion that sex and race contribute to the phenotypic heterogeneity of HFpEF.

Myocardial perfusion pattern for stratification of ischemic mitral regurgitation response to percutaneous coronary intervention

ObjectiveIschemic mitral regurgitation (MR) is common, but its response to percutaneous coronary intervention (PCI) is poorly understood. This study tested the utility of myocardial perfusion imaging (MPI) for the stratification of MR response to PCI. MethodsMPI and transthoracic echocardiography (echo) were performed among patients undergoing PCI. MPI was used to assess stress/rest myocardial perfusion. MR was assessed via echo (performed before and after PCI). ResultsA total of 317 patients with abnormal myocardial perfusion on MPI underwent echo 25±39 days before PCI. MR was present in 52%, among whom 24% had advanced (≥moderate) MR. MR was found to be associated with left ventricular (LV) chamber dilation on MPI and echo (both P<0.001). The magnitude of global LV perfusion deficits increased in relation to MR severity (P<0.01). Perfusion differences were greatest for global summed rest scores, which were 1.6-fold higher among patients with advanced MR versus those with mild MR (P=0.004), and 2.4-fold higher versus those without MR (P<0.001). In multivariate analysis, advanced MR was found to be associated with a fixed perfusion defect size on MPI [odds ratio 1.16 per segment (confidence interval 1.002–1.34), P=0.046], independent of LV volume [odds ratio 1.10 per 10 ml (confidence interval 1.04–1.17), P=0.002]. Follow-up via echo (1.0±0.6 years) demonstrated MR to decrease (≥1 grade) in 31% of patients and increase in 12% of patients. Patients with increased MR after PCI had more severe inferior perfusion defects on baseline MPI (P=0.028), whereas defects in other distributions and LV volumes were similar (P=NS). ConclusionThe extent and distribution of single-photon emission computed tomography-evidenced myocardial perfusion defects impact MR response to revascularization. An increased magnitude of inferior fixed perfusion defects predicts post-PCI progression of MR.

Impact of Exercise Programs on Hospital Readmission Following Hospitalization for Heart Failure: A Systematic Review

Given persistently high 30-day readmission rates among patients hospitalized for heart failure, there is an ongoing need to identify new interventions to reduce readmissions. Although exercise programs can improve outcomes among ambulatory heart failure patients, it is not clear whether this benefit extends to reducing readmissions following heart failure hospitalization. We therefore conducted a systematic review of the literature to identify randomized controlled trials examining the impact of exercise programs on hospital readmissions among patients recently hospitalized for heart failure. We searched Ovid MEDLINE, EMBASE, and the Wiley Cochrane Library for studies that fulfilled pre-defined criteria, including that the exercise program pre-specify activity type and exercise frequency, duration, and intensity. Exercise interventions could occur at any location including within the hospital, at an outpatient facility, or at home. Among 1213 unique publications identified, only one study fulfilled inclusion criteria. This study was a single-site randomized controlled trial that consisted of a 12-week exercise program in a cohort of 105 patients with a principal diagnosis of heart failure at a metropolitan hospital in Australia. This study revealed a reduction in 12-month all-cause and cardiovascular-related hospitalization rates. However, inferences were limited by its single-site study design, small sample size, premature termination, and high risk for selection, performance, and detection bias. As no studies have built upon the findings of this study, it remains unknown whether exercise programs can improve readmission rates among patients recently hospitalized for heart failure, a significant gap in the literature.