Sabha Bhatti

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

Background— Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. Methods and Results— We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15±0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score≥4). Ischemia was defined as a summed stress score ≥4 plus a summed difference score ≥2, and scar was defined as a summed difference score <2 plus a summed stress score ≥4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL · min−1 · 1.73 m−2) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global &khgr;2 207.5 versus 169.3, P<0.0001). Conclusions— MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

Effectiveness of Percutaneous Coronary Intervention With Drug-Eluting Stents Compared With Bypass Surgery in Diabetics With Multivessel Coronary Disease: Comprehensive Systematic Review and Meta-analysis of Randomized Clinical Data

Background Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). Coronary artery bypass grafting (CABG) has been compared with percutaneous coronary intervention (PCI) using drug‐eluting stents (DES) in recent randomized controlled trials (RCTs). Methods and Results RCTs comparing PCI with DES versus CABG in diabetic patients with MVD who met inclusion criteria were analyzed (protocol registration No. CRD42013003693). Primary end point (major adverse cardiac events) was a composite of death, myocardial infarction, and stroke at a mean follow‐up of 4 years. Analyses were performed for each outcome by using risk ratio (RR) by fixed‐ and random‐effects models. Four RCTS with 3052 patients met inclusion criteria (1539 PCI versus 1513 CABG). Incidence of major adverse cardiac events was 22.5% for PCI and 16.8% for CABG (RR 1.34, 95% CI 1.16 to 1.54, P<0.0001). Similar results were obtained for death (14% versus 9.7%, RR 1.51, 95% CI 1.09 to 2.10, P=0.01), and MI (10.3% versus 5.9%, RR 1.44, 95% CI 0.79 to 2.6, P=0.23). Stroke risk was significantly lower with DES (2.3% versus 3.8%, RR 0.59, 95% CI 0.39 to 0.90, P=0.01) and subsequent revascularization was several‐fold higher (17.4% versus 8.0%, RR 1.85, 95% CI 1.0 to 3.40, P=0.05). Conclusions These data demonstrate that CABG in diabetic patients with MVD at low to intermediate surgical risk (defined as EUROSCORE <5) is superior to MVD PCI with DES. CABG decreased overall death, nonfatal myocardial infarction, and repeat revascularization at the expense of an increase in stroke risk.

Safety and efficacy of drug eluting stents compared with bare metal stents for saphenous vein graft interventions: A comprehensive meta-analysis of randomized trials and observational studies comprising 7,994 patients†

Background: Saphenous vein graft (SVG) lesions remain amongst the most challenging lesions for percutaneous coronary intervention (PCI). It is unknown whether drug eluting stents (DES) are superior to bare metal stents (BMS) for such lesions. Our objective is to determine the safety and efficacy of DES compared with BMS for SVG lesions by performing a meta‐analysis of clinical trials and observational studies. Data Sources: PubMed, Cochrane Register of Controlled Trials, conference proceedings, and internet‐based resources of clinical trials. Study Selection:Studies comparing DES vs. BMS for SVG lesions with at least > 30 patients in each study reporting the outcomes of interest [death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), and the composite of death, TVR and MI (major adverse cardiac events; MACE)] with at least 6 months clinical follow‐up. The primary outcome of interest was death. Results:Two randomized trials, one subgroup analysis of a randomized trial and 26 observational studies comprising a total of 7,994 patients (4,187 patients in DES and 3,807 patients in BMS group) were included in the analysis .Mean follow‐up duration was 21 ± 11 months (6–48 months). In the overall population, MACE events were 19% in DES and 28% in BMS with a risk ratio (RR) of 0.7 (0.6, 0.8) P < 0.00001. This effect of MACE was sustained in studies with >2 years follow‐up with RR of 0.77 (0.65, 0.91) P = 0.003. Death rate was 7.8% in DES and 9% in BMS with a RR of 0.82 (0.7, 0.97) P = 0.02. MI rate was 5.7% in DES and 7.6% in BMS with RR of 0.72 (0.57, 0.91) P = 0.007. TVR was 12% in DES and 17% in BMS with RR of 0.71 (0.59, 0.85) P = 0.0002. ST was 1% in DES and 1.7 % in BMS RR of 0.61 (0.35, 1.06) P = 0.08. Specifically in randomized controlled trials, DES were associated with no significant differences in overall mortality [RR = 1.97; 95% confidence interval (CI), 0.17–23; P = 0.58] or MI (RR = 1.24; 95% CI, 0.3–5.5; P = 0.78) compared with BMS. Conclusions:Based on the results of this meta‐analysis, DES may be considered as a safe and efficacious option for the percutaneous intervention of SVG lesions.

Severe acute fibrinous and organizing pneumonia (AFOP) causing ventilatory failure: Successful treatment with mycophenolate mofetil and corticosteroids

Acute fibrinous and organizing pneumonia (AFOP) has recently been identified as an unusual variant of acute lung injury. We describe a man with rapidly progressive lung disease who had AFOP detected via surgical lung biopsy. The patient acutely decompensated while in the hospital and required mechanical ventilation as well as a prolonged ICU stay. He responded poorly to initial treatment and progressively worsened, but he subsequently responded very well to combined therapy with mycophenolate mofetil and methylprednisolone. The combination of corticosteroids and mycophenolate may provide a safe and effective treatment strategy for severe forms of this newly defined pulmonary syndrome.

The Spectrum of Atherosclerotic Coronary Artery Disease in HIV Patients

The incidence of HIV is on the rise. With the advent of antiretroviral therapy, the average life expectancy of HIV patients has increased by several decades, but the increasing life expectancy has shifted the spectrum of HIV-associated morbidity and mortality away from opportunistic infections and toward chronic medical conditions. In fact, coronary artery disease has become the leading cause of mortality in patients with HIV. The pathophysiology of atherosclerosis in patients with HIV is very complex, including direct endothelial damage from viremia, a heightened overall state of inflammation from immune activation, higher prevalence and contribution from traditional atherosclerotic risk factors, and direct effects from antiretroviral therapy itself. This review focuses on the patterns, predictors, and pathophysiology of atherosclerotic disease in patients with HIV. In addition, the risks and benefits of evidence-based highly active antiretroviral therapy are critically evaluated.

Renal Function and Risk Stratification of Diabetic and Nondiabetic Patients Undergoing Evaluation for Coronary Artery Disease

OBJECTIVES The aim of this study was to evaluate the impact of renal function by estimated glomerular filtration rate (eGFR) on risk stratification of diabetic and nondiabetic patients undergoing myocardial perfusion imaging (MPI) by single-photon emission computed tomography for suspected ischemia. BACKGROUND Coronary artery disease is the leading cause of death among diabetic persons; however, diabetic persons are a very heterogeneous group in terms of cardiovascular risk, necessitating further risk stratification. METHODS Patients (n = 1,747, age 65 +/- 10 years, 37% diabetic) undergoing MPI were followed for cardiac death (CD) for a mean of 2.15 +/- 0.8 years. Chronic kidney disease (CKD) was defined by an eGFR <60 ml/min. RESULTS In the presence of a normal scan, annual CD rate was 0.9% for those with no diabetes mellitus (DM) and no CKD, 0.5% in the DM alone group, 2.35% in CKD alone, and 2.9% in those with both DM and CKD (p < 0.001). Patients with DM+CKD had a 2.7-fold risk of CD compared with no DM no CKD (p = 0.001) after controlling for age, ejection fraction, history of coronary artery disease, and other risk factors. The risk of CD increased as a function of the presence and severity of perfusion defects, regardless of CKD or DM status. Presence of CKD conferred a several-fold higher risk of CD for the various strata of perfusion defects. Log-rank test for difference in probability of CD was nonsignificant for comparison between patients with no DM no CKD and those with DM alone (p = 0.73) but was significant for comparison between patients with no DM no CKD and patients with CKD alone (p < 0.001) or DM+CKD (p < 0.001). CONCLUSIONS MPI and eGFR provide valuable risk stratification for diabetic and nondiabetic patients. Diabetic patients without CKD seem to have similar short-term cardiac outcomes compared with nondiabetic patients. Underlying CKD seems to identify a high-risk subgroup of diabetic patients.

Coronary computed tomography angiography.

PURPOSE OF REVIEW Significant limitations exist for traditional noninvasive cardiac imaging with regard to equivocal or indeterminate findings that result in repetitive testing or unnecessary referral to invasive coronary angiography (ICA). Recent hardware and software advances in multislice computed tomography angiography have achieved high spatial and temporal resolution to allow accurate noninvasive assessment of coronary arteries. This poses a paradigm shift in management of patients with suspected coronary artery disease (CAD). RECENT FINDINGS Multicenter studies showed that coronary computed tomography angiography (CCTA) has a very high diagnostic accuracy, and, in particular, a very high negative predictive value (>98%) in detecting coronary stenosis when compared with ICA. In addition to its diagnostic ability, recent evidence-based outcome data have also validated the value of CCTA in predicting cardiac events. Absence of CAD on CCTA conveys excellent prognosis, whereas increasing disease severity and extent are associated with worsening outcome. Furthermore, CCTA allows comprehensive assessment of coronary stenosis, plaque burden, left ventricular morphology, function, perfusion and viability. One concern with CCTA is the issue of ionizing radiation exposure. Recent technical progress allows dramatic reduction of radiation dose. The newest generation scanner is capable of producing CCTA of diagnostic quality with a dose of less than 1 mSv. A multisociety guideline for appropriate clinical indications for cardiac computed tomography was recently published. SUMMARY When used appropriately, CCTA has been established as a valid noninvasive imaging alternative to ICA in selected patients at low to intermediate risk of CAD.

Clinical and prognostic utility of cardiovascular magnetic resonance imaging in myeloma patients with suspected cardiac amyloidosis

OBJECTIVES AL amyloidosis affects up to 30% of patients with multiple myeloma (MM), and cardiac involvement is associated with worse outcomes. Traditional screening modalities including EKG, echocardiography and biomarkers have limited value. The aim of this study was to evaluate the clinical and prognostic value of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging in patients with plasma cell dyscrasias and suspected cardiac amyloidosis (CA). METHODS A total of 251 consecutive patients with plasma cell dyscrasias who underwent CMR were enrolled in this study. Primary endpoint was all cause mortality. Clinical, ECG, echocardiographic, biomarker and CMR predictors of mortality were analyzed. RESULTS Mean age of population was 63 ± 10 years, 36% females and 19% African Americans. During a median follow-up duration of 28 months (IQR 5-56), there were 97 deaths (39%). Patients who died were more likely to have diabetes (28% vs. 14%; P = 0.03), CAD (28% vs. 16%; P = 0.04) and CKD (33% vs. 21%; P = 0.04). With endomyocardial biopsy as the gold standard (42 (17%) patients), amyloid pattern on CMR (LGE+) had sensitivity and negative predictive values of 100%; specificity and positive predictive values of 80 and 81% with an AUC 0.9 for CA. History of CAD (HR 1.64, 95% CI 1.01-2.6; P = 0.04), brain natriuretic peptide (HR 1.0003 95% CI 1.0001-1.0006; P = 0.004) and LGE + (HR 1.72, 95% CI 1.05-2.8; P = 0.02) were independent predictors of mortality. LGE+ possessed incremental prognostic value over clinical, laboratory and echocardiographic variables for mortality prediction. CONCLUSIONS CMR is a clinically useful tool for diagnosis and prognostication in myeloma patients with suspected CA.

Lp-PLA2 as a Marker of Cardiovascular Diseases

Inflammation lies at the base of endothelial dysfunction, eventually leading to plaque formation. The degree of inflammation defines the “vulnerability” of plaque to rupture. Numerous strategies have been adopted to identify and eventually treat high-risk vulnerable plaque. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as one such candidate marker of inflammation that may play a direct role in the formation of rupture-prone plaque. Epidemiologic studies have clearly demonstrated the prognostic ability of increased Lp-PLA2 levels and their association with increased risk of future coronary and cerebrovascular events. Moreover, Lp-PLA2 might have similar predictive power for both incident coronary heart disease in initially healthy individuals as well as for recurrent events in those with clinically manifest atherosclerosis. The latest evidence has also suggested its incremental value for risk determination over the well-established traditional risk factors and biomarkers in patients with congestive heart failure. These data support an integral role of Lp-PLA2 activity in lipid peroxidation and cardiovascular risk assessment. This review summarizes the current body of evidence supporting the clinical utility of Lp-PLA2 and its future applications in cardiovascular medicine.

Clinical and prognostic value of poststenting fractional flow reserve in acute coronary syndromes

Objectives Fractional flow reserve (FFR) has been suggested to have value in acute coronary syndromes (ACSs). The clinical and prognostic value of ischaemia reduction assessed by post-percutaneous coronary intervention (PCI) FFR has not been studied in this population. Methods Consecutive stable ischaemic heart disease (SIHD) (N=390) and patients with ACS (N=189) who had pre-PCI FFR and post-PCI FFR were followed for 2.4±1.5 years. Primary endpoint was major adverse cardiac events (MACE) (composite of myocardial infarction, target vessel revascularisation and death). Results In patients with ACS, PCI led to significant improvement in FFR from 0.62±0.15 to post-PCI FFR 0.88±0.08 (p<0.0001). Post-PCI FFR identified 29 patients (15%) who had persistently low FFR<0.80 (0.75±0.06) despite angiographically optimal results prompting subsequent interventions improving repeat FFR (0.85±0.06; p<0.0001). The difference in MACE events between patients with ACS and patients with SIHD varied according to the post-PCI FFR value (interaction p=0.044). Receiver operator curve analysis identified a final FFR cut-off of ≤0.91 as having the best predictive accuracy for MACE in the ACS study population (30% vs 19%; p=0.03). Patients with ACS achieving final FFR of >0.91 had similar outcomes compared with patients who had SIHD (19% vs 16%; p=0.51). However, in patients with final FFR of ≤0.91 there was increased MACE versus patients with SIHD (30% vs 16%; p<0.01). Conclusions Post-PCI FFR is valuable in assessing the functional outcome of PCI in patients with ACS. Use of post-PCI FFR in patients with ACS allows for functional optimisation of PCI results and is predictive of long-term outcomes in patients with ACS.