Faris Araj

Hypoglycemia From a Cardiologist's Perspective

Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia triggers activation of the sympathoadrenal system, leading to an increase in counter‐regulatory hormones and, consequently, increased myocardial workload and oxygen demand. Additionally, hypoglycemia triggers proinflammatory and hematologic changes that provide the substrate for possible myocardial ischemia in the already‐diseased diabetic cardiovascular system. Hypoglycemia creates electrophysiologic alterations causing P‐R–interval shortening, ST‐segment depression, T‐wave flattening, reduction of T‐wave area, and QTc‐interval prolongation. Patients who experience hypoglycemia are at an increased risk of silent ischemia as well as QTc prolongation and consequent arrhythmias. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an increase in all‐cause mortality with intensive glycemic control, whereas the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study and Veterans Affairs Diabetes Trial (VADT) showed no benefit with aggressive glycemic control. Women, elderly patients, and those with renal insufficiency are more vulnerable to hypoglycemic events. In fact, hypoglycemia is the most common metabolic complication experienced by older patients with DM in the United States. The concurrent use of medications like β‐blockers warrants caution in DM because they can mask warning signs of hypoglycemia. Here we aim to elucidate the pathophysiology, review the electrocardiographic changes, analyze the current clinical literature, and consider the safety considerations of hypoglycemia as it relates to the cardiovascular system. In conclusion, in the current era of DM and its vascular ramifications, hypoglycemia from a cardiologists perspective deserves due attention.

Concentric left ventricular hypertrophy as assessed by cardiac magnetic resonance imaging and risk of death in cardiac transplant recipients

BACKGROUND Although risk factors for left ventricular (LV) hypertrophy in the native heart are well known, as is its association with increased risk of adverse outcomes, such information is poorly defined in heart transplant (HTx) recipients. We determined whether increased LV mass and concentricity (mass/volume) were associated with death in patients after HTx. METHODS Between May 2003 and May 2006, 140 HTx recipients underwent cardiac magnetic resonance imaging (MRI). Clinical characteristics associated with increased LV mass were determined. Cox proportional hazard models were constructed to assess the relationship of LV mass and concentricity with death. RESULTS MRIs were acquired a median of 6.0 years after transplant. The top quartile of indexed LV mass and concentricity were 35.8 g/m(2.7) or higher and 1.5 g/ml or higher, respectively. History of rejection (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.1-16.4; p < 0.01), diabetes (OR, 3.3; 95% CI, 1.3-8.2; p = 0.01), and post-transplant year of MRI acquisition (OR, 1.2; 95% CI, 1.1-1.4; p < 0.01) were associated with the top quartile of LV mass in multivariable models. LV mass and concentricity were independently associated with cardiovascular death (hazard risk [HR], 1.11 per g/m;(2.7) HR, 10.1 per g/ml, p ≤ 0.01, respectively). LV concentricity was independently associated with all-cause mortality (HR, 4.4 per g/ml, p < 0.01). CONCLUSION A history of rejection and diabetes are associated with increased LV mass. Increased LV mass, particularly of a concentric phenotype, is an independent risk factor for cardiovascular and all-cause mortality after HTx.

Bendopnea and risk of adverse clinical outcomes in ambulatory patients with systolic heart failure.

Background Recently, the symptom of bendopnea, that is, shortness of breath when bending forwards such as when putting on shoes, has been described in heart failure patients and found to be associated with higher ventricular filling pressures, particularly in the setting of low cardiac index. However, it is not known whether bendopnea is associated with clinical outcomes. Methods In a prospective convenience sample of 179 patients followed in our heart failure disease management clinic, we determined the presence of bendopnea at the time of enrollment and ascertained clinical outcomes through 1 year of follow‐up. We performed univariate and stepwise multivariable modeling to test the association of bendopnea with clinical outcomes. Results Bendopnea was present in 32 of 179 (18%) subjects. At 1 year, those with versus without bendopnea were at increased risk of the composite endpoint of death, heart failure admission, inotrope initiation, left ventricular assist device implantation, or cardiac transplantation in univariate (hazard ratio [HR] 1.9, P < .05) but not multivariable (HR 1.9, P = .11) analysis. Bendopnea was more strongly associated with short‐term outcomes including heart failure admission at 3 months in both univariate (HR 3.1, P < .004) and multivariable (HR 2.5, P = .04) analysis. Conclusions Bendopnea was associated with an increased risk of adverse outcomes in ambulatory patients with heart failure, particularly heart failure admission at 3 months.

Implantation of a left ventricular assist device to provide long-term support for end-stage Duchenne muscular dystrophy-associated cardiomyopathy

A young man with Duchenne muscular dystrophy presented to the UT Southwestern Neuromuscular Cardiomyopathy Clinic with advanced heart failure. Despite maximal medical therapy, his cardiac function continued to decline requiring initiation of inotrope therapy. Given the patients clinical deterioration, a left ventricular assist device (LVAD) was implanted as destination therapy after undergoing a multidisciplinary assessment. The patient tolerated the surgical implantation of the LVAD without any significant complications, and he has had a relatively unremarkable course 38 months post‐LVAD implantation. A critical factor contributing to the long‐term success of this patient was the decision to select an LVAD that would not disrupt the diaphragm and thus preserve the respiratory muscle strength. This case demonstrates that permanent mechanical LVADs should be considered for appropriately selected Duchenne muscular dystrophy patients with medically refractory end‐stage cardiomyopathy.

Predictors of Death in Adults With Duchenne Muscular Dystrophy–Associated Cardiomyopathy

Background Duchenne muscular dystrophy (DMD) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to DMD patients over the past 2 decades, there remains a group of DMD patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult DMD patients. Methods and Results A retrospective cohort of 43 consecutive patients was followed in the adult UT Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The DMD population was in the early 20s, with median follow‐up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin‐converting enzyme inhibitors (86%) and steroids (56%), but few other guideline‐directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8–19.3] versus 25.8 [20.8–29.1] kg/m2, P<0.01), alanine aminotransferase levels (26 [18–42] versus 53 [37–81] units/L, P=0.001), maximum inspiratory pressures (13 [0–30] versus 33 [25–40] cmH2O, P=0.03), and elevated cardiac biomarkers (N‐terminal pro‐brain natriuretic peptide: 288 [72–1632] versus 35 [21–135] pg/mL, P=0.03]. Conclusions The findings demonstrate a DMD population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high‐risk cardiovascular population with a worse prognosis.

CARDIAC ATROPHY: A NOVEL MECHANISM FOR DUCHENNE MUSCULAR DYSTROPHY (DMD)-ASSOCIATED CARDIOMYOPATHY

Objective: To define the cardiac phenotype and unique maladaptive cardiac remodeling that occurs in the Duchenne muscular dystrophy population. Background: DMD-associated cardiomyopathy is the primary cause of death in DMD, but the mechanism has not been well characterized. In DMD, skeletal muscle degeneration and atrophy occurs. Therefore, we hypothesize that cardiac remodeling occurs secondary to cardiac atrophy rather than pathological cardiac hypertrophy leading to dilated cardiomyopathy. We compared MRI derived parameters between DMD, non-ischemic cardiomyopathy (NICM) patients and healthy controls from the Dallas Heart Study (DHS). Design/Methods: Demographic data and cardiac MRI parameters were collected via retrospective chart review on 20 DMD patients, 20 age, weight- and sex-matched patients with NICM and 40 age, weight- and sex-matched DHS patients. Results: DMD patients had a significantly lower LV mass index as compared to NICM patients (Figure: 54.8 ± 3.4 vs 85 ± 0.07, p p p p p =0.002, normal: 67 ± 5%) and the DMD population had a lower LVEF when compared with the DHS control (50 ± 3 vs 65 ± 0.01, p Conclusions: DMD patients have significantly lower LV mass index as compared to subjects with NICM, suggesting that cardiac atrophy may be a potential mode of cardiac remodeling. These data identify a novel pathophysiologic mechanism of DMD-associated cardiomyopathy. Disclosure: Dr. Khan has nothing to disclose. Dr. Cheeran has nothing to disclose. Dr. Mammen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with OAR/D-OAR Registy (CareDx Inc), PhaseBio, Catabasis, Heartware. Dr. Mammen has received personal compensation in an editorial capacity for AHA Innovative Research Grant Committee, California Institute of Regenerative Medicine Grant Review Committee.

Induction regimen and survival in simultaneous heart-kidney transplant recipients

BACKGROUND Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). METHODS We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up. RESULTS During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). CONCLUSION r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge.