Aaron M. From

Effects of vasodilation in heart failure with preserved or reduced ejection fraction implications of distinct pathophysiologies on response to therapy.

OBJECTIVES The purpose of this study was to compare hemodynamic responses to vasodilator therapy in patients with heart failure (HF) and preserved ejection fraction (HFpEF) versus HF and reduced ejection fraction (HFrEF). BACKGROUND There is no proven therapy for HFpEF. In the absence of data, medicines with established benefit in HFrEF such as vasodilators are frequently prescribed for HFpEF. METHODS We compared baseline hemodynamics and acute responses to vasodilation with intravenous sodium nitroprusside in patients with HFrEF (n = 174) and HFpEF (n = 83), determined invasively by cardiac catheterization. RESULTS Baseline blood pressure, stroke volume, and cardiac output were greater in HFpEF than HFrEF, while pulmonary artery mean and pulmonary wedge pressures were similar. Left ventricular filling pressures were reduced to a similar extent in each group with nitroprusside, but the drop in systemic arterial pressure was 2.6-fold greater in HFpEF (p < 0.0001), and improvements in stroke volume and cardiac output were each ∼60% lower in HFpEF compared to HFrEF (p < 0.0001). Despite similarly elevated filling pressures, HFpEF patients were fourfold more likely than HFrEF to experience a reduction in stroke volume with nitroprusside (p < 0.0001), suggesting greater vulnerability to preload reduction. Pulmonary artery systolic pressure dropped more in HFpEF than in HFrEF despite similar reduction in pulmonary mean pressure and resistance, suggesting higher right ventricular systolic elastance in HFpEF. CONCLUSIONS As compared to patients with HFrEF, patients with HFpEF experience greater blood pressure reduction, less enhancement in cardiac output, and greater likelihood of stroke volume drop with vasodilators. These findings emphasize fundamental differences in the 2 HF phenotypes and suggest that more pathophysiologically targeted therapies are needed for HFpEF.

Mortality Associated With Nephropathy After Radiographic Contrast Exposure

OBJECTIVE To define outcomes from contrast-induced nephropathy (CIN) after both intra-arterial and intravenous administration of contrast medium. PATIENTS AND METHODS We performed a retrospective case-matched cohort study at Mayo Clinics site in Rochester, MN, from April 1, 2004, to March 31, 2006. All contrast procedures were evaluated for inclusion. Contrast-induced nephropathy was defined as creatinine elevation of 25% or more after contrast exposure or of more than 0.5 mg/dL within 7 days of contrast exposure. Cases of CIN were matched 1:3 with controls by age, sex, pre-procedure creatinine elevation, diabetes mellitus, and type of imaging procedure. RESULTS A total of 809 patients who developed CIN were matched to 2427 patients who did not develop CIN after contrast exposure. In multivariate analyses, CIN was significantly associated with 30-day mortality (odds ratio, 3.37; 95% confidence interval [CI], 2.58-4.41; P<.001) and overall mortality (hazard ratio, 1.57; 95% CI, 1.32-1.86; P<.001) after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. Intravenous contrast administration was a risk factor for 30-day mortality (odds ratio, 2.91; 95% CI, 1.17-7.23; P=.02) and overall mortality (hazard ratio, 3.02; 95% CI, 1.89-4.82; P<.001) compared with intra-arterial administration of contrast after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. CONCLUSION Contrast-induced nephropathy after administration of contrast medium is associated with increased mortality. This risk is higher in patients in whom contrast medium is administered intravenously than in those in whom it is administered intra-arterially.

Sodium bicarbonate is associated with an increased incidence of contrast nephropathy: a retrospective cohort study of 7977 patients at mayo clinic.

BACKGROUND AND OBJECTIVES The role of sodium bicarbonate in preventing contrast nephropathy needs to be evaluated in clinical settings. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective cohort study at Mayo Clinic in Rochester, Minnesota, to assess the risk of contrast nephropathy associated with the use of sodium bicarbonate, N-acetylcysteine, and the combination of sodium bicarbonate with N-acetylcysteine from April 2004 to May 2005. Contrast nephropathy was defined as postexposure creatinine elevation of > or =25% or >0.5 mg/dl within 7 d of contrast exposure. RESULTS A total of 11,516 contrast exposures in 7977 patients had creatinine values available for review before and after contrast exposure. More than 90% of exposures to agents prophylactic for contrast nephropathy were available for analysis. Sodium bicarbonate was used in 268 cases, N-acetylcysteine was used in 616 cases, and both agents were used in combination in 221 cases of contrast exposure. After adjustment for total volume of hydration, medications, age, gender, prior creatinine, contrast iodine load, prior exposure to contrast material, type of imaging study, heart failure, hypertension, renal failure, multiple myeloma, and diabetes mellitus, use of sodium bicarbonate alone was associated with an increased risk of contrast nephropathy compared with no treatment (odds ratio 3.10, 95% confidence interval 2.28 to 4.18; P < 0.001). N-acetylcysteine alone and in combination with sodium bicarbonate was not associated with any significant difference in the incidence of contrast nephropathy. CONCLUSIONS The use of intravenous sodium bicarbonate was associated with increased incidence of contrast nephropathy. Use of sodium bicarbonate to prevent contrast nephropathy should be evaluated further rather than adopted into clinical practice.

Current Status of Endomyocardial Biopsy

Endomyocardial biopsy (EMB) is widely used for surveillance of cardiac allograft rejection and for the diagnosis of unexplained ventricular dysfunction. Typically, EMB is performed through the jugular or femoral veins and is associated with a serious acute complication rate of less than 1% using current flexible bioptomes. Although it is accepted that EMB should be used to monitor for rejection after transplant, use of EMB for the diagnosis of various myocardial diseases is controversial. Diagnosis of myocardial disease in the nontransplant recipient is often successful via noninvasive investigations including laboratory evaluation; echocardiography, nuclear studies, and magnetic resonance imaging can yield specific diagnoses in the absence of invasive EMB. Therefore, use of the technique is patient specific and depends on the potential prognostic and treatment information gained by establishing a pathologic diagnosis beyond noninvasive testing.

Iodixanol Versus Low-Osmolar Contrast Media for Prevention of Contrast Induced Nephropathy Meta-analysis of Randomized, Controlled Trials

Background—Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. Methods and Results—We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (P=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Conclusions—Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.

Temporal Trends and Improved Outcomes of Percutaneous Coronary Revascularization in Nonagenarians

OBJECTIVES The aim of this study was to describe the clinical characteristics and the outcomes of patients 90 years of age or older who were treated with percutaneous coronary intervention (PCI). BACKGROUND There is a paucity of outcomes data among nonagenarians undergoing PCI. METHODS We evaluated the outcomes of all patients 90 years of age or older in the Mayo Clinic PCI registry and examined trends over time. RESULTS Over a period of 19 years, we identified 138 nonagenarians (66% women; age 92.2 +/- 2.0 years). Mean duration of hospitalization was 3.7 +/- 3.1 days, and the median follow-up duration was 3.6 years. Ninety-one percent of patients presented with an acute coronary syndrome and underwent urgent or emergent revascularization. Technical success rate was 91%. Overall, the frequency of in-hospital death, Q-wave myocardial infarction, and major adverse cardiac events (composite of death, Q-wave myocardial infarction, urgent or emergent coronary artery bypass grafting, and cerebrovascular accident) were 9.4%, 0.7%, and 12.3%, respectively. The long-term survival of the cohort was not significantly different than that of an age, gender, and calendar year of birth-matched Minnesota cohort. The cohort was divided into 2 groups according to the time of their intervention: pre-2000 (n = 32) and 2000 to 2006 (n = 106). The in-hospital mortality decreased markedly: 22% to 6% (p = 0.006), respectively. CONCLUSIONS Our study demonstrates that, in carefully selected patients, PCI in contemporary practice may be performed with high technical success with relatively low mortality and morbidity. Thus, advanced age alone must not be considered a contraindication to performing coronary angiography and PCI when clear indications are present.

Sheathless transradial intervention using standard guide catheters

Our aim was to report our preliminary experience performing complex transradial interventions using a sheathless technique with standard large bore nonhydrophilic guiding catheters.

Iodixanol Versus Low-Osmolar Contrast Media for Prevention of Contrast Induced Nephropathy

Background—Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. Methods and Results—We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (P=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Conclusions—Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.

Heart Failure with Preserved Ejection Fraction: Pathophysiology and Emerging Therapies

Approximately half of patients with heart failure (HF) have a preserved ejection fraction (HFpEF). Morbidity and mortality are similar to HF with reduced EF (HFrEF), yet therapies with unequivocal benefit in HFrEF have not been shown to be effective in HFpEF. Recent studies have shown that the pathophysiology of HFpEF, initially believed to be due principally to diastolic dysfunction, is more complex. Appreciation of this complexity has shed new light into how HFpEF patients might respond to traditional HF treatments, while also suggesting new applications for novel therapies and strategies. In this review, we shall briefly review the pathophysiologic mechanisms in HFpEF, currently available clinical trial data, and finally explore new investigational therapies that are being developed and tested in ongoing and forthcoming trials.

Characteristics and outcomes of patients with abnormal stress echocardiograms and angiographically mild coronary artery disease (<50% stenoses) or normal coronary arteries.

BACKGROUND Abnormal cardiac stress imaging findings are not always associated with angiographically significant coronary artery disease. The outcomes of patients with such false-positive findings have not been extensively examined. The aim of this retrospective study was to describe the characteristics and outcomes of patients with abnormal stress echocardiographic findings who had false-positive results compared with those who had true-positive results. METHODS Of 1,477 consecutive patients (mean age, 66 +/- 12 years; 61% men) with abnormal stress echocardiographic findings who underwent coronary arteriography within 30 days, death from any cause was ascertained. RESULTS At coronary arteriography, 997 patients (67.5%) had true-positive results, defined by the presence of angiographically significant coronary artery disease (> or = 50% stenoses), and 480 (32.5%) had false-positive results, defined by <50% stenoses or normal coronary arteries. Of the subgroup of patients with markedly abnormal stress echocardiographic findings (n = 605), 28% had <50% stenoses or normal coronary arteries. During an average follow-up period of 2.4 +/- 1.0 years, there were 140 deaths. The adjusted likelihood of subsequent death for patients with <50% stenoses compared to patients with > or = 50% stenoses after abnormal stress echocardiography was 1.05 (95% confidence interval, 0.86-1.31; P = .62). CONCLUSIONS A sizable proportion of patients with abnormal stress echocardiographic results who are referred for coronary angiography have false-positive findings. The outcomes of patients with false-positive results were similar to those of patients with true-positive results. This finding suggests that patients with false-positive results on stress echocardiography should still receive intensive risk factor management and careful clinical follow-up.