Laboratory parameters of cardiac and kidney dysfunction in cardio-renal syndromes.

"Cardio-Renal Syndromes" (CRS) are disorders of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pathophysiology of CRS is complex, and there is accumulating evidence that various novel biomarkers are useful for diagnosis, prognostication, and risk stratification in patients with heart failure and chronic kidney disease (CRS). When both the heart failure (HF) and CKD occur together, it is important to have biomarkers that are able to risk stratify patients by looking at both their heart and kidney aspects. There are some promising newer renal biomarkers that may contribute to a better evaluation and prediction of prognosis in CRS patients. Most of the renal biomarkers studies in CRS have been performed in the setting of cardiac surgery, acute coronary syndrome (ACS), HF or after exposure to radiocontrast media in diagnostic and/or therapeutic percutaneous coronary procedures. Natriuretic peptides (NPs) have been validated as an important cardiac biomarker for risk stratification and prognostication in HF patients with or without CKD. However, the best cutoff values for each stage of CKD, including those on renal replacement therapy, are yet to be ascertained. In this context, it is likely that panels of multiple biomarkers will be needed for optimal evaluation, risk stratification, timely treatment initiation, and follow-up of patients with CRS.

The association of patent foramen ovale morphology and stroke size in patients with paradoxical embolism.

BACKGROUND: Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke through paradoxical embolization to the cerebral circulation. This study evaluated the relationship between the morphological and functional size of the PFO by echocardiography compared with cerebral infarct volume identified on MRI. METHODS AND RESULTS: Patients who were referred to interventional cardiology with the diagnosis of cryptogenic stroke were included and had either a transesophageal echocardiogram or an intracardiac echo and a brain MRI at the time of stroke. Transesophageal echocardiogram or intracardiac echo was used to obtain PFO measurements. MRI of the brain with 3 sequences (T2, diffusion-weighted imaging, and fluid-attenuated inversion recovery) was used to diagnose acute stroke and measure the infarct volume. In the 72 patients studied, the median measured stroke volume was 4.3 cm(3) on diffusion-weighted imaging, 4.1 cm(3) on T2, and 3.5 cm(3) on fluid-attenuated inversion recovery. There was no significant correlation between the PFO height, length, septum secundum thickness, or echo bubble grade and the infarct volume measured from the 3 MRI sequences. There was a significant correlation between septal excursion distance and infarct volume (r=0.35; P=0.005), but the 12 patients with atrial septal aneurysm did not have the largest strokes. CONCLUSIONS: This analysis revealed that septal excursion distance correlates with stroke size by MRI. However, smaller PFO size without the presence of atrial septal aneurysm may still be associated with significant strokes. There was no significant association between PFO height, length by echo, or shunt grade by transcranial Doppler study and brain infarct volume. Therefore, PFO size or morphology should not be the only criteria to decide whether a PFO should be closed.

Biomarkers of cardiac and kidney dysfunction in cardiorenal syndromes.

The role of biomarkers is rapidly emerging as an important tool in the management of the cardiorenal syndromes (CRS). Natriuretic peptides (NPs), due to their low cost and rapid and accurate ability to provide additional information not surmised from clinical evaluation, are the standard bearer for the newer biomarkers. Although the NP-guided therapy has been shown to improve patient outcomes, this has yet to be demonstrated for the novel renal biomarkers. Most of the renal biomarkers studies in CRS have been performed in the setting of cardiac surgery. It will be critical to validate these new biomarkers in multicenter and prospective studies encompassing a broad spectrum of patients. Work with NPs has also shown that novel biomakers are not to be used as 'stand-alone' tests; rather they are best used as adjuncts to everything else the health care provider brings to the table. It is likely that panels of multiple biomarkers will be needed for optimal evaluation, risk stratification, timely treatment initiation and follow-up of patients with CRS.

Use of biomarkers in evaluation of patients with heart failure.

Despite advances in the understanding of the pathophysiology of heart failure, its diagnosis and management still remain challenging. Biomarkers have added significant value to the clinical evaluation of heart failure. While their use is not intended as a substitute for clinical judgment, their relevance in diagnosis, management, and prognosis has been proven. This review focuses on biomarkers resulting from hemodynamic stress, injury and inflammation, and their clinical relevance in modern practice.

Prevalence of migraine headaches in patients with congenital heart disease.

The prevalence of migraine headaches (MH) is 12% in the general population and increases to 40% in patients with patent foramen ovale. This study evaluated the prevalence of MH in patients with congenital heart disease (CHD). Of 466 patients contacted from the UCLA Adult Congenital Heart Disease Center, 395 (85%) completed a questionnaire to determine the prevalence of MH. Patients were stratified by diagnosis of right-to-left, left-to-right, or no shunt. A group of 252 sex-matched patients with acquired cardiovascular disease served as controls. The prevalence of MH was 45% in adults with CHD compared to 11% in the controls (p<0.001). Of the 179 patients with MH, 143 (80%) had migraines with aura and 36 (20%) had migraines without aura versus 36% and 64% observed in the controls (p<0.001). The frequency of MH was 52% in the right-to-left shunt group, 44% in the left-to-right, and 38% in the no shunt group (p=NS). In patients with a right-to-left shunt who underwent surgical repair, 47% had complete resolution of MH, whereas 76% experienced >50% reduction in headache days per month. In conclusion, the prevalence of MH in all groups of adults with CHD is 3 to 4 times more than a sex-matched control population, with increasing prevalence of MH in patients with no shunt, left-to-right, and right-to-left shunt. The higher than expected frequency of MH in patients with CHD without an intracardiac shunt, suggests additional mechanisms to explain the significant association with MH.

Five-year experience with percutaneous closure of patent foramen ovale.

Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke, arterial desaturation, decompression illness, and migraine headache (MH). This study evaluated the safety of percutaneous transcatheter PFO closure in patients with cryptogenic stroke, transient ischemic attack, or arterial desaturation. Additionally, symptomatic reduction in MH was determined after interatrial shunt closure. Of the 252 patients referred to the University of California, Los Angeles, with PFO, 131 underwent closure of the interatrial communication with a CardioSEAL (n = 30) or Amplatzer (n = 101) device. PFO morphology was evaluated with transesophageal echocardiography. Follow-up was conducted at 1 to 2 months with echocardiography, with clinical assessment annually thereafter. At an average follow-up of 30 months, there was no recurrence of any thromboembolic event (transient ischemic attack, stroke, or peripheral). There was a reduction in MH, defined as the complete resolution of headache or a >50% reduction in the number of headache days, in 85% of patients after PFO closure. Temporary problems after device implantation, including chest discomfort and palpitations, were reported in 23% of patients and occurred more frequently in patients with nickel hypersensitivity (p <0.05). In conclusion, transcatheter PFO closure is an effective and safe therapeutic modality in the prevention of thromboembolic events and MH associated with interatrial shunting in patients who present with cryptogenic stroke. Pending randomized, controlled trials are necessary to determine if this invasive approach is preferable to medical therapy for the prevention of recurrent stroke or as primary treatment for patients with MH.

Assessment of intermediate severity coronary lesions in the catheterization laboratory.

The management of intermediate coronary lesions, defined by a diameter stenosis of 40% to 70%, continues to be a therapeutic dilemma for cardiologists. The 2-dimensional representation of the arterial lesion provided by angiography is limited in distinguishing intermediate lesions that require stenting from those that simply need appropriate medical therapy. In the era of drug-eluting stents, some might propose that stenting all intermediate coronary lesions is an appropriate solution. However, the possibility of procedural complications such as coronary dissection, no reflow phenomenon, in-stent restenosis, and stent thrombosis requires accurate stratification of patients with intermediate coronary lesions to appropriate therapy. Intravascular ultrasound (IVUS) and fractional flow reserve index (FFR) provide anatomic and functional information that can be used in the catheterization laboratory to designate patients to the most appropriate therapy. The purpose of this review is to discuss the critical information obtained from IVUS and FFR in guiding treatment of patients with intermediate coronary lesions. In addition, the importance of IVUS and FFR in the management of patients with serial stenosis, bifurcation lesions, left main disease, saphenous vein graft disease, and acute coronary syndrome will be discussed.

Drug-eluting stents: preventing restenosis.

The introduction of percutaneous transluminal coronary angioplasty has revolutionized the field of cardiology by providing patients with coronary artery disease immediate and effective therapy. Overshadowing the early success of angioplasty was the high rate of angiographic restenosis and recurrent symptoms at 6 months. The use of stents reduced the incidence of restenosis; however, the rise in the number of patients undergoing percutaneous interventions produced a new problem of restenosis occurring within the stent: in-stent restenosis (ISR). Mechanical approaches, including directional and rotational atherectomy and systemic pharmacotherapy, have failed to demonstrate a reduction in ISR in randomized clinical trials. Intravascular brachytherapy is currently the only approved therapy for ISR, although this treatment has numerous unresolved questions and is not effective in a large percent of patients. Drug-eluting stents have reduced the incidence of restenosis by providing localized therapy to the targeted lesion without systemic toxicity. The purpose of this review is to synthesize data from major clinical trials involving the 2 most successful agents used in the prevention of restenosis: sirolimus and paclitaxel. The cellular and molecular mechanisms of both ISR and restenosis postangioplasty derived from animal models will be introduced. Second, an overview of 3 alternate interventions that attempt to reduce the rates of restenosis is presented. Finally, the major randomized, controlled trials involving sirolimus and paclitaxel are described, and their clinical implications and use as a possible solution in the prevention of restenosis is discussed.