An Integrated Imaging and Circulating Biomarker Approach for Secondary Tricuspid Regurgitation.

Secondary tricuspid regurgitation (sTR) is frequent among patients with heart failure with reduced ejection fraction (HFrEF), however it confers considerable diagnostic challenges. The assessment of neurohumoral activation may constitute a valuable supplement to the current imaging-based diagnostic process. This study sought to investigate the expression of complementary biomarkers in sTR and to evaluate the effectiveness of integrating their assessment into the diagnostic process. We enrolled 576 HFrEF patients recording echocardiographic and biochemical measurements, i.e., N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin, C-terminal pro-endothelin-1 (CT-pro-ET1), and copeptin. Plasma levels of the aforementioned neurohormones were significantly elevated with increasing sTR severity (p < 0.001 for all). CT-pro-ET1 and MR-proANP were the closest related to severe sTR (adj. OR 1.46; 95%CI 1.11-1.91, p = 0.006 and adj. OR 1.45, 95%CI 1.13-1.87, p = 0.004, respectively). In patients with moderate-to-severe sTR, adding selected biomarkers (i.e., CT-pro-ET1 and MR-proANP) resulted in a substantial improvement in the discriminatory power regarding long-term mortality (C-statistic: 0.54 vs. 0.65, p < 0.001; continuous NRI 57%, p < 0.001). Circulating biomarkers closely relate to sTR severity and correlate with hemodynamic and morphologic mechanisms of sTR. Specifically, MR-proANP and CT-pro-ET1 are closely linked to the presence of severe sTR, and a combined assessment with the guideline recommended echocardiographic grading significantly improves individual risk stratification.

Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic Stenosis.

BACKGROUND: The aim of this study was to examine the association between abnormal morphology of the proximal aorta and aortic stenosis (AS) progression rate. The main hypothesis was that morphologic changes of the proximal aorta, such as effacement of the sinotubular junction (STJ), result in increased biomechanical stresses and contribute to calcification and progression of AS. METHODS: Between 2010 and 2012, 426 patients with mild to moderate AS were included in this study. Proximal aortic dimensions were measured at three different levels (i.e., sinus of Valsalva, STJ, and ascending aorta), and sinuses of Valsalva/STJ and ascending aorta/STJ ratios were used to determine degree of aortic deformity. AS progression rate was assessed by annualized increase in mean gradient (median follow-up time, 3.1 years; interquartile range, 2.6-3.9 years). The degree of aortic flow turbulence was examined in 18 matched patients with and without STJ effacement using cardiac magnetic resonance phase-contrast imaging. RESULTS: Patients' mean age was 71 ± 13 years, and 64% were men. Patients with low ratios had greater AS progression (P < .05). After comprehensive adjustment, sinuses of Valsalva/STJ (P = .025) and ascending aorta/STJ (P = .027) ratios were independently associated with greater AS progression rate. Compared with patients without STJ effacement, those with effacement of the STJ had higher degrees of aortic flow turbulence (24.4% vs 17.2%, P = .038). CONCLUSIONS: Effacement of the STJ is independently associated with greater AS progression, regardless of arterial hemodynamics, aortic valve phenotype, or baseline AS severity. Patients with abnormal proximal aortic geometry had disturbed aortic flow patterns. These findings suggest an interrelation between proximal aorta morphology and stenosis progression.

Effect of growth hormone treatment on diastolic function in patients who have developed growth hormone deficiency after definitive treatment of acromegaly.

OBJECTIVE: Although growth hormone (GH) replacement is prescribed for patients with hypopituitarism due to many etiologies, it is not routinely prescribed for patients with GH deficiency (GHD) after cure of acromegaly (acroGHD). This study was designed to investigate the effect of GH replacement on cardiac parameters in acroGHD. DESIGN: We prospectively evaluated for 12months 23 patients with acroGHD: 15 subjects on GH replacement and eight subjects not on GH replacement. Main outcome measures included LV mass corrected for body surface area (LVM/BSA) and measures of diastolic dysfunction (E/A ratio and deceleration time), as assessed by echocardiography. RESULTS: After 12months of follow-up, there were no differences between the GH-treated group and the untreated group in LVM/BSA (GH: 74.4±22.5g/m(2) vs untreated: 72.9±21.3g/m(2), p=0.89), E/A ratio (GH: 1.21±0.39 vs untreated: 1.08±0.39, p=0.50) or deceleration time (GH: 224.5±60.1ms vs untreated: 260±79.8ms, p=0.32). The overall degree of diastolic function was similar between the groups with 42.9% of untreated subjects and 50% of GH-treated subjects (p=0.76) classified as having normal diastolic function at follow-up. CONCLUSIONS: There were no significant differences in LVM/BSA or parameters of diastolic function in patients with a history of acromegaly treated for GHD as compared to those who were untreated. These data are reassuring with respect to cardiovascular safety with GH use after treatment for acromegaly, although further longer term study is necessary to evaluate the safety and efficacy of GH treatment in this population.

Progression of atrial remodeling in patients with high-burden atrial fibrillation: Implications for early ablative intervention.

BACKGROUND: Advanced atrial remodeling predicts poor clinical outcomes in human atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to define the magnitude and predictors of change in left atrial (LA) structural remodeling over 12 months of AF. METHODS: Thirty-eight patients with paroxysmal AF managed medically (group 1), 20 undergoing AF ablation (group 2), and 25 control patients with no AF history (group 3) prospectively underwent echocardiographic assessment of strain variables of LA reservoir function at baseline and at 4, 8, and 12 months. In addition, P-wave duration (Pmax,, Pmean) and dispersion (Pdis) were measured. AF burden was quantified by implanted recorders. Twenty patients undergoing ablation underwent electroanatomic mapping (mean 333 ± 40 points) for correlation with LA strain. RESULT: Group 1 demonstrated significant deterioration in total LA strain (26.3% ± 1.2% to 21.7% ± 1.2%, P < .05) and increases in Pmax (132 ± 3 ms to 138 ± 3 ms, P < .05) and Pdis (37 ± 2 ms to 42 ± 2 ms, P < .05). AF burden ≥10% was specifically associated with decline in strain and with P-wave prolongation. Conversely, group 2 manifest improvement in total LA strain (21.3% ± 1.7% to 28.6% ± 1.7%, P <.05) and reductions in Pmax (136 ± 4 ms to 119 ± 4 ms, P < .05) and Pdis (47 ± 3 ms to 32 ± 3 ms, P < .05). Change was not significant in group 3. LA mean voltage (r = 0.71, P = .0005), percent low voltage electrograms (r = -0.59, P = .006), percent complex electrograms (r = -0.68, P = .0009), and LA activation time (r = -0.69, P = .001) correlated with total strain as a measure of LA reservoir function. CONCLUSION: High-burden AF is associated with progressive LA structural remodeling. In contrast, AF ablation results in significant reverse remodeling. These data may have implications for timing of ablative intervention.

Mitral valve and papillary muscle abnormalities in hypertrophic obstructive cardiomyopathy.

PURPOSE OF REVIEW: This section reviews abnormalities of the mitral valve apparatus that are associated with hypertrophic obstructive cardiomyopathy. RECENT FINDINGS: Mitral valve abnormalities in hypertrophic obstructive cardiomyopathy include leaflet elongation and thickening and hypertrophy with anterior displacement of the papillary muscles. This combination contributes to the development of systolic anterior motion. The resultant flow forces during systolic anterior motion pulling the leaflets into the left ventricular outflow tract also result in reduced leaflet coaptation and a posteriorly directed mitral regurgitant jet. Additional mitral valve abnormalities include degenerative leaflet changes, aberrant chordal attachments and papillary muscle anomalies. SUMMARY: Mitral valve abnormalities are common in hypertrophic obstructive cardiomyopathy and play an important role in the pathophysiology of dynamic left ventricular outflow tract obstruction.

Amiodarone-induced destructive thyroiditis associated with coronary artery vasospasm and recurrent ventricular fibrillation.

A 55-year-old male on long-term amiodarone therapy presented with ischaemic chest pain and recurrent unwitnessed syncope. Interrogation of his internal cardiac defibrillator, which had been inserted 4 years earlier, revealed two episodes of ventricular fibrillation, the timing of which corresponded to his syncopal events. Severe spontaneous coronary artery vasospasm was observed on coronary angiogram. Thyroid function testing revealed severe hyperthyroidism with a diagnosis of type 2 amiodarone-induced thyrotoxicosis (AIT) subsequently made. Treatment with prednisolone therapy was commenced and thyroid function rapidly normalized. Prednisolone was weaned without recurrence of hyperthyroidism and on last review, 6 months after initial presentation, he remains free from further chest pain and arrhythmias. Our patient's presentation is a very rare case of AIT-associated coronary artery spasm and documented ischaemic ventricular fibrillation with fortunate survival.

Left ventricular ejection fraction and absence of ACE inhibitor/angiotensin II receptor blocker predicts appropriate defibrillator therapy in the primary prevention population.

INTRODUCTION: Implantable cardioverter defibrillators (ICD) significantly reduce mortality in patients with left ventricular (LV) dysfunction. However, little is known of the predictors of appropriate device activation in the primary prevention population. The aim of the present study was to determine predictors of appropriate device therapy in patients receiving ICDs for primary prevention. METHODS & RESULTS: One hundred twenty-six patients with a left ventricular ejection fraction (LVEF) of < 35% and no prior documented ventricular arrhythmias underwent ICD implantation. The ICD implanted was single chamber in 60 (48%), dual chamber in 10 (8%), and biventricular in 56 (44%) patients and programmed with a single ventricular fibrillation (VF) zone at >180 beats per minute. Mean age was 58 +/- 13 years and mean LVEF was 23 +/- 7%. Fifty-two percent had ischemic cardiomyopathy and 66% were New York Heart Association heart failure class II/III. During a mean follow-up period of 589 +/- 353 days, 17 (13%) patients received appropriate device therapy and three (4%) received inappropriate shocks. Appropriate ICD therapy was associated with reduced LVEF (mean 19.9% vs 23.7%, P = 0.02) and the patients were less likely to have received angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (AIIRB) (65% vs 90%, P = 0.04). Multivariate analysis revealed lack of ACEI/AIIRB (odds ratio [OR]= 0.06, 95% confidence interval [CI]= 0.01-0.37, P = <0.01) and lower LVEF (OR = 0.88, 95% CI 0.79-0.98, P = 0.02) predicted appropriate device activation. There was no difference in transplant-free survival between the appropriate therapy and no/inappropriate therapy groups, LVEF <20% and LVEF >20% group, and lack of ACEI/AIIRB and ACEI/AIIRB group. CONCLUSION: Appropriate device activation occurred in 13% of patients in a primary prevention population. LVEF and absence of ACEI/AIIRB predicted appropriate ICD therapy.