Amresh Raina

Longitudinal Shortening Accounts for the Majority of Right Ventricular Contraction and Improves After Pulmonary Vasodilator Therapy in Normal Subjects and Patients With Pulmonary Arterial Hypertension

BACKGROUND The right ventricle has a unique contraction pattern, with a greater portion of the shortening occurring in the longitudinal plane. However, the relative contributions of longitudinal and transverse shortening to overall right ventricular (RV) function have not been quantified. We sought to quantify the proportions of longitudinal and transverse shortening to RV function in normal subjects and in patients with pulmonary arterial hypertension (PAH) at baseline and following PAH-specific therapy. METHODS The normal cohort comprised 90 subjects with normal clinical echocardiograms, whereas the PAH cohort included 36 patients, of whom 25 had echocardiograms before and after initiation of PAH-specific therapy. Assessment of RV function included tricuspid annular plane systolic excursion, RV fractional area change (RVFAC), and relative change in RV area in longitudinal and transverse planes. RESULTS Longitudinal fractional area change (LFAC) accounted for the majority of total RVFAC (77% ± 14%) in normal subjects. Among patients with PAH, longitudinal shortening still represented the majority of RVFAC, even though it was less than in normal subjects (63% ± 18%, P < .0001). Following PAH therapy, overall RV function improved (RVFAC, 30% ± 13% to 36% ± 9%; P = .026), solely because of an increase in longitudinal area change. As a result, the proportion of longitudinal shortening increased (LFAC, 58% ± 18% to 69% ± 17%; P = .002), whereas transverse shortening fell (transverse fractional area change, 42% ± 18% vs 31% ± 17%; P = .002). CONCLUSIONS Longitudinal shortening accounts for the majority of RV contraction in normal subjects and patients with PAH, although less so in PAH. Improved RV function following pulmonary vasodilator therapy occurs solely from improvements in longitudinal contraction, suggesting that longitudinal shortening may represent the afterload-responsive element of RV functional recovery.

Marked changes in right ventricular contractile pattern after cardiothoracic surgery: Implications for post-surgical assessment of right ventricular function

BACKGROUND Longitudinal shortening accounts for the majority of right ventricular (RV) contraction in normal hearts. This finding accounts for the correlation between longitudinal measures of RV contraction such as tricuspid annular plane systolic excursion (TAPSE) and global RV function. We hypothesized that, after cardiac surgery, there are major differences in the RV contractile pattern relative to normal hearts. METHODS We retrospectively studied 2 cardiac surgical cohorts who underwent cardiopulmonary bypass (CPB) with pericardial incision (OHT, n = 54; CABG, n = 23) and compared them with a lung transplant cohort (n = 25). We compared TAPSE, RV fractional area change (RVFAC) and relative change in RV transverse and longitudinal area in the surgical cohorts with data from normal subjects (n = 84). RESULTS RVFAC was lower in the surgical groups compared with the normal group, yet still in the normal range (37% to 42% vs 47%; p < 0.01). TAPSE was markedly lower in OHT (15 ± 3 mm) and CABG (16 ± 4 mm) than in normal (26 ± 4 mm) subjects (p < 0.01), as was the relative contribution of longitudinal area change (OHT group 51 ± 11%, CABG group 54 ± 13%, normal group 78 ± 14%; p < 0.01). The ratio of TAPSE to RVFAC was markedly lower in CABG (40 ± 14 mm/%FAC) and OHT (37 ± 10 mm/%FAC) patients than in normal (56 ± 14 mm/%FAC) subjects (p < 0.001). However, OLT patients had a higher TAPSE (18 ± 3 mm) than OHT (15 ± 3 mm) and CABG (16 ± 4 mm) patients (p < 0.01) and a higher relative contribution of longitudinal area change: OLT 67 ± 10%; OHT 51 ± 11%; and CABG 54 ± 13% (p < 0.01). CONCLUSIONS After cardiac surgery, the RV contractile pattern changes, with a relative loss of longitudinal shortening and gain in transverse shortening despite normal global RV function. These findings have major implications for quantitative assessment of RV function after cardiac surgery, suggesting that global measures of RV function assessment may be preferred in this setting and that lower normative ranges should be used when measurement of RV function is performed with longitudinal methods.

Inverted‐Takotsubo Pattern Cardiomyopathy Secondary to Pheochromocytoma: A Clinical Case and Literature Review

Takotsubo cardiomyopathy is an increasingly recognized clinical syndrome of transient left ventricular dysfunction, commonly with apical ballooning, in the context of physical or emotional stress. Recently, an inverted‐Takotsubo contractile pattern has been described with hypokinesis of the basal and mid‐ventricular segments and sparing of the apex. We report a case of a 30‐year‐old man presenting with transient left ventricular dysfunction in an inverted‐Takotsubo contractile pattern, associated with a newly discovered pheochromocytoma, and present a literature review of the inverted‐Takotsubo contractile pattern cardiomyopathy. Copyright

Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.

Pulmonary hypertension related to left heart disease: Insight from a wireless implantable hemodynamic monitor

BACKGROUND Pulmonary hypertension (PH) associated with left heart disease (World Health Organization [WHO] Group II) has previously been linked with significant morbidity and mortality. However, there are currently no approved therapies or hemodynamic monitoring systems to improve outcomes in WHO Group II PH. METHODS We conducted a retrospective analysis of the CHAMPION trial of an implantable hemodynamic monitor (IHM) in 550 New York Heart Association (NYHA) Functional Class III HF patients, regardless of left ventricular ejection fraction (LVEF) or heart failure (HF) etiology. We evaluated clinical variables, changes in medical therapy, HF hospitalization rates and survival in patients with and without WHO Group II PH. RESULTS Data were obtained for 314 patients (59%) who had WHO Group II PH. Patients without PH were at significantly lower risk for mortality than PH patients (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.19 to 0.52, p < 0.0001). PH patients had higher HF hospitalization rates than non-PH patients (0.77/year vs 0.37/year; HR 0.49, 95% CI 0.39 to 0.61, p < 0.001). In patients with and without PH, ongoing knowledge of hemodynamic data resulted in a reduction in HF hospitalization for PH patients (HR 0.64, 95% CI 0.51 to 0.81, p = 0.002) and for non-PH patients (HR 0.60, 95% CI 0.41 to 0.89, p = 0.01). Among PH patients, there was a reduction in the composite end-point of death and HF hospitalization with ongoing knowledge of hemodynamics (HR 0.74, 95% CI 0.55 to 0.99, p = 0.04), but no difference in survival (HR 0.78, 95% CI 0.50 to 1.22, p = 0.28). CONCLUSIONS WHO Group II PH is prevalent and identifies HF patients at risk for adverse outcomes. Ongoing knowledge of hemodynamic variables may allow for more effective treatment strategies to reduce the morbidity of this disease.

The impact of mitral regurgitation on patients undergoing catheter ablation of atrial fibrillation.

AIMS Mitral regurgitation (MR) causes left atrium (LA) enlargement and subsequent atrial fibrillation (AF). The presence of MR may increase recurrence rates after AF ablation. The purpose of this study was to determine the impact of MR on recurrence rates after catheter ablation of AF. METHODS AND RESULTS We compared 95 patients with moderate or greater baseline MR (defined by MR jet area to LA area ratio ≥ 0.2) and AF undergoing ablation to 95 randomly selected patients without significant MR undergoing AF ablation. Electrocardiographic recurrence at 1-year follow-up was the primary outcome. Patients in the MR cohort had mean MR/LA ratio 0.37 vs. 0.09 in controls (P< 0.0001). Mitral regurgitation patients had larger LA dimension (4.5 vs. 4.1 cm, P< 0.0001) and more persistent AF (71 vs. 28%, P< 0.0001). Mitral regurgitation patients had higher recurrence rates than controls (61 vs. 46%, P= 0.04). The degree of MR was higher in patients with recurrence (MR/LA ratio 0.25 vs. 0.20, P= 0.03), as was LA dimension (4.5 vs. 4.1 cm, P< 0.0001). In multivariate analyses, only LA size was an independent predictor of recurrence (odds ratio 2.9 per centimetre increase in LA dimension, P= 0.005). Fifty-five percent of MR patients had normal leaflet motion, with MR likely due to atrial remodelling secondary to AF. CONCLUSION Mitral regurgitation was associated with increased AF recurrence after AF ablation, but its impact was mediated by LA size. Left atrium size was the only independent predictor of AF recurrence. The high percentage of MR that was likely secondary to AF may have impacted our findings and deserves further study.

Role of Phosphodiesterase-5 Inhibitors in Heart Failure: Emerging Data and Concepts

Novel treatment of congestive heart failure (HF) involves utilizing unique pathways to improve upon contemporary therapies. Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Preclinical studies suggest a favorable myocardial effect of PDE5 inhibitors by blocking adrenergic, hypertrophic and pro-apoptotic signaling, thereby supporting their use in HF. The clinical benefits of acute and chronic PDE5 inhibition on lung diffusion capacity, exercise performance and ejection fraction in humans are emerging and appear promising. Larger, controlled trials are now on-going to assess the safety, efficacy and tolerability of PDE5 inhibitors on morbidity and mortality in patients with both systolic and diastolic heart failure. If the results of these trials are positive, a new avenue for the treatment of HF will open, which will help curtail the societal effects of this costly and morbid disease.

Limitations of right heart catheterization in the diagnosis and risk stratification of patients with pulmonary hypertension related to left heart disease: Insights from a wireless pulmonary artery pressure monitoring system

BACKGROUND Although right heart catheterization (RHC) remains the gold standard for assessment of hemodynamics in patients with known or suspected pulmonary hypertension (PH), there are significant limitations to this type of assessment. The current study evaluates the limitations of RHC in the diagnosis of left heart-related PH (World Health Organization group II) among patients enrolled in the CHAMPION trial and discusses insights into patient risk from home implantable hemodynamic monitor (IHM) data that were not identified at the time of the RHC procedure. METHODS The CHAMPION trial enrolled 550 New York Heart Association functional class III patients who had been hospitalized for heart failure (HF) in the previous year, regardless of left ventricular ejection fraction or etiology. Hemodynamic data obtained during baseline RHC were compared with IHM data obtained during the first week of home readings. HF hospitalization rates and mortality were analyzed to assess patient risk. RESULTS The study population for this retrospective analysis comprised 537 patients with available IHM data. For 320 patients in the PHRHC group, home IHM data confirmed the RHC findings with similar mean pulmonary artery pressures obtained from both methods (36 mm Hg vs 36 mm Hg, p = 0.5066). However, of the 217 patients in the No PHRHC group, 106 patients (48.8%) exhibited PH based on the home IHM data (PHIHM group). The remaining 111 patients (51.2%) in the No PHRHC group had no evidence of PH on the IHM data (No PHIHM group). Patients in the No PHRHC/PHIHM group had significantly higher mean PA pressures on IHM than patients in the No PHRHC/No PHIHM group (31 mm Hg vs 18 mm Hg, p < 0.0001). Patients in the No PHRHC/No PHIHM group had significantly lower HF hospitalization rates than patients in the No PHRHC/PHIHM group (0.25 vs 0.49, incidence rate ratio = 0.51, 95% confidence interval = 0.33-0.77, p = 0.0007). CONCLUSIONS Using only RHC, World Health Organization group II PH may be significantly under-diagnosed. In patients with left-sided HF and resting mean PA pressure ≤25 mm Hg during RHC, more frequent PA pressure monitoring using an IHM device can provide additional data for improved diagnosis and patient risk stratification compared with a single RHC alone.

Comparison of Invasive and Noninvasive Assessment of Aortic Stenosis Severity in the Elderly

Background— Aortic valve area (AVA) in aortic stenosis (AS) can be assessed noninvasively or invasively, typically with similar results. These techniques have not been validated in elderly patients, where common assumptions make them most prone to error. Accurate assessment of AVA is crucial to determine which patients are appropriate candidates for aortic valve replacement. Methods and Results— Fifty elderly patients (mean 86 years, 46% female) referred for cardiac catheterization to evaluate AS also underwent transthoracic echocardiography within 24 hours. To minimize assumptions all patients had 3-dimensional echocardiography (Echo-3D), and at catheterization using directly measured oxygen consumption (Cath-mVo2) and thermodilution cardiac output (Cath-TD). Correlation between Cath-mVo2 and Echo-3D AVA was poor (r=0.41). Cath-TD AVA had a moderate correlation with Echo-3D AVA (r=0.59). Cath-mVo2 (AVA=0.69 cm2) and Cath-TD (AVA=0.66 cm2) underestimated AVA compared with Echo-3D (AVA=0.76 cm2; P=0.08 for comparison with Cath-mVo2; P=0.001 for Cath-TD). Compared with Echo-3D, the sensitivity and specificity for determining critical disease (AVA <0.8 cm2) were 81% and 42% for Cath-mVo2, and 97% and 53% for Cath-TD. The only independent predictor of the difference between noninvasive and invasive AVA was stroke volume index (P<0.01). Resistance, a less flow-dependent measure, showed a stronger correlation between Echo-3D and Cath-mVo2 (r=0.69), and Echo-3D and Cath-TD (r=0.77). Conclusions— Standard techniques of AVA assessment for AS show poor correlation in elderly patients, with frequent misclassification of critical AS. Less flow-dependent measures, such as resistance, should be considered to ensure that only appropriate patients are treated with aortic valve replacement.

The pathophysiology of endothelin in complications after solid organ transplantation: a potential novel therapeutic role for endothelin receptor antagonists.

Although short-term allograft survival after solid organ transplantation has improved during the past two decades, improvement in long-term graft survival has been less pronounced. Common complications after transplantation include chronic allograft rejection, nephrotoxicity from calcineurin inhibitors (CNIs), and systemic hypertension, which all impact posttransplantation morbidity and mortality. Endothelin (ET)-1, a potent endogenous vasoconstrictor, inducer of fibrosis, and vascular smooth muscle cell proliferation, may play a key role in both the development of CNI-induced nephrotoxicity and endothelial vasculopathy in chronic allograft rejection. ET-1 levels increase after isograft implantation, and ET-1 plays a key role in CNI-induced renal vasoconstriction, sodium retention, and hypertension. Preclinical studies have demonstrated that endothelin receptor antagonists (ERAs) can reduce or prevent CNI-induced hypertension after renal transplantation. In addition, ERAs can ameliorate CNI-induced renal vasoconstriction and improve proteinuria and preserve renal function in animal models of renal transplantation. ET-1 may also play a significant role in cardiac allograft vasculopathy, and in animal models, ERAs improve pulmonary function and ischemic-reperfusion injury in lung transplantation and hepatic function and structure in liver transplantation. Emerging pharmacokinetic data suggest that the selective ERA ambrisentan may be used safely in conjunction with the most commonly used immunosuppressive agents tacrolimus and mycophenolate, albeit with appropriate dose adjustment. The weight of available evidence pointing toward a potential beneficial role of ERAs in ameliorating common complications after solid organ transplantation must be balanced with potential toxicities of ERAs but suggests that a randomized clinical trial of ERAs in transplant patients is warranted.