Pericardial complications and postcardiac injury syndrome after cardiovascular implantable electronic device placement : A meta-analysis and systematic review.

BACKGROUND: Postcardiac injury syndrome (PCIS) is an emerging condition including pericarditis with or without pericardial effusion after an injury to cardiac tissue. Data are lacking on its incidence and clinical predictors after cardiovascular implantable electronic device (CIED) placement. We therefore performed this meta-analysis to determine the incidence of PCIS. METHODS: Medline, Embase, and Cochrane CENTRAL databases were searched according to PRISMA guidelines from February 2007 to February 2017 for studies evaluating pericardial complications subsequent to CIED implantation. Primary outcome was the total number of cases of pericarditis, pericardial effusion, and cardiac tamponade documented. RESULTS: Of 2931 references, 22 articles (enrolling 188,944 patients) were included. Pooled estimates from random-effects analysis showed an overall incidence of 5.82 per 1000 patients (95% confidence interval [CI], 4.33-8.17) at 30 days, and 1.60 per 1000 (95% CI: 0.13-3.07) at 1 year. Advanced age and prior coronary artery bypass graft (CABG) surgery were associated with increased rates of pericardial complications. CONCLUSION: Our analysis revealed that CIED implantations are associated with a low incidence (0.6%) of pericardial complications at 30 days. Patients with advanced age and prior CABG are high-risk patients for pericardial complications.

Impact of ischemia and scar on therapeutic benefit of myocardial revascularization.

The question of how to optimally manage coronary artery disease (CAD) has been a challenge for the cardiology community. The results of early, large randomized clinical trials (RCTs) comparing strategies of medical therapy alone versus revascularization plus medical therapy in patients with stable CAD suggested a survival advantage for a revascularization strategy in the setting of more advanced, higher-risk CAD (left main, three-vessel CAD), but a superiority of medical therapy in patients with more limited, relatively lower-risk CAD (one vessel, limited two-vessel CAD). The results of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials redefined the management of CAD, supporting the concept that the impact of aggressively applied modern "medical therapy" on patient survival and patient-reported outcomes is not further improved by the addition of percutaneous intervention. On the other hand, RCTs incorporating fractional flow reserve have shown that this physiologic metric can help identify which patients will benefit from a revascularization strategy. This paradigm has been extended to the use of myocardial perfusion imaging-identified ischemia to determine which patients may have enhanced survival with early revascularization versus medical therapy. Although data from a series of observational studies suggest that inducible ischemia on myocardial perfusion scintigraphy can identify revascularization candidates, several studies, including substudies from major RCTs, do not support this idea. Until RCTs comparing revascularization with medical therapy strategies are performed, many questions remain open. The correct thresholds for treatment, the metric to guide treatment, and how revascularization should be performed are as yet undefined.

SPECT/PET myocardial perfusion imaging versus coronary CT angiography in patients with known or suspected CAD.

Stress SPECT myocardial perfusion imaging (MPI) is the most commonly utilized stress imaging technique for patients with suspected or known coronary artery disease (CAD) and has a robust evidence base including the support of numerous clinical guidelines. Gated SPECT is a well-established noninvasive imaging modalities that is a core element in evaluation of patients with both acute and stable chest pain syndromes. Over the past decade, PET has become increasingly used for the same applications. By comparison, cardiac computed tomography (CT) is a more recently developed method, providing non-invasive approaches for imaging coronary atherosclerosis and coronary artery stenosis. Non-contrast CT for imaging the extent of coronary artery calcification (CAC), in clinical use since the mid-1990's, has a very extensive evidence base supporting its use in CAD prevention. While contrast-enhanced CT for noninvasive CT coronary angiography (CCTA) is relatively new, it has already developed an extensive base of evidence regarding diagnosing obstructive CAD and more recently evidence has emerged regarding its prognostic value. It is likely that non-contrast CT or CCTA for assessment of extent of atherosclerosis will become an increasing part of mainstream cardiovascular imaging practices as a first line test. In some patients, further ischemia testing with MPI will be required. Similarly, MPI will continue to be widely used as a first-line test, and in some patients, further anatomic definition of atherosclerosis with CT will also be appropriate. This review will provide a synopsis of the available literature on imaging that integrates both CT and MPI in strategies for the assessment of asymptomatic patients for their atherosclerotic coronary disease burden and risk as well as symptomatic patients for diagnosis and guiding management. We propose possible strategies through which imaging might be used to identify asymptomatic candidates for more intensive prevention and risk factor modification strategies as well as symptomatic patients who would benefit from referral to invasive coronary angiography for consideration of revascularization.

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction.

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.

Evidence-based risk assessment in noninvasive imaging.

UNLABELLED: Assessment of important clinical and economic outcomes has become central to the evaluation of patient care. Outcome research is deeply rooted in epidemiology, including the use of multivariable, risk-adjusted regression analysis. In our current health care environment, these methods are increasingly being used to assess the quality of care and to profile physicians and laboratories. Nuclear medicine physicians therefore need to better understand outcome methodologies in order to evaluate patient outcomes, develop guidelines, and decide on patient management. METHODS: This review describes the methods of assessing the diagnostic and prognostic value of nuclear medicine techniques and, briefly, the methodologic limitations of sample size, frequency and type of events, and follow-up periods and the incremental value of imaging. Also described are logistic regression and Cox proportional hazards modeling. Models for risk assessment are designed to identify whether patients require conservative (i.e., low-risk) or aggressive (i.e., high-risk) treatment. Treatment selection is currently based on risk assessment and the formation of an integrated, empiric risk stratification algorithm of care. This review also includes the methods of assessing economic effectiveness and quality-of-life issues for patients examined with nuclear medicine techniques. CONCLUSION: In this era of constrained resources, low-cost outpatient-based care may be of increasing importance. High-quality evidence of the clinical and economic outcome of nuclear imaging is essential for helping health care providers and payers assess its value.

Risk assessment of patients with known or suspected CAD using stress myocardial perfusion SPECT. Part II: Determining cost-effective test strategies.

In this era of cost containment, each step of a testing protocol must be evaluated carefully for appropriateness and prognostic value. Exercise stress single-photon emission CT (SPECT) is finding a niche in the examination of patients with known or suspected coronary artery disease. When preceded by careful patient screening, stress SPECT, alone or combined with other testing, may prove to be a tool that is both cost-effective and clinically effective.

Acute myocardial infarction following recovery from a normal treadmill exercise test.

Cardiologists today rely on stress testing to provide valuable diagnostic information about their patients. How and why can it cross the line to become a trigger for acute coronary events? Is patient selection important to avoid complications? Follow this patient through his stress test.

Diagnostic strategies for women with suspected coronary artery disease.

The clinician evaluating a woman with symptoms potentially indicative of coronary heart disease faces the challenge of choosing the appropriate diagnostic test. The use of noninvasive testing in women has been controversial due to a perception of diminished accuracy, limited female representation, and technical limitations that compromise efficacy. Recent meta-analyses and large observational series report marked improvements in accuracy for women undergoing exercise treadmill, echocardiography, and nuclear testing. Electron beam computed tomography is a relatively new technique, and the body of evidence is still developing. An adequate body of evidence supports the use of noninvasive testing for intermediate risk, symptomatic women and may result in improved diagnostic and therapeutic decision making.

Transmyocardial laser revascularization with excimer laser: clinical results at 1 year.

BACKGROUND: Transmyocardial laser revascularization, a new strategy for the treatment of diffuse ischemic heart disease, uses laser technology for the theoretical purpose of forming transmyocardial channels in the heart to increase perfusion to ischemic zones. This report summarizes our initial clinical experience with the procedure. METHODS: Excimer transmyocardial laser revascularization was performed in a reversibly ischemic region of the heart in 15 patients. Ischemia and myocardial viability were evaluated by assessment of symptoms and of results of radionuclide single photon emission computed tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring. RESULTS: No adverse events occurred as a result of the laser revascularization, although 1 patient with preoperative ventricular arrhythmias died 48 hours postoperatively as a result of refractory ventricular tachycardia. Angina class decreased significantly from base line values in patients who had undergone the procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months, 1.8+/-0.8 at 12 months; p<0.002), and nitroglycerin requirements were similarly decreased in patients who had undergone laser revascularization (mean g/wk of sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3 months, 4+/-2 at 6 months, 2+/-1 at 12 months; p<0.02). Exercise tolerance testing demonstrated increase in exercise duration compared with base line values (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3 months, and 9.0+/-3.9 at 12 months; p>0.05); those increases were not large enough to be statistically significant, however. CONCLUSIONS: Our data are consistent with the concept that excimer transmyocardial laser revascularization in individuals with significant ischemic heart disease appears to be well tolerated, can be performed safely, and may lead to a reduction in ischemic symptomatology.

Clinical and economic outcomes assessment in nuclear cardiology.

The future of nuclear medicine procedures, as understood within our current economic climate, depends upon its ability to provide relevant clinical information at similar or lower comparative costs. With an ever-increasing emphasis on cost containment, outcome assessment forms the basis of preserving the quality of patient care. Today, outcomes assessment encompasses a wide array of subjects including clinical, economic, and humanistic (i.e., quality of life) outcomes. For nuclear cardiology, evidence-based medicine would require a threshold level of evidence in order to justify the added cost of any test in a patient's work-up. This evidence would include large multicenter, observational series as well as randomized trial data in sufficiently large and diverse patient populations. The new movement in evidence-based medicine is also being applied to the introduction of new technologies, in particular when comparative modalities exist. In the past 5 years, we have seen a dramatic shift in the quality of outcomes data published in nuclear cardiology. This includes the use of statistically rigorous risk-adjusted techniques as well as large populations (i.e., > 500 patients) representing multiple diverse medical care settings. This has been the direct result of the development of multiple outcomes databases that have now amassed thousands of patients worth of data. One of the benefits of examining outcomes in large patient datasets is the ability to assess individual endpoints (e.g., cardiac death) as compared with smaller datasets that often assess combined endpoints (e.g., death, myocardial infarction, or unstable angina). New technologies for the diagnosis of coronary artery disease have contributed to the rising costs of care. In the United States and in Europe, costs of care have risen dramatically, consuming an ever-increasing amount of available resources. The overuse of diagnostic angiography often leads to unnecessary revascularization that does not lead to improvement in outcome. Thus, the potential exists that stress SPECT imaging, a highly effective diagnostic tool, could effect substantial change in reducing inappropriate use of an invasive procedure resulting in cost effective cardiac care. A synthesis of current economic evidence in gated SPECT imaging will be presented. In conclusion, a current state of the evidence review is presented on the clinical and economic data using nuclear cardiology imaging.

Sustained reduction of exercise perfusion defect extent and severity with isosorbide mononitrate (Imdur) as demonstrated by means of technetium 99m sestamibi.

BACKGROUND: The impact of long-acting nitrates on the extent and severity of stress-induced myocardial ischemia is not well described, especially after long-term treatment. METHODS: Forty patients with chronic stable angina and reversible ischemia on an exercise stress myocardial perfusion single photon emission computed tomography (ex-SPECT) were prospectively studied in a 6-week period. At baseline, rest thallium-201/exercise stress technetium 99m sestamibi SPECT was performed, followed by treatment with extended-release isosorbide 5-mononitrate (5-ISMN, Imdur). Follow-up ex-SPECT was performed 5 days and 6 weeks after the initiation of therapy with extended-release 5-ISMN. The exercise treadmill testing (ETT) protocol and exercise duration of the follow-up studies were the same as that of the baseline ETT. Defect extent and severity were analyzed both by means of an automated quantitative method, with CEqual software, and visually, with a 20-segment scoring system (which was also used to derive a summed stress score [SSS]). RESULTS: In the 6-week study period, significant reductions occurred in both the extent and the severity of exercise-induced ischemia by means of quantitative SPECT (13.8% [P<.0003] and 12.7% [P<.0003], respectively). There was no significant change in these variables between stages 2 (day 5) and 3 (6 weeks), indicating no development of tolerance to the nitrate effect. Similar reductions were noted by means of the visual analysis (SSS reduction of 13.0% [P<.002]) in the entire study period. CONCLUSIONS: Patients with chronic-stable-angina treated with a long-acting nitrate demonstrate improvement in myocardial perfusion defect extent and severity in an extended period by means of both visual and quantitative analysis of sequential exercise testing to the same rate-pressure product end point.

Noninvasive strategies for the estimation of cardiac risk in stable chest pain patients. The Economics of Noninvasive Diagnosis (END) Study Group.

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.

Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121.

BACKGROUND: Adenovirus (Ad) vector-mediated gene therapy strategies have emerged as promising modalities for the "biological revascularization" of tissues. We hypothesized that direct intramyocardial, as opposed to intracoronary, administration of an Ad vector coding for the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) would provide highly focal Ad genome levels, and increases in VEGF, ideal for inducing localized therapeutic angiogenesis. METHODS: Persistence and regional distribution of the vector were assessed by TaqMan real-time quantitative polymerase chain reaction technology and enzyme-linked immunosorbent assay, after intramyocardial Ad(GV)VEGF121.10 in the rat, and either intramyocardial or intracoronary (circumflex territory) vector in Yorkshire swine. Based on these results, we assessed the focal nature of the improved cardiac blood flow in a previously reported porcine myocardial ischemia model. RESULTS: Intramyocardial delivery of Ad(GV)VEGF121.10 in the rat resulted in local persistence of the Ad genome that decreased 1,000-fold over 3 weeks, with peak myocardial VEGF expression 24 to 72 h after vector delivery. After intramyocardial Ad(GV)VEGF121.10 in the circumflex distribution of pigs, Ad vector genome and VEGF protein levels were more than 1,000-fold and more than 90-fold higher, respectively, in this distribution than in other myocardial regions. In comparison, intracoronary injection yielded maximum myocardial Ad genome and VEGF levels 33-fold and 9-fold lower, respectively, than that after intramyocardial delivery. Angiograms obtained 28 days after intramyocardial Ad(GV)VEGF121.10 demonstrated rapid circumflex reconstitution via collaterals localized to the region of vector administration. CONCLUSIONS: These studies demonstrate that direct intramyocardial administration of Ad(GV)VEGF121.10 results in focal genome and VEGF levels, including focal angiogenesis, sufficient to normalize blood flow to the ischemic myocardium, findings that are relevant to designing human trials of gene therapy-mediated cardiac angiogenesis.