Rajesh Janardhanan

Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial

BACKGROUND Diastolic dysfunction might represent an important pathophysiological intermediate between hypertension and heart failure. Our aim was to determine whether inhibitors of the renin-angiotensin-aldosterone system, which can reduce ventricular hypertrophy and myocardial fibrosis, can improve diastolic function to a greater extent than can other antihypertensive agents. METHODS Patients with hypertension and evidence of diastolic dysfunction were randomly assigned to receive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched placebo. Patients in both groups also received concomitant antihypertensive agents that did not inhibit the renin-angiotensin system to reach targets of under 135 mm Hg systolic blood pressure and under 80 mm Hg diastolic blood pressure. The primary endpoint was change in diastolic relaxation velocity between baseline and 38 weeks as determined by tissue doppler imaging. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170924. FINDINGS 186 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo. 43 patients were lost to follow-up or discontinued the assigned intervention. Over 38 weeks, there was a 12.8 (SD 17.2)/7.1 (9.9) mm Hg reduction in blood pressure in the valsartan group and a 9.7 (17.0)/5.5 (10.2) mm Hg reduction in the placebo group. The difference in blood pressure reduction between the two groups was not significant. Diastolic relaxation velocity increased by 0.60 (SD 1.4) cm/s from baseline in the valsartan group (p<0.0001) and 0.44 (1.4) cm/s from baseline in the placebo group (p<0.0001) by week 38. However, there was no significant difference in the change in diastolic relaxation velocity between the groups (p=0.29). INTERPRETATION Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used.

Usefulness of myocardial contrast echocardiography using low-power continuous imaging early after acute myocardial infarction to predict late functional left ventricular recovery.

Microvascular perfusion is a prerequisite for ensuring viability early after acute myocardial infarction (AMI). For adequate assessment of myocardial perfusion, both myocardial blood volume and velocity need to be evaluated. Due to its high frame rate, low-power continuous myocardial contrast echocardiography (MCE) can rapidly assess these parameters of myocardial perfusion. We hypothesized that the technique can accurately differentiate necrotic from viable myocardium after reperfusion therapy in AMI. Accordingly, 50 patients underwent low-power continuous MCE using intravenous Optison (Amersham Health, Amersham, Middlesex, United Kingdom) 7 to 10 days after AMI. Myocardial perfusion (contrast opacification assessed over 15 cardiac cycles after the destruction of microbubbles with high energy pulses) and wall thickening were assessed at baseline. Regional and global left ventricular (LV) function was reassessed after 12 weeks. Out of the 297 dysfunctional segments, MCE detected no contrast enhancement during 15 cardiac cycles in 172 segments, of which 160 (93%) failed to show improvement. MCE demonstrated contrast opacification during 15 cardiac cycles in 77 segments, of which 65 (84%) showed recovery of function. The greater the extent and intensity of contrast opacification, the better the LV function at 3 months (p <0.001, r = -0.91). Almost all patients (94%) with <20% perfusion in dysfunctional myocardium (assessing various cut-offs) failed to demonstrate an improvement in LV function. MCE and peak creatine kinase proved to be independent predictors of functional recovery (p <0.001). In conclusion, low-power continuous MCE is an accurate and rapid bedside technique to identify microvascular perfusion after AMI. This technique may be utilized to reliably predict late recovery of function in dysfunctional myocardium after AMI.

Elevated circulating fibrocyte levels in patients with hypertensive heart disease

Objective: Autopsy and biopsy studies have shown that there is significantly more fibrosis in hearts of patients with hypertensive heart disease compared to normal hearts. Fibrocytes, a population of circulating bone marrow-derived cells, have been shown to home to tissues and promote scar formation in several diseases, but their role in human hypertensive heart disease has not been investigated to date. Our objective was to determine whether fibrocyte levels are elevated in individuals with hypertensive heart disease. Methods: We measured peripheral blood fibrocyte levels and their activated phenotypes in 12 individuals with hypertensive heart disease as determined by increased left ventricular mass on noninvasive imaging and compared them to fibrocyte levels from 19 healthy normal controls and correlated them to cardiac MRI findings. Results: Compared to normal controls, individuals with hypertensive heart disease had significantly higher circulating levels of total fibrocytes [median (interquartile range); 149000 (62200–220000) vs. 564500 (321000–1.2900e+006), P < 0.0001, respectively] as well as activated fibrocytes [15700 (6380–19800) vs. 478500 (116500–1.2360e+006) P < 0.0001]. Moreover, the fibrocyte subsets expressing the chemokine markers CXCR4 (P < 0.0001), CCR2 (P < 0.0001), CCR7 (P < 0.0001) and coexpression of both CXCR4 and CCR2 (P < 0.0001) were significantly elevated in patients with hypertensive heart disease compared to controls. Lastly, in patients with hypertensive heart disease there was a strong correlation between left ventricular mass index and total fibrocytes (r = 0.65, P = 0.037) and activated fibrocytes (r = 0.70, P = 0.016). Conclusion: Our data suggest that bone marrow-derived circulating fibrocytes are associated with the presence and extent of left ventricular hypertrophy in patients with hypertensive heart disease.

Hypertension as a risk factor for heart failure.

Hypertension remains a significant risk factor for development of congestive heart failure CHF), with various mechanisms contributing to both systolic and diastolic dysfunction. The pathogenesis of myocardial changes includes structural remodeling, left ventricular hypertrophy, and fibrosis. Activation of the sympathetic nervous system and renin-angiotensin system is a key contributing factor of hypertension, and thus interventions that antagonize these systems promote regression of hypertrophy and heart failure. Control of blood pressure is of paramount importance in improving the prognosis of patients with heart failure.

Improved prediction of outcome by contrast echocardiography determined left ventricular remodelling parameters compared to unenhanced echocardiography in patients following acute myocardial infarction

AIMS Contrast echocardiography has been shown to be a more accurate method of assessing left ventricular (LV) remodelling compared with unenhanced echocardiography after acute myocardial infarction (AMI). However, whether this translated into improved prediction of outcome is not known. METHODS AND RESULTS Accordingly, a total of 89 consecutive patients undergoing contrast echocardiography and unenhanced echocardiography 7 to 10 days after AMI and reperfusion therapy were followed up for cardiac death (CD) and AMI. LV ejection fraction (LVEF), LV end-systolic volume (ESV), and LV end-diastolic volume were assessed by the two methods independently. Outcome data were obtained (mean 46 +/- 16 months).There were 15 (17%) events (eight CDs and seven AMIs). LVEF and ESV with contrast echocardiography were found to be independent multivariable predictors of CD (P = 0.04 and P = 0.02, respectively) and CD or AMI (P = 0.02 and P = 0.01, respectively). Furthermore, LVEF and ESV with contrast echocardiography provided incremental information for the prediction of CD (P = 0.004 and P = 0.004, respectively) and CD or AMI (P = 0.02 and P = 0.03, respectively). CONCLUSION Contrast echocardiography provided improved prediction of outcome compared with unenhanced echocardiography following AMI.

Role of Strain Imaging in Right Heart Disease: A Comprehensive Review

Advances in the imaging techniques of the heart have fueled the interest in understanding of right heart pathology. Recently, speckle tracking echocardiography has shown to aid in understanding various right heart diseases and better management. Its role is well established in diagnosing right heart failure, pulmonary artery hypertension, arrhythmogenic right ventricular dysplasia and congenital heart disease. We review the basic mechanics of speckle tracking and analyze its role in various right heart conditions.

Imaging in hypertensive heart disease.

Hypertensive heart disease is the target organ response to arterial hypertension. Left ventricular hypertrophy represents an important predictor for cardiovascular events. Myocardial fibrosis, a common end point in hypertensive heart disease, has been linked to the development of left ventricular hypertrophy and diastolic dysfunction. Echocardiography is clinically useful in the detection of left ventricular hypertrophy and the assessment of diastolic function. Although echocardiography is more widely available, cardiac magnetic resonance has been demonstrated to be more reproducible for the estimation of left ventricular mass. Future developments in cardiac magnetic resonance techniques may facilitate the quantification of diffuse fibrosis that occurs in hypertensive heart disease. Thus, advances in cardiac imaging provide comprehensive, noninvasive tools for imaging left ventricular hypertrophy, diastolic dysfunction, myocardial fibrosis and ischemia observed in hypertensive heart disease. The objective of this article is to summarize the state-of-the-art and the future of multimodality imaging of hypertensive heart disease.

Comparison Between Myocardial Contrast Echocardiography and 99mTechnetium Sestamibi Single Photon Emission Computed Tomography Determined Myocardial Viability in Predicting Hard Cardiac Events Following Acute Myocardial Infarction

The extent of residual myocardial viability (MV) after acute myocardial infarction (AMI) is an important determinant of the outcome. Single photon emission computed tomography (SPECT) is widely used to assess MV after an AMI. However, myocardial contrast echocardiography (MCE), a relatively new technique for the assessment of MV, has better spatial and temporal resolution than SPECT. The present study evaluated whether MV determined by MCE is comparable to that determined using SPECT for the prediction of hard cardiac events after an AMI. Accordingly, 99 patients who had undergone simultaneous rest low-power MCE and nitrate-enhanced SPECT 7 days after an AMI were followed up for cardiac death and AMIs. Both MCE perfusion (1 = normal; 2 = reduced; and 3 = absent) and SPECT tracer uptake (0 = normal; 1 = mildly reduced; 2 = moderately reduced; 3 = severely reduced; and 4 = absent) were scored on a 16-segment left ventricular model. The contrast perfusion index and SPECT perfusion index were calculated by adding the respective scores in the 16 segments and dividing by 16. The contrast perfusion index and SPECT perfusion index were used as a measure of the residual MV on MCE and SPECT, respectively. Of the 99 patients recruited, 95 were available for the follow-up examination (follow-up 46 +/- 16 months). A total of 15 events (16%) occurred (8 cardiac deaths and 7 AMIs). Of the clinical, biochemical, echocardiographic, and SPECT markers of prognosis, the only independent predictors of cardiac death and cardiac death or AMI were age and MV as determined by MCE (p = 0.01 and p = 0.002, respectively). In conclusion, MV determined by MCE at rest was superior to nitrate-enhanced SPECT for the prediction of hard cardiac events after AMI.

Mitral valve replacement complicated by iatrogenic left ventricular outflow obstruction and paravalvular leak: case report and review of literature

BackgroundLeft ventricular outflow tract (LVOT) obstruction and paravalvular leak (PVL) are relatively uncommon, but are serious complications of prosthetic valve replacement.Case presentationWe present a case that displays the unique therapeutic challenges of treating a patient who developed both LVOT obstruction and mitral PVL after undergoing surgical aortic and mitral valve replacement (MVR). We also describe the use of alcohol septal ablation and albumin-glutaraldehyde (BioGlue) for septal ablation to percutaneously treat the patient’s LVOT obstruction, followed by use of an Amplatzer vascular plug for percutaneous closure of an antero-medial mitral PVL associated with severe regurgitation.ConclusionPercutaneous interventional management of these entities may be considered as an initial therapeutic option, especially in high-risk patients with significant morbidity and mortality of repeat surgical operations.

A comparison of methods for determining the partition coefficient of gadolinium in the myocardium using T1 mapping

Late gadolinium enhancement can evaluate focal, but not diffuse myocardial fibrosis. T1-mapping techniques can quantify fibrosis by calculating the partition coefficient (λ) of gadolinium (Gd). One method (CI) calculates λ at equilibrium following a continuous infusion of Gd, while the other, early post-contrast method (EPC), determines λ from multiple post-contrast time points after Gd injection. The Modified Look-Locker Inversion Recovery (MOLLI) technique accurately performs T1 mapping, but may be limited in practice due to the long breathhold required. A shortened-MOLLI technique (Sh-MOLLI) has been described, which only allows a single heart beat for magnetization recovery.