Myopathy Associated With Statins and SGLT2 - A Review of Literature.

Drug-induced myopathy is a well-described clinical entity characterized by muscle damage leading to symptoms ranging from myalgias to rhabdomyolysis and acute kidney injury. Many pharmacotherapies are known to precipitate myopathic symptoms. Recent case reports suggest a potential relationship between the use of sodium/glucose cotransport 2 (SGLT2) inhibitors and onset of myopathy. The pathogenesis of this has yet to be elucidated. The relevance of this association is augmented by the recent popularity of SGLT2 inhibitors as well as the tendency for them to be prescribed alongside statins. This study reviewed the literature on the incidence and mechanism of drug-induced myopathy in patients with type 2 diabetes mellitus who are taking SGLT2 inhibitors with and without the use of statins.

Ventricular Septal Aneurysm Mimicking Right Ventricular Outflow Tract Mass in a Patient With Ventricular Septal Defect.

A 50-year-old man presented with an episode of chest pain. Cardiac magnetic resonance revealed the presence of a large ventricular septal aneurysm partially closing a perimembranous ventricular septal defect, prolapsing into the right ventricular outflow tract, and mimicking a mass. We illustrate the diagnostic approach and management of such ventricular septal aneurysms. (Level of Difficulty: Advanced.).

Trends in the use of echocardiography in pulmonary embolism.

Pulmonary embolism (PE) is a devastating diagnosis which carries a high mortality risk. Echocardiography is often performed to risk stratify patients diagnosed with PE, and guide management strategies. Trends in the performance of echocardiography among patients with PE and its role in influencing outcomes is unknown.We analyzed the 2005 to 2014 National Inpatient Sample Database to identify patients with primary diagnosis of PE or secondary diagnosis of PE and ≥1 of the following diagnoses: syncope, thrombolysis, acute deep vein thrombosis, acute cardiorespiratory failure, and secondary pulmonary hypertension. Trends in the performance of echocardiography and in-hospital mortality were analyzed. The admissions were divided into 2 groups with echocardiography, and without echocardiography, and 1:2 propensity score matching (PSM) was performed for comparison. The primary end-point was in-hospital mortality. The secondary endpoints were length of stay and total hospitalization costs. Odd ratios (OR) with confidence intervals (CI) were reported.A total of 299,536 unweighted PE cases were studied. Performance of echocardiography among patients with PE patients increased from 3.5% to 5.6%, whereas in-hospital mortality decreased from 4.2% to 3.7% between years 2005 and 2014. Before matching, patients who received an echocardiogram were more likely to be younger, African American, admitted to a large, urban teaching institute, and had higher rates of concurrent acute deep vein thrombosis, and acute respiratory failure. Post-PSM, patients who received echocardiography during hospitalization had lower in-hospital mortality (odds ratio 0.75, 95% confidence intervals (CI) 0.68-0.83; P < 0.001), longer length of stay (median 6 days vs 5 days; P < .001) and higher mean hospitalization costs ($34,379 vs $27,803; P < .001) compared to those without echocardiography.Performance of echocardiography among patients with a PE is increasing and is associated with lower in-hospital mortality.

Acute kidney injury requiring dialysis and in-hospital mortality in patients with chronic kidney disease and non-ST-segment elevation acute coronary syndrome undergoing early vs delayed percutaneous coronary intervention: A nationwide analysis.

BACKGROUND: Chronic kidney disease (CKD) is a well-known risk factor for coronary artery disease and is associated with poor outcomes following an acute coronary syndrome (NSTE-ACS). The optimal timing of an invasive strategy in patients with CKD and NSTE-ACS is unclear. HYPOTHESIS: Timing of PCI in CKD patients will not affect the risk of mortality or incidence of dialysis. METHODS: We queried the National Inpatient Sample database (NIS) to identify cases with NSTEMI and CKD. Patients who underwent percutaneous coronary intervention (PCI) day 0 or 1 vs day 2 or 3 after admission were categorized as early vs delayed PCI, respectively. The primary outcomes of the study were in-hospital mortality and acute kidney injury requiring hemodialysis (AKI-D). The secondary outcomes were length of stay and hospital charges. Baseline characteristics were balanced using propensity score matching (PSM). RESULTS: After PSM, 3708 cases from the delayed PCI group were matched with 3708 cases from the early PCI group. The standardized mean differences between the 2 groups were substantially reduced after PSM. All other recorded variables were balanced between the 2 groups. In the early and delayed PCI groups, the incidence of AKI-D (2.5% vs 2.3%; P = 0.54) and in-hospital mortality (1.9% vs 1.4%; P = 0.12) was similar. Hospital charges and length of stay were higher in the delayed PCI group. CONCLUSIONS: The incidence of AKI-D and in-hospital mortality among patients with CKD and NSTE-ACS were not significantly affected by the timing of PCI. However, delayed PCI added significant cost and length of stay. A prospective randomized study is required to validate this concept.

Percutaneous coronary intervention and inpatient mortality in patients with advanced chronic kidney disease presenting with acute coronary syndrome.

Chronic kidney disease (CKD) is an important risk factor for coronary artery disease, yet patients with CKD are less likely to undergo coronary angiography and percutaneous coronary intervention (PCI). We retrospectively analyzed the 2006-2012 National Inpatient Sample Database to examine the temporal trends in coronary angiography and PCI among patients without CKD, with advanced CKD (CKD III-V), and with end-stage renal disease (ESRD) presenting with unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and ST-elevation myocardial infarction (STEMI). A total of 579,747 admissions for NSTE-ACS and 293,950 admissions for STEMI were studied. Patients with NSTE-ACS were less likely to undergo coronary angiography/PCI than those with STEMI, irrespective of CKD. Between 2006 and 2012, performance of PCI saw an uptrend across all CKD groups with NSTE-ACS (no CKD, 29.9%-36.8%; CKD III-V, 18.2%-21.5%; ESRD, 19.8%-27.5%; all Ptrends < 0.01) and STEMI (no CKD, 57.0%-76.0%; CKD III-V, 33.0%-52.6%; ESRD, 29.9%-42.9%; Ptrends < 0.01). Multivariate analyses revealed that PCI was associated with a lower risk of hospital mortality across all degrees of CKD in both NSTE-ACS (adjusted odds ratios: no CKD, 0.44; CKD III-V, 0.48; ESRD, 0.46; P < 0.01) and STEMI (no CKD, 0.35; CKD III-V, 0.50; ESRD, 0.52; P < 0.01). Performance of PCI increased over time among patients presenting with NSTE-ACS and STEMI in the presence of advanced CKD and independently predicted lower in-hospital mortality.

Evaluating safety of thrombolysis in chronic kidney disease patients presenting with pulmonary embolism using propensity score matching.

To assess the safety of thrombolytic therapy in chronic kidney disease (CKD) patients who present with pulmonary embolism (PE). We used the Nationwide Inpatient Sample Database to identify patients who underwent thrombolysis for PE between 2010 and 2014. The patients were divided into two groups: (1) No CKD and (2) CKD. Patients with and without CKD were matched using 1:1 propensity score matching and a caliper width of 0.01. The primary outcomes were in-hospital mortality and hemorrhagic events. The secondary outcomes were blood transfusions, length of stay and total hospitalization charge. Two separate, multivariate analyses were also performed to determine the predictors for primary outcomes. The No CKD group had 16,238 and CKD group had 1341 patients prior to matching. Patients with CKD were older (Median age 67 vs. 57 years; p < 0.01), male (60.6 vs. 51.8%) and had a higher prevalence of coronary artery disease, congestive heart failure, diabetes, hyperlipidemia, hypertension, and prior stroke among other comorbidities. They also had significantly higher rate of in-hospital mortality (OR 1.66) and hemorrhagic events (OR 1.47) prior to matching. Post-matching, there was no difference in hospital mortality (22.9 vs. 21.8%; p = 0.51) or hemorrhagic events (3.8 vs. 3.0%; p = 0.27) between CKD and No CKD groups. Patients with CKD had a longer length of stay, but no difference in proportion of patients receiving a blood transfusion and total hospitalization charges post-matching. Multivariate analysis showed that CKD did not predict mortality (OR 0.88, 0.75-1.02; p = 0.09) or hemorrhagic events (OR 0.89, 95% CI 0.76-1.04; 0.13). There was no increase in rate of hospital mortality or hemorrhagic events among CKD patients who underwent thrombolysis for PE.

Red cell distribution width and risk of cardiovascular mortality: Insights from National Health and Nutrition Examination Survey (NHANES)-III.

INTRODUCTION: Red cell distribution width (RDW) has been linked to cardiovascular disease. We sought to determine whether addition of RDW improved the Framingham risk score (FRS) model to predict cardiovascular mortality in a healthy US cohort. METHODS: We performed a post-hoc analysis of the National Health and Nutritional Examination Survey-III (1988-94) cohort, including non-anemic subjects aged 30-79years. Primary endpoint was death from coronary heart disease (CHD). We divided the cohort into three risk categories: <6%, 6-20% and >20%. RDW>14.5 was considered high. Kaplan-Meier survival curves and Cox proportional hazards models were created. Discrimination, calibration and reclassification were used to assess the value of addition of RDW to the FRS model. RESULTS: We included 7005 subjects with a mean follow up of 14.1years. Overall, there were 233 (3.3%) CHD deaths; 27 (8.2%) in subjects with RDW>14.5 compared to 206 (3.1%) in subjects with RDW≤14.5 (p<0.001). Adjusted hazard ratio of RDW in predicting CHD mortality was 2.02 (1.04-3.94, p=0.039). Addition of RDW to FRS model showed significant improvement in C-statistic (0.8784 vs. 0.8751, p=0.032) and area under curve (0.8565 vs. 0.8544, p=0.05). There was significant reclassification of FRS with a net reclassification index (NRI) of 5.6% (p=0.017), and an intermediate-risk NRI of 9.6% (p=0.011). Absolute integrated discrimination index (IDI) was 0.004 (p=0.02), with relative IDI of 10.4%. CONCLUSIONS: Our study demonstrates that RDW is a promising biomarker which improves prediction of cardiovascular mortality over and above traditional cardiovascular risk factors.

Influence of Pregnancy in Patients With Congenital Long QT Syndrome.

Congenital long QT syndrome (LQTS) is a disorder of myocardial repolarization and is characterized by a prolonged QT interval on an electrocardiogram. A prolonged QT predisposes patients to an increased risk of syncope and sudden cardiac death secondary to polymorphic ventricular tachycardia. Several mutations linked to the LQTS have been identified, the most common of which have been found in the potassium channel KCNQ1 (LQT1) and hERG (LQT2) genes and in the sodium channel SCN5A (LQT3) gene. Female sex is an independent risk factor for the development of torsades de pointes in LQTS. Furthermore, although pregnancy may be associated with protection against cardiac events in LQTS, the 9-month postpartum period represents a time of increased arrhythmogenicity. Interestingly, these cardiac events during the postpartum period are more common in patients with LQT2. The precise mechanisms that influence the cardiac repolarization during the postpartum period are unclear. Beta-blockers are considered reasonably safe during pregnancy and should be continued or initiated in patients with LQTS to reduce the risk of cardiac events. Implantable cardioverter defibrillators are safe in pregnancy, and there is no evidence that pregnant women with these devices are at any greater risk for adverse complications solely on the grounds of having the device.

A complete heart block in a young male: a case report and review of literature of cardiac sarcoidosis.

Cardiac sarcoidosis is one of the uncommon causes of heart failure. Generally, it presents in the form of varying clinical manifestations ranging from asymptomatic to fatal arrhythmias such as ventricular tachycardia and complete heart block. It is difficult to make a diagnosis strictly based on clinical grounds. However, in the setting of extracardiac sarcoidosis and patients presenting with advanced heart block or ventricular arrhythmia, direct cardiac involvement should be suspected. The definitive diagnosis of cardiac sarcoidosis can be made from endomyocardial biopsy, but it is falling out of favor due to patchy myocardial involvement, considerable procedure-related risks, and advancement in additional imaging modalities. Once cardiac sarcoidosis has been diagnosed, management of the disease remains challenging. Steroids are considered the mainstay of therapy, and implantable cardioverter defibrillator therapy can be considered in a selected group of patients at greater risk for malignant ventricular arrhythmias.

Comparative accuracy of supine-only and combined supine-prone myocardial perfusion imaging in men.

BACKGROUND: Combined supine-prone myocardial perfusion imaging (CSP MPI) has been shown to reduce attenuation artifact in comparison to supine-only (SU) MPI in mixed-gender populations with varying risk for coronary artery disease (CAD), often where patients served as their own controls. However, there is limited direct comparison of these imaging strategies in men. METHODS: 934 male patients underwent CSP or SU MPI. Diagnostic certainty of interpretation was compared. Within the cohort, 116 were referred for left heart catheterization (LHC) to assess for CAD. Sensitivity, specificity, and area under the curve (AUC) were compared with additional analysis based on body mass index (BMI). RESULTS: 597 patients completed the SU protocol and 337 patients completed the CSP protocol. Equivocal studies were seen more frequently in the SU group (13%) than in the CSP group (4%, P < .001). At catheterization, the specificity for CSP MPI of 70% was higher than 40% for SU MPI (P = .032). The CSP AUC (0.80 ± 0.06) was significantly larger than SU AUC (0.57 ± 0.05, P = .004). CSP specificity was significantly higher in obese patients. CONCLUSIONS: CSP MPI increases diagnostic certainty and improves test accuracy for CAD detection in men with CAD risk factors, especially obese patients, compared to SU MPI.

Metrics of quality care in veterans: correlation between primary-care performance measures and inappropriate myocardial perfusion imaging.

BACKGROUND: Approximately 10% to 20% of myocardial perfusion imaging (MPI) tests are inappropriate based on professional-society recommendations. The correlation between inappropriate MPI and quality care metrics is not known. HYPOTHESIS: Inappropriate MPI will be associated with low achievement of quality care metrics. METHODS: We conducted a retrospective cross-sectional investigation at a single Veterans Affairs medical center. Myocardial perfusion imaging tests ordered by primary-care clinicians between December 2010 and July 2011 were assessed for appropriateness (by 2009 criteria). Using documentation of the clinical encounter where MPI was ordered, we determined how often quality care metrics were achieved. RESULTS: Among 516 MPI patients, 52 (10.1%) were inappropriate and 464 (89.9%) were not inappropriate (either appropriate or uncertain). Hypertension (82.2%), diabetes mellitus (41.3%), and coronary artery disease (41.1%) were common. Glycated hemoglobin levels were lower in the inappropriate MPI cohort (6.6% vs 7.5%; P = 0.04). No difference was observed in the proportion with goal hemoglobin (62.5% vs 46.3% for appropriate/uncertain; P = 0.258). Systolic blood pressure was not different (132 mm Hg vs 135 mm Hg; P = 0.34). Achievement of several other categorical quality metrics was low in both cohorts and no differences were observed. More than 90% of clinicians documented a plan to achieve most metrics. CONCLUSIONS: Inappropriate MPI is not associated with performance on metrics of quality care. If an association exists, it may be between inappropriate MPI and overly aggressive care. Most clinicians document a plan of care to address failure of quality metrics, suggesting awareness of the problem.

Clinical utility of inappropriate positron emission tomography myocardial perfusion imaging: test results and cardiovascular events.

BACKGROUND: Appropriate use criteria for myocardial perfusion imaging (MPI) were developed to categorize scenarios where MPI might be beneficial (appropriate) or not (inappropriate). Few investigations have evaluated the clinical utility of this categorization strategy, particularly with positron emission tomography (PET) MPI. METHODS AND RESULTS: We conducted this retrospective cohort investigation in a Veterans Affairs (VA) medical center, on predominantly male subjects who underwent PET-MPI. We correlated appropriateness to test result and cardiovascular events. Of 521 subjects, 414 (79.5%) were appropriate, 54 (10.4%) were uncertain, and 53 (10.2%) were inappropriate. PET-MPI was abnormal more often when appropriate or uncertain (28% and 34.6%, respectively, vs 7.7% for inappropriate, P = .003). Among abnormal inappropriate tests, none detected occult ischemia. By Cox regression, summed difference score ≥5 (HR 5.06, 95% CI 2.72-9.44) and an abnormal test result (HR 4.48, 95% CI 2.19-9.14) were associated with higher likelihood of catheterization. Log-rank analysis demonstrated similar likelihood of catheterization when comparing abnormal vs normal test result (P < .0001) and between appropriate, uncertain, and inappropriate tests (P = .024). CONCLUSIONS: Inappropriate PET-MPI was rarely abnormal, associated with low catheterization rates, and failed to detect occult ischemia for any subjects. The clinical utility of inappropriate PET-MPI is negligible.

Clinician-dependent variations in inappropriate use of myocardial perfusion imaging: training, specialty, and location.

BACKGROUND: Inappropriate use of myocardial perfusion imaging (MPI) may vary depending on the training, specialty, or practice location of the clinician. METHODS: We conducted a cross-sectional investigation of consecutive patients who underwent MPI at our Veterans Affairs medical center between December 2010 and July 2011. Characteristics of the MPI ordering clinicians were extracted to investigate any associations with inappropriate use. RESULTS: 582 patients were included, 9.8% were inappropriate. No difference in inappropriate use was observed between cardiology and non-cardiology clinicians (n = 21, 9.5% vs n = 36, 10.0%, P = .83); no difference was noted between nurse practitioners/physician assistants, attending physicians, and housestaff (7.5% vs 11.2% vs 1.8%, P = .06). Comparing inpatient, emergency department and outpatient clinician groups, the difference was null (8.6% vs 6.3% vs 10.1%, P = .75). For most clinician groups, the most common inappropriate indication was an asymptomatic scenario; however, some groups were different: definite acute coronary syndrome for inpatient clinicians and low risk syncope for emergency medicine clinicians. CONCLUSIONS: Clinician groups appear to order inappropriate MPI at similar rates, regardless of their training, specialty, or practice location. Differences in the most common type of inappropriate testing suggest that interventions to reduce inappropriate use should be tailored to specific clinician types.

Pulmonary hypertension in hypertensive patients: association with diastolic dysfunction and increased pulmonary vascular resistance.

BACKGROUND: Pulmonary hypertension (PH) in patients with systemic hypertension and preserved ejection fraction (PEF) has been described. However, the pathophysiology and consequences are not entirely clear. We sought to distinguish the clinical and anatomic features among hypertensive patients with or without coexistent PH. METHODS: Echocardiograms and records of hypertensive patients with left ventricular (LV) hypertrophy and PEF from January 2009 to January 2011 were reviewed. We identified 174 patients, including 36 with PH (calculated pulmonary artery systolic pressure [PASP] ≥ 35 mmHg), and 138 with normal pulmonary pressures. RESULTS: Hypertensive patients with PH were older (76 ± 13 vs. 65 ± 13 years, P < 0.0001), more often female (91, 70%), had lower estimated glomerular filtration rate (eGFR) (63 ± 44 vs. 88 ± 48 mL/min, P = 0.002), and higher pro-BNP levels (3141 ± 4253 vs. 1219 ± 1900 pg/mL, P = 0.003). PH patients also had larger left atrial areas (23.7 ± 3.8 vs. 20.8 ± 4.6 cm(2) , P = 0.002), evidence of diastolic dysfunction (i.e., septal E/e' 17.6 ± 8.6 vs. 12.7 ± 4.4, P = 0.0005), and higher calculated peripheral vascular resistance (PVR) (2.3 ± 1.1 vs. 1.6 ± 0.4, P < 0.0001). Both PVR and septal E/e' showed strong linear correlation with PASP (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: Hypertension in elderly patients is frequently complicated by LV diastolic dysfunction and secondary PH. These hypertensive patients tended to have reduced renal function and higher pro-BNP. Because of the known morbidity and mortality associated with PH, these observations have potentially important implications for target medical therapy.

Estimation of right atrial and ventricular hemodynamics by CT coronary angiography.

BACKGROUND: Computed tomography coronary angiography (CTCA) provides an accurate noninvasive alternative to the invasive assessment of coronary artery disease. However, a specific limitation of CTCA is inability to assess hemodynamic data. OBJECTIVE: We hypothesized that CTCA-derived measurements of contrast within the superior vena cava (SVC) and inferior vena cava (IVC) would correlate to echocardiographic estimations of right atrial and right ventricular pressures. METHODS: Medical records of all patients who underwent both echocardiography and CTCA in our center were reviewed (n = 32). Standard CTCA was performed with a 64-detector CT using test-bolus method for image acquisition timing and iso-osmolar contrast injection through upper extremity vein. The length of the column of contrast reflux into the inferior vena cava (IVC) was correlated to echocardiographically determine tricuspid regurgitation jet velocity (TRV). SVC area change with contrast injection at the level of the bifurcation of the pulmonary artery was also correlated with IVC sniff response by echocardiogram. RESULTS: The reflux column length was interpretable in 27 of 32 patients with a mean length of 10.1 ± 1.1 mm, and a significant bivariate correlation was observed between reflux column length and the tricuspid regurgitant jet velocity (r = 0.84; P < .0001). Mean SVC distensibility ratio was 0.63 ± 0.03; mean IVC sniff response ratio was 0.53 ± 0.03. SVC distensibility correlated to IVC sniff response with a Pearson r of 0.57 (P = .04). CONCLUSION: Quantification of IVC and SVC contrast characteristics during CTCA provides a feasible and potentially accurate method of estimating right atrial and ventricular pressure.