Geoffrey Bergman

Angiogenesis Gene Therapy Phase I Assessment of Direct Intramyocardial Administration of an Adenovirus Vector Expressing VEGF121 cDNA to Individuals With Clinically Significant Severe Coronary Artery Disease

BACKGROUND Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Vascular Complications After Transcatheter Aortic Valve Replacement Insights From the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial

OBJECTIVES This study sought to identify incidence, predictors, and impact of vascular complications (VC) after transfemoral (TF) transcatheter aortic valve replacement (TAVR). BACKGROUND VC after TF-TAVR are frequent and may be associated with unfavorable prognosis. METHODS From the randomized controlled PARTNER (Placement of AoRTic TraNscathetER Valve) trial, a total of 419 patients (177 from cohort B [inoperable] and 242 from cohort A [operable high-risk]) were randomly assigned to TF-TAVR and actually received the designated treatment. First-generation Edwards-Sapien valves and delivery systems were used, via a 22- or 24-F sheath. The 30-day rates of major and minor VC (modified Valve Academic Research Consortium definitions), predictors, and effect on 1-year mortality were assessed. RESULTS Sixty-four patients (15.3%) had major VC and 50 patients (11.9%) had minor VC within 30 days of the procedure. Among patients with major VC, vascular dissection (62.8%), perforation (31.3%), and access-site hematoma (22.9%) were the most frequent modes of presentation. Major VC, but not minor VC, were associated with significantly higher 30-day rates of major bleeding, transfusions, and renal failure requiring dialysis, and with a significantly higher rate of 30-day and 1-year mortality. The only identifiable independent predictor of major VC was female gender (hazard ratio [HR]: 2.31 [95% confidence interval (CI): 1.08 to 4.98], p = 0.03). Major VC (HR: 2.31 [95% CI: 1.20 to 4.43], p = 0.012), and renal disease at baseline (HR: 2.26 [95% CI: 1.34 to 3.81], p = 0.002) were identified as independent predictors of 1-year mortality. CONCLUSIONS Major VC were frequent after TF-TAVR in the PARTNER trial using first-generation devices and were associated with high mortality. However, the incidence and impact of major VC on 1-year mortality decreased with lower-risk populations.

Clinical ResearchInterventional CardiologyVascular Complications After Transcatheter Aortic Valve Replacement: Insights From the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial

OBJECTIVES This study sought to identify incidence, predictors, and impact of vascular complications (VC) after transfemoral (TF) transcatheter aortic valve replacement (TAVR). BACKGROUND VC after TF-TAVR are frequent and may be associated with unfavorable prognosis. METHODS From the randomized controlled PARTNER (Placement of AoRTic TraNscathetER Valve) trial, a total of 419 patients (177 from cohort B [inoperable] and 242 from cohort A [operable high-risk]) were randomly assigned to TF-TAVR and actually received the designated treatment. First-generation Edwards-Sapien valves and delivery systems were used, via a 22- or 24-F sheath. The 30-day rates of major and minor VC (modified Valve Academic Research Consortium definitions), predictors, and effect on 1-year mortality were assessed. RESULTS Sixty-four patients (15.3%) had major VC and 50 patients (11.9%) had minor VC within 30 days of the procedure. Among patients with major VC, vascular dissection (62.8%), perforation (31.3%), and access-site hematoma (22.9%) were the most frequent modes of presentation. Major VC, but not minor VC, were associated with significantly higher 30-day rates of major bleeding, transfusions, and renal failure requiring dialysis, and with a significantly higher rate of 30-day and 1-year mortality. The only identifiable independent predictor of major VC was female gender (hazard ratio [HR]: 2.31 [95% confidence interval (CI): 1.08 to 4.98], p = 0.03). Major VC (HR: 2.31 [95% CI: 1.20 to 4.43], p = 0.012), and renal disease at baseline (HR: 2.26 [95% CI: 1.34 to 3.81], p = 0.002) were identified as independent predictors of 1-year mortality. CONCLUSIONS Major VC were frequent after TF-TAVR in the PARTNER trial using first-generation devices and were associated with high mortality. However, the incidence and impact of major VC on 1-year mortality decreased with lower-risk populations.

Percutaneous coronary intervention for cardiogenic shock in the SHOCK trial

OBJECTIVES We examined the clinical, angiographic, and procedural characteristics determining survival after percutaneous coronary intervention (PCI) for cardiogenic shock. BACKGROUND The SHOCK (SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK?) trial prospectively enrolled patients with shock complicating acute myocardial infarction (MI). Patients were randomized to a strategy of early revascularization or initial medical stabilization. METHODS Patients randomized to early revascularization underwent PCI or bypass surgery on the basis of predefined clinical criteria. Patients randomized to early revascularization who underwent PCI and had angiographic films available for analysis are the subject of this report (n = 82). RESULTS The median time from MI to PCI was 11 h. The majority of patients had occluded culprit arteries (Thrombolysis In Myocardial Infarction [TIMI] grade 0 or 1 flow in 62%) and multivessel disease (81%). One-year mortality in PCI patients was 50%. Mortality was 39% if PCI was successful but 85% if unsuccessful (p < 0.001). Mortality was 38% if TIMI flow grade 3 was achieved, 55% with TIMI grade 2 flow, and 100% with TIMI grade 0 or 1 flow (p < 0.001). Mortality was 67% if severe mitral regurgitation was documented. Independent correlates of mortality were as follows: increasing age (p < 0.001), lower systolic blood pressure (p = 0.009), increasing time from randomization to PCI (p = 0.019), lower post-PCI TIMI flow (0/1 vs. 2/3) (p < 0.001), and multivessel PCI (p = 0.040). CONCLUSIONS Restoration of coronary blood flow is a major predictor of survival in cardiogenic shock. Benefit appears to extend beyond the generally accepted 12-h post-infarction window. Surgery should be considered in shock patients with severe mitral insufficiency or multivessel disease not amenable to relatively complete percutaneous revascularization.

Angiographic findings and clinical correlates in Patients with cardiogenic shock complicating acute myocardial infarction : A report from the SHOCK Trial Registry

OBJECTIVES We sought to delineate the angiographic findings, clinical correlates and in-hospital outcomes in patients with cardiogenic shock (CS) complicating acute myocardial infarction. BACKGROUND Patients with CS complicating acute myocardial infarction carry a grave prognosis. Detailed angiographic findings in a large, prospectively identified cohort of patients with CS are currently lacking. METHODS We compared the clinical characteristics, angiographic findings, and in-hospital outcomes of 717 patients selected to undergo angiography and 442 not selected, overall and by shock etiology: left or right ventricular failure versus mechanical complications. RESULTS Patients who underwent angiography had lower baseline risk and a better hemodynamic profile than those who did not. Overall, 15.5% of the patients had significant left main lesions on angiography, and 53.4% had three-vessel disease, with higher rates of both for those with ventricular failure, compared with patients who had mechanical complications. Among patients who underwent angiography, those with ventricular failure had significantly lower in-hospital mortality than patients with mechanical complications (45.2% vs. 57.0%; p = 0.021). Importantly, for patients with ventricular failure, in-hospital mortality also correlated with disease severity: 35.0% for no or single-vessel disease versus 50.8% for three-vessel disease. Furthermore, mortality was associated with the culprit lesion location (78.6% in left main lesion, 69.7% in saphenous vein graft lesions, 42.4% in circumflex lesions, 42.3% in left anterior descending lesions, and 37.4% in right coronary artery lesions), and Thrombolysis In Myocardial Infarction (TIMI) flow grade (46.5% in TIMI 0/1, 49.4% in TIMI 2 and 26% in TIMI 3). CONCLUSIONS Patients who underwent angiographic study in the SHOCK Trial Registry had a more benign cardiac risk profile, more favorable hemodynamic findings and lower in-hospital mortality than those for whom angiograms were not obtained. Patients with CS caused by ventricular failure had more severe atherosclerosis, and a different distribution of culprit vessel involvement but lower in-hospital mortality, than those with mechanical complications. Overall in-hospital survival correlates with the extent of coronary artery obstructions, location of culprit lesion and baseline coronary TIMI flow grade.

Effect of ST segment measurement point on performance of standard and heart rate-adjusted ST segment criteria for the identification of coronary artery disease.

BackgroundRecent reports critical of the performance of heart rate-adjusted indexes of ST depression during exercise electrocardiography have used J-point rather than ST segment measurements. However, no standard exists for the optimal time after the J-point at which to measure ST segment deviation. Methods and ResultsTo assess the effect of ST segment measurement position on performance of standard exercise electrocardiographic criteria, the AST segment/heart rate (AST/HR) index, and the ST segment/heart rate (ST/HR) slope for the detection of coronary artery disease, the exercise electrocardiograms of 50 clinically normal subjects and 80 patients with known or likely coronary disease were analyzed using ST depression measured at both the J-point and at 60 msec after the J-point (J+60). A positive exercise electrocardiogram by standard criteria, defined as 0.1 mV or more of additional horizontal or downsloping ST depression at end exercise, had a specificity of 96% when ST depression was measured at either the J-point or J+60. There was no difference in sensitivity of standard electrocardiographic criteria at J+60 and J point (both 59%, p=NS). However, at matched specificity of 96%, the AST/HR index and ST/HR slope calculated using ST depression at J+60 were significantly more sensitive (90% and 93%) than when calculated using J-point depression (64% and 61%, each p < 0.001). Comparison of areas under respective receiver operating characteristic curves confirmed the superior performance of J+60 as opposed to J-point measurements for both the AST/HR index (0.98 versus 0.89,p=0.006) and the ST/HR slope (0.96 versus 0.87,p=O0.007) and also demonstrated modestly improved overall test performance for standard electrocardiographic criteria using J+60 measurements (0.88 versus 0.82, p = 0.001). ConclusionsUse of J-point measurements significantly degrades performance of heart rate-adjusted indexes of ST depression but has less effect on standard criteria. (Circulation 1991;84:57–66)

Comparison of Trends and Outcomes of Carotid Artery Stenting and Endarterectomy in the United States, 2001 to 2010

Background—Given the controversy regarding whether carotid endarterectomy (CEA) or carotid artery stenting (CAS) may be superior for stroke prevention, it is uncertain how recent clinical evidence, guidelines, and reimbursement policies have influenced the volume and outcomes after these procedures. Methods and Results—We conducted a serial, cross-sectional study with time trends of patients undergoing CAS (n=124 265) and CEA (n=1 260 647) between 2001 and 2010 from the Nationwide Inpatient Sample database. During the 10-year period, the frequency of CEA declined, whereas CAS use slowly increased. After multivariate propensity score–matched analysis, CAS was associated with an increased risk of death (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.40–2.04), stroke (OR, 1.43; 95% CI, 1.23–1.66), and major adverse events including death, stroke, and myocardial infarction (OR, 1.25; 95% CI, 1.13–1.39). In asymptomatic patients, there was no significant difference in major adverse events (OR, 1.08; 95% CI, 0.92–1.20; P=0.16 [P <0.001 for interaction between procedure type and symptom status]) between CAS and CEA. Importantly, there was a significant improvement in CAS outcomes during the course of 10 years (reduction in death [OR, 0.51; 95% CI, 0.49–0.67; P for trend=0.03] and major adverse events [OR, 0.75; 95% CI, 0.66–0.84; P for trend=0.05] comparing years 2010 versus 2001). Conclusions—In US hospitals between 2001 and 2010, CAS was associated with worse in-hospital outcomes, partly attributable to selection and ascertainment bias. Asymptomatic patients undergoing CAS versus CEA had similar adjusted rates of major adverse events. CAS outcomes improved significantly during the course of the decade likely attributable to improvements in patient selection, operator skills, and technological advancements.

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.

Calcified Amorphous Tumor of the Heart

A 44-year–old previously healthy man presented with progressive shortness of breath on exertion. Chest x-ray showed clear lung fields, but dense calcification was noted within the cardiac silhouette. Sixty-four–detector row cardiac computed tomographic angiography revealed diffuse calcific infiltration of the left ventricular (LV) myocardium, which also involved the papillary muscles and mitral chordal apparatus (Figure 1 and online-only Data Supplement Movie I). Calcific infiltration was most notable in the apical, lateral, and septal free walls. The right ventricle was spared except for contiguous …

Pheochromocytoma of the heart

This is a presentation of a unique case of cardiac pheochromocytoma during pregnancy. The case is significant because pheochromocytoma is a difficult diagnosis and its rarity during pregnancy may lead to this important diagnosis being overlooked, even though treatment is specific and highly successful.