Unipolar voltage mapping criteria for right ventricular septum: Influence of the aortic root.

INTRODUCTION: Unipolar voltage mapping through its wider "field of view" can identify substrate deeper to the endocardium on the right ventricular (RV) free wall and left ventricle. The reference value(s) for normal endocardial (ENDO) unipolar voltage (UNI) for the septal aspect of the right ventricle (RV) and the effect of the aortic root that is directly opposed to the posterior septal plane of the RV outflow tract (RVOT) have not been established. METHODS AND RESULTS: We performed detailed (185 ± 70, range 127-342 points) RV ENDO UNI maps in 9 patients without structural heart disease; 6 had magnetic resonance (MR) imaging; 5 were males; the mean age was 49 ± 11 years. For MR analysis, the location of the aortic root was defined and its effect on unipolar voltage determined. The UNI voltage on posterior RVOT was lower (mean 6.56 ± 2.33 mV, 95% CI 6.08-7.05), compared to the rest of the septal aspect of RV (mean 8.33 ± 2.34 mV, P < 0.001, 95% CI 7.84-8.84). MR analysis confirmed that the lowest voltage region was opposite to MR-defined aortic root. Using a cutoff for UNI abnormality of 6.0 mV for the posterior aspect of the RVOT opposite to the aortic root and 7.5 mV for the rest of the septal aspect of the RV, there was no confluent area of unipolar abnormality in any patient. CONCLUSION: We defined normal ENDO UNI cutoffs as 7.5 mV for the septal aspect of the RV with adjustment to 6.0 mV over the posterior RVOT opposite to the aortic root.

Recovery of renal dysfunction after catheter ablation of outflow tract ventricular arrhythmias in patients with ventricular premature depolarization-mediated cardiomyopathy.

PURPOSE: Frequent ventricular premature depolarizations (VPDs) may cause cardiomyopathy (VPDCM), which often improves after VPD suppression. This study aimed to evaluate whether ablation of outflow tract ventricular arrhythmias (OT VAs) in patients with VPDCM improves renal in addition to left ventricular (LV) function. METHODS: We retrospectively evaluated 153 patients with OT VAs and examined VPD burden and LV ejection fraction (LVEF), as well as estimated glomerular filtration rate (eGFR) pre- and post-ablation. LV dysfunction was defined as LVEF <50 % and impaired renal function was defined as eGFR of <60 mL/min/1.73m2. RESULTS: Fifty-five patients had VPDCM. During mean follow-up of 14 months, 140 (92 %) were free from arrhythmia. In patients with VPDCM, patients with baseline LVEF 40-50 % had greater improvement in the post-ablation LVEF compared to patients with baseline LVEF <40 % (p < 0.01). At baseline, 36 (72 %) patients had renal dysfunction, 29 (81 %) of whom had improvement in eGFR from baseline after successful ablation from eGFR 51 to 57 mL/min/1.73m2. There was a significant association between cardiac (ΔLVEF ≥10 %) and renal (ΔeGFR ≥10 %) improvement (r = 0.54, p = 0.04). Using logistic regression analysis, procedural success was an independent predictor of improvement of cardiac (odds ratio [OR] = 13.7, p = 0.03) and renal function (OR = 21.0, p = 0.047). CONCLUSIONS: Successful catheter ablation of OT VA reduces VPD burden and is associated with improved cardiac and renal function in patients with VPDCM.

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target.

BACKGROUND: The relationship between heart failure (HF) and the serotonergic system has been established in animal studies. However, data on human plasma serotonin level in HF and its significance over the course of the disease is lacking. METHODS: Serotonin levels were measured in 173 patients (108 males, 65 females), 116 were stable HF and 40 were acute decompensated HF patients. The normal control group included 17 healthy volunteers with no known medical or psychiatric conditions. Patients receiving medications affecting serotonin receptors and those with pulmonary hypertension were excluded. All patients, except for those in the decompensated group, were on stable doses of HF medications. RESULTS: Plasma serotonin levels were significantly elevated in decompensated HF patients compared with stable patients (P=0.002). Higher plasma serotonin levels were associated with worse HF symptoms (NYHA class) and the presence of systolic dysfunction, and was borderline associated with low peak oxygen consumption during cardiopulmonary exercise testing (P=0.055). These results were independent of age, gender, race, hypertension, diabetes, renal failure, weight, coronary artery disease (CAD), atrial fibrillation and medication use. CONCLUSIONS: Serotonin is a marker for decompensation in patients with chronic heart failure. Higher serotonin levels were associated with worse HF symptoms and systolic dysfunction.

Thrombocytopaenia as a Prognostic Indicator in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Studies suggest that thrombocytopaenia is associated with a higher mortality in several diseases. Little is known about the effect of low platelet count on mortality in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to determine the prognostic value of thrombocytopaenia in these patients by assessing all-cause mortality. METHODS: A total of 1,907 patients with HFrEF, defined by left ventricular ejection fraction <40% on echocardiography, were analysed in this multi-centre retrospective study. All patients were on medical therapy with a beta-blocker and an angiotensin-converting enzyme inhibitor. Patients were categorised into two groups based on platelet count measured within one month of the diagnosis of HFrEF: normal to mild thrombocytopaenia (platelet count 100,000-450,000 per uL); and moderate to severe thrombocytopaenia (platelet count <100,000 per uL). One-year all-cause mortality was compared between the two groups. RESULTS: Mean age was 65±15 years and 62% of patients were male. Overall one-year mortality was 17.2% with higher mortality among patients with HFrEF and moderate/severe thrombocytopaenia compared to those with normal/mild thrombocytopaenia (33.0% vs. 15.4%, p <0.001). After adjusting for baseline characteristics, patients with HFrEF and moderate/severe thrombocytopaenia had a higher mortality compared to patients with normal/mild thrombocytopaenia (HR 1.84, 95% CI 1.33-2.56, p <0.001). CONCLUSION: In patients with HFrEF, higher degree of thrombocytopaenia is associated with higher all-cause mortality. These findings may support the use of platelet counts as a prognostic marker in the assessment of the patient with HFrEF.

Non-invasive assessment of low risk acute chest pain in the emergency department: A comparative meta-analysis of prospective studies.

BACKGROUND: The aim of this meta-analysis was to compare the diagnostic accuracy of cardiac computed tomographic angiography (CCTA), stress echocardiography (SE) and radionuclide single photon emission computed tomography (SPECT) for the assessment of chest pain in emergency department (ED) setting. METHODS: A systematic review of Medline, Cochrane and Embase was undertaken for prospective clinical studies assessing the diagnostic efficacy of CCTA, SE or SPECT, as compared to intracoronary angiography (ICA) or the later presence of major adverse clinical outcomes (MACE), in patients presenting to the ED with chest pain. Standard approach and bivariate analysis were performed. RESULTS: Thirty-seven studies (15 CCTA, 9 SE, 13 SPECT) comprising a total of 7800 patients fulfilled inclusion criteria. The respective weighted mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and total diagnostic accuracy for CCTA were: 95%, 99%, 84%, 100% and 99%, for SE were: 84%, 94%, 73%, 96% and 96%, and for SPECT were: 85%, 86%, 57%, 95% and 88%. There was no significant difference between modalities in terms of NPV. Bivariate analysis revealed that CCTA had statistically greater sensitivity, specificity, PPV and overall diagnostic accuracy when compared to SE and SPECT. CONCLUSIONS: All three modalities, when employed by an experienced clinician, are highly accurate. Each has its own strengths and limitations making each well suited for different patient groups. CCTA has higher accuracy than SE and SPECT, but it has many drawbacks, most importantly its lack of physiologic data.

Outcomes in World Health Organization group II pulmonary hypertension: mortality and readmission trends with systolic and preserved ejection fraction-induced pulmonary hypertension.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has been increasingly recognized as a leading cause of pulmonary hypertension (HFpEF-PH). It remains unknown how HFpEF-PH fares in relation to systolic HF (reduced ejection fraction)-induced PH (HFrEF-PH). Therefore, we sought to determine the long-term morbidity and mortality of HFpEF-PH and HFrEF-PH. METHODS AND RESULTS: We studied all patients over a 6-year period with symptomatic HF and severe PH (PASP ≥65 mm Hg) in The Bronx, New York. We classified patients as having either preserved (≥50%) or reduced (≤35%) left ventricular ejection fraction. Trends in mortality and HF readmission rates were defined in 650 patients (HFrEF-PH: n = 277; HFpEF-PH: n = 373). HFpEF-PH patients were older and more often female and white. HFrEF-PH patients were more often black, had ischemic cardiomyopathy, and were on typical HF drug regimens. Patients with HFpEF-PH had a significantly increased all-cause 5-year mortality (52% vs 42%; P = .024). HFpEF-PH was a significant predictor of mortality (adjusted hazard ratio 1.70; P = .012). Patients with HFrEF-PH had more HF readmissions (≥1) than patients with HFpEF-PH (28.6% vs 15%; P = .003), especially within the 1st year (9.1% vs 1.7%; P = .005). CONCLUSIONS: Patients with HFrEF-PH and HFpEF-PH have a significantly elevated long-term mortality, with HFpEF-PH having a higher 5-year mortality rate. These findings testify to the overall poor prognosis of World Health Organization Group II PH, especially HFpEF-PH.

Coronary computed tomography angiography for the detection of cardiac allograft vasculopathy: a meta-analysis of prospective trials.

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of coronary computed tomography angiography (CCTA) for detecting cardiac allograft vasculopathy (CAV) in comparison with conventional coronary angiography (CCAG) alone or with intravascular ultrasound (IVUS). BACKGROUND: CAV limits long-term survival after heart transplantation, and screening for CAV is performed on annual basis. CCTA is currently not recommended for CAV screening due to the limited accuracy reported by early studies. Technological advances, however, might have resulted in improved test performance and might justify re-evaluation of this recommendation. METHODS: A systematic review of Medline, Cochrane, and Embase for all prospective trials assessing CAV using CCTA was performed using a standard approach for meta-analysis for diagnostic test and a bivariate analysis. RESULTS: Thirteen studies evaluating 615 patients (mean age 52 years, 83% male) and 9,481 segments fulfilled inclusion criteria. Patient-based analyses comparing CCTA versus CCAG for the detection of any CAV (> luminal irregularities) and significant CAV (stenosis ≥50%), showed mean weighted sensitivities of 97% and 94%, specificities of 81% and 92%, a negative predictive value (NPV) of 97% and 99%, a positive predictive value (PPV) of 78% and 67%, and diagnostic accuracies of 88% and 94%, respectively. There was a strong trend toward improved sensitivity (97% vs. 91%, p = 0.06) and NPV (99% vs. 97%, p = 0.06) to detect significant CAV with 64-slice compared with 16-slice CCTA. A patient-based analysis of 64-slice CCTA versus IVUS showed a mean weighted sensitivity and specificity of 81% and 75% to detect CAV (intimal thickening >0.5 mm), whereas the PPV and NPV were 93% and 50%, respectively. CONCLUSIONS: CCTA using currently available technology is a reliable noninvasive imaging alternative to coronary angiography with an excellent sensitivity, specificity, and NPV for the detection of CAV.

Effect of race on left ventricular ejection fraction decline after initial improvement with beta blockers in patients with non-ischemic cardiomyopathy: a retrospective analysis.

BACKGROUND: Although beta blockers (BBs) are established therapy in heart failure, some patients whose left ventricular ejection fraction (LVEF) initially increases on BB therapy experience a subsequent LVEF decline. This study aimed to evaluate the proportion of patients with non-ischemic cardiomyopathy (NICM) whose LVEF declines while on BB therapy and determine important predictors of LVEF decline. METHODS: A retrospective analysis of 238 patients receiving a BB (carvedilol, metoprolol succinate, or tartrate), with an ejection fraction of ≤40% and NICM, whose LVEF initially rose ≥5% after 1 year of BB therapy, was conducted. Post-response LVEF decline ≥5% to a final LVEF of ≤35% was evaluated within 4 years of BB initiation. RESULTS: In our study, we had 52 Caucasians (22%), 78 Hispanics (33%), and 108 African Americans (45%). Overall, 32 patients (13.44 %) had post-response LVEF decline. The nadir LVEF of patients with post-response LVEF decline was 25% (interquartile range 20-27). Compared with others, Hispanics had lower nadir LVEF (22%, p < 0.001). Important predictors of LVEF decline were Hispanic race (odds ratio (OR) 6.094, p < 0.001), New York Heart Association (NYHA) class (OR 2.287, p < 0.05), baseline LVEF (OR 1.075, p < 0.05), and age (OR 0.933, p < 0.001). CONCLUSION: A significant proportion (13.44%) of NICM patients with LVEF increase over 1 year of BB therapy experienced subsequent LVEF decline. Race, NYHA class, baseline LVEF, and age are important predictors of this decline.

Effects of ß-adrenergic blockade on left ventricular remodeling among Hispanics and African Americans with chronic heart failure.

BACKGROUND: Although ß-blockers (BBs) have been shown to improve cardiac function, there is individual and ethnic variation in BB clinical response. We examined the effects of BBs on left ventricular remodeling among African Americans (AAs), Hispanics, and Caucasians with systolic heart failure. HYPOTHESIS: There is ethnic variability in the effects of BBs on cardiac remodeling. METHODS: There were 185 AAs, 159 Hispanics, and 74 Caucasians selected with ejection fraction ≤ 40% from any etiology. Change in left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVEDD), and degree of mitral regurgitation (MR) in response to 1 year of BBs was evaluated retrospectively. RESULTS: Overall, there was a significant improvement in LVEF, LVEDD, and degree of MR in AAs and Caucasians after 1 year of BBs (P < 0.001 vs baseline). Compared with other races, Hispanics (%) had no significant improvement in LVEDD and degree of MR, and had fewer patients with reverse remodeling: LVEF (42.77%), LVEDD (5.03%), and MR (16.35%). In multivariable analysis, Hispanic and AA race were important predictors of LVEF and LVEDD (P < 0.01) but not MR response. CONCLUSIONS: Although most patients demonstrated improvement of LVEF, there seems to be ethnic variability in the effects of BBs on cardiac remodeling. Degree of MR and LVEDD failed to show improvement among Hispanics.

CMR imaging for the evaluation of myocardial stunning after acute myocardial infarction: a meta-analysis of prospective trials.

BACKGROUND: Myocardial stunning is an important sequela of acute coronary syndromes and its determination might affect decisions on defibrillator implantation and assist devices after myocardial infarction (AMI). The aim of the study was to evaluate and compare the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of cardiac magnetic resonance imaging (CMR) assessing myocardial stunning after acute myocardial infarction using low-dose dobutamine (LDD), end-diastolic wall thickness, and contrast delayed enhancement (DE). METHODS AND RESULTS: A systematic review of Medline, Embase, and Cochrane for all prospective trials assessing myocardial stunning by CMR following AMI was performed using a standard approach for meta-analysis for diagnostic test and a bivariate analysis. Search results revealed 9384 studies, out of which 17 met criteria. A total of 634 patients (mean age 59 years, 85% male, mean left ventricular ejection fraction: 52%) were included. DE-CMR had a weighted sensitivity of 87% and specificity of 68% to detect myocardial stunning using 50% transmurality as a cut-off, with a PPV and NPV of 83 and 72%, respectively. With an overall diagnostic accuracy of 82%, LDD-CMR had a sensitivity of 67% and a specificity of 81%, with a PPV and NPV of 82 and 63%, respectively. LDD showed an overall accuracy of 74%. CONCLUSION: DE-CMR has a higher sensitivity, whereas LDD-CMR has a higher specificity for the detection of viable stunned myocardium following myocardial infarction. Whether the combination of DE and LDD may improve the prediction of myocardial recovery remains to be determined.

Detection of left atrial appendage thrombus by cardiac computed tomography in patients with atrial fibrillation: a meta-analysis.

BACKGROUND: Transesophageal echocardiogram (TEE) is considered the gold standard modality in detecting left atrial/LA appendage (LA/LAA) thrombi. However, this is a semi-invasive procedure with rare but potential life-threatening complications. Cardiac computed tomography has been proposed as an alternative method. The purpose of this meta-analysis was to evaluate the diagnostic accuracy of cardiac computed tomography assessing LA/LAA thrombi in comparison with TEE. METHODS AND RESULTS: A systematic review of Medline, Cochrane, and Embase to look for clinical trials assessing detection of LA/LAA thrombi by cardiac computed tomography when compared with TEE in patients with a history of atrial fibrillation before electric cardioversion/pulmonary vein isolation or after cardioembolic cerebrovascular accident was performed using standard approach and bivariate analysis. Nineteen studies with 2955 patients (men, 71%; mean age, 61±4 years) fulfilled the inclusion criteria. Most studies (85%, 16 studies) used 64-slide multidetector computed tomography and 15 studies (79%) were electrocardiographic-gated. The incidence of LA/LAA thrombi was 8.9% (SD, ±7). The mean sensitivity and specificity were 96% and 92%, whereas the positive predictive value and negative predictive value were 41% and 99%, respectively. The diagnostic accuracy was 94%. In a subanalysis of studies in which delayed imaging was performed, the diagnostic accuracy significantly improved to a mean weighted sensitivity and specificity of 100% and 99%, respectively, whereas the positive predictive value and negative predictive value increased to 92% and 100%, respectively. The accuracy for this technique was 99%. CONCLUSIONS: Cardiac computed tomography, particularly when delayed imaging is performed, is a reliable alternative to TEE for the detection of LA/LAA thrombi/clot, avoiding the discomfort and risks associated with TEE.

The effect of nesiritide on renal function and other clinical parameters in patients with decompensated heart failure and preserved ejection fraction.

The role of nesiritide in patients with decompensated heart failure with preserved ejection fraction (dHFpEF) has not been previously studied. In this investigation, the authors retrospectively analyzed the effect of nesiritide on renal function and clinical outcomes in patients admitted with dHFpEF. Of the 658 patients included, 328 were treated with nesiritide while 330 patients were treated with standard diuretic therapy. In both the nesiritide and no nesiritide groups, there was a significant change in mean glomerular filtration rate (GFR) and creatinine at 72 hours as well as at day of discharge (P<.001). This trend did not progress at 1 month in the nesiritide group, although it did in the no nesiritide group. At 1 month after therapy, however, there was a significant difference between the two groups in the mean change of GFR and creatinine (P<.001). There was no significant difference in >25% decrease of GFR anytime through day 30 (25% vs 29.69%, P=.236) between the two groups. On multivariate analysis, nesiritide was an important predictor of renal function at 1 month (P<.05). Thus, nesiritide can be administered safely without negatively impacting long-term renal function in patients admitted with dHFpEF.

Effect of nesiritide in isolated right ventricular failure secondary to pulmonary hypertension.

Treatment of right ventricular failure (RVF) can be challenging due to the correlation between RVF and worsening renal function with diuretic therapy. Nesiritide has been studied in patients with left ventricular failure but has not been evaluated in isolated RVF. The authors retrospectively analyzed 140 patients admitted with RVF, pulmonary hypertension (PH), and preserved left ventricular systolic function. Seventy patients were treated with nesiritide while the remaining patients received only furosemide (no nesiritide group). Serum creatinine and GFR at baseline, 72 hours, discharge, and 1 month post-treatment, as well as hemodynamic data were compared between the groups. In the nesiritide group, there was a significant decrease in mean GFR (42.77±25.33, P<.001) at day of discharge and 1 month post-nesiritide infusion (41.17±24.94, P<.001) but not in the no nesiritide group. There was a significant difference in >25% decrease in GFR anytime through day 30 (47.14% vs. 25.71%, P=.036) between the two groups. On multivariate analysis, nesiritide remained an important predictor of renal function at discharge and at 1 month (P<.01) as well as a predictor of >25% decrease in GFR anytime through day 30 (P=.007). Thus, nesiritide is associated with worsening kidney function in patients with RVF in the setting of PH.

Use of cardiac radionuclide imaging to identify patients at risk for arrhythmic sudden cardiac death.

Sudden cardiac death (SCD) accounts for about ½ of all cardiovascular deaths, in most cases the result of a lethal ventricular arrhythmia. Patients considered at risk are often treated with an implantable cardiac defibrillator (ICD), but current criteria for device use, based largely on left ventricular ejection fraction (LVEF), leads to many patients receiving ICDs that they do not use, and many others not receiving ICDs but who suffer SCD. Thus, better methods of identifying patients at risk for SCD are needed, and radionuclide imaging offers much potential. Recent work has focused on imaging of cardiac autonomic innervation. (123)I-mIBG, a norepinephrine analog, is the tracer most studied, and a variety of positron emission tomographic tracers are also under investigation. Radionuclide autonomic imaging may identify at-risk patients with ischemic coronary artery disease, particularly following myocardial infarction and in the setting of hibernating myocardium. Most studies have been done in the setting of congestive heart failure (CHF), with a recent large multicenter study of patients with advanced disease, typically at high risk of SCD, showing that (123)I-mIBG can identify a low risk subgroup with an extremely low incidence of lethal ventricular arrhythmias and cardiac death, therefore, perhaps not requiring an ICD. Cardiac neuronal imaging has been shown to be better predictive of lethal arrhythmias/cardiac death than LVEF and New York Heart Association class, as well as various ECG parameters. Autonomic imaging will likely play an important role in the advancement of cardiac molecular imaging.